Myelin basic protein. Markers of disorders of the nervous system What can affect the result

Table of contents

1. neurospecific proteins

myelin basic protein

Neuron-specific enolase

Neurotropin-3 and Neurotropin-4/5

brain-derived neurotrophic factor

ciliary neurotrophic factor

Phosphorylated neurofilament H

Pigment factor of epithelial origin

Glial fibrillar acidic protein

2. Alzheimer's disease

Glycosylation end product receptor

Nikastrin

. β-amyloid

Chlamydia pneumoniae

Melatonin and melatonin sulfate

Serotonin

Diagnostic significance of determining autoantibodies to glycolipids in peripheral NP

Antibodies to myelin-associated glycoprotein

Antibodies to sulfated glucuronate paragloboside

Antibodies to gangliosides

Antibodies to ganglioside M1

Antibodies to ganglioside GD1b

Antibodies to ganglioside GQ1b

Antibodies to interferon β

Antibodies to sphingomyelin

Anti-laminin β antibodies

Anticochlear antibodies

Anti-neuronal autoantibodies

Antibodies to ribosomal P proteins and RNA

Section Abbreviations

AD - Alzheimer's disease

DNP - demyelinating neuropathy

NP - neuropathy

NSP - neurospecific proteins

PNS - peripheral nervous system

CSF - cerebrospinal fluid

CNS - central nervous system

NGF - nerve growth factor

Neuroimaging and electrophysiological examination methods are traditional for diagnosing conditions associated with brain tissue damage. Recently, more and more attention has been attracted by laboratory diagnostics, including the determination of neurospecific proteins (NSPs) - biologically active molecules specific to nerve tissues and performing functions characteristic of the nervous system. Over the past 30 years, more than 60 different NBPs of the brain have been characterized. They can be classified according to the localization-structural principle (neuronal, glial; membrane-associated and cytoplasmic, etc.), according to their functional role, and they can also distinguish a subgroup of NSPs that are present in normal and pathological conditions. Determining the level of NSB contributes to early diagnosis, because. significant changes in their concentration often occur earlier than the damage that can be detected by instrumental examination methods. In addition, they allow to assess the prognosis of the course and outcome of the disease, to monitor the treatment of the patient.

neurospecific proteins

Myelin basic protein (MBP)

MVR is released into the cerebrospinal fluid (CSF) with any damage to the nervous tissue. The level of MVR increases with CNS injuries, tumors, multiple sclerosis, subacute sclerosing panencephalitis, viral encephalitis, and other neurological disorders. Also, the level of MBP rises within a few days after a stroke and reflects the destruction of the myelin sheaths. It is assumed that the MVR secreted into the CSF is not identical to that found in the tissue.

Neuron-specific enolase (NSE)

NSE is a neurospecific marker. Refers to intracellular enzymes of the CNS, which allows the use of NSE to determine postischemic brain damage. However, NSE can also increase in some other neurological processes (epilepsy, subarachnoid hemorrhage). It is also a marker of small cell lung cancer, neuroblastoma.

S-100 is a specific astrocytic glial protein capable of binding calcium. The protein got its name due to the property to remain in a dissolved state in a saturated solution of ammonium sulfate. The S-100 protein family consists of 18 tissue-specific monomers. Two of the monomers, α and β, form homo- and heterodimers, which are present in high concentration in the cells of the nervous system. S-100(ββ) is present in high concentrations in glial and Schwann cells, the S100(αβ) heterodimer is found in glial cells, and the S-100(αα) homodimer is found in striated muscles, liver, and kidneys. S-100 is metabolized by the kidneys and has a half-life of 2 hours. Astroglial cells are the most numerous cells in brain tissue. They form a three-dimensional network, which is the supporting framework for neurons. An increase in the concentration of S-100(αβ) and S-100(ββ) in CSF and plasma is a marker of brain damage. In patients with brain damage, when measured early, the S-100B content reflects the degree of brain damage. S-100 studies are useful both for monitoring and for determining the prognosis of the course of the disease.

Subarachnoid hemorrhage leads to a significant increase in the level of S-100 in the CSF. It should be noted that the concentration of protein in plasma remains low. The concentration of S-100 is significantly increased in plasma in patients operated on under cardiopulmonary bypass. The peak concentration occurs at the end of the extracorporeal circulation and then decreases in uncomplicated cases. A slowdown in the decrease in the concentration of S-100 in a patient in the postoperative period indicates the presence of complications and damage to brain cells. Early determination and monitoring of S-100 levels, as well as simultaneous S-100 and NSE studies, allow detection and confirmation of brain damage at an early stage, when successful treatment is possible. The S-100 test can also be used to predict neurological complications when examining patients with cardiac arrest.

An increase in S-100 in blood serum and CSF in cases of cerebrovascular accident is due to the activation of microglia. It was shown that in the early phase of cerebral infarction, microglial cells in the peri-infarct zone express S-100 and actively proliferate, with proteins being expressed no more than three days after infarction. This suggests that the activation of a constant population of microglia is an early response of brain tissue to ischemia and can be used as an early marker of damage.

The results of the S-100 study can be used to predict the possible development of various symptoms in traumatic brain injuries, conditions after bruises and concussions of the brain. It should be borne in mind that the concentration of S-100 protein increases significantly with age, and in men to a greater extent than in women.

S-100 is one of the earliest NSBs in the developing brain. It is found already at 3 months of the prenatal period in the pons, midbrain, cerebellum and occipital lobe, and by 6 months protein synthesis is observed in the frontal cortex. The functions of the CNS, in which S-100 is involved, begin to appear at 12-15 weeks of embryogenesis, and by the time of birth they are already well formed. A number of studies show the involvement of this protein in the regulation of learning and memory.

The S-100 protein increases during and after the reversible deterioration of the intrauterine state during the development of hypoxia. Its concentration in various biological fluids rises 48-72 hours before any standard procedure reflects cerebral impairment or fetal death. The high significance of the determination of S-100B in the amniotic fluid for the prediction of intrauterine fetal death was shown (Fig.): at the level of cut-o ff 1.19 µg/l test sensitivity is 90.9%, specificity is ~100%.

Cord blood S-100B levels can be used to assess intrauterine growth retardation (IUGR) (Fig.).

Neonates show a strong correlation between S-100 levels and severity of intraventricular hemorrhage (IVH) (Fig.)

The level of S-100B in the first 72 hours of life in full-term newborns with birth asphyxia is a reliable marker for predicting the development and severity of cerebral disorders.

S-100 (αβ+ββ) can be defined as an additional diagnostic and prognostic marker in malignant melanoma.

Neurotropin-3 (NT3) and Neurotropin-4/5 (NT4/5)

The family of neurotropins includes: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT3 and NT4/5. They support different populations of neurons in the CNS and PNS. NTs are secreted proteins found in the bloodstream that are capable of signaling individual cells for survival, differentiation, or growth. NTs act by preventing the initiation of apoptosis in the neuron. They also induce the differentiation of progenitor cells, the formation of neurons. NT play an important role in the functioning of the nervous system, in the regeneration of damaged neuronal structures.

Although the vast majority of neurons in the mammalian brain are formed during embryonic development, the adult brain partially retains the ability to neurogenesis - the formation of new neurons from neuronal stem cells. NT controls and stimulates this process. The trophic (ensuring survival) and tropic (direction of axon growth) properties of NT serve as the basis for their possible use in the treatment of various types of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, as well as peripheral neuropathies of various origins.

NT3 is a growth factor with m.m. 13.6 kDa (m.m. of the active form-dimer - 27.2 kDa). NT3 plays a role in the development of the sympathetic nervous system. In mice, elevated levels of NT3 have been found in sympathetic ganglia and organs during hyperinnervation and spontaneous hypertension. In asthmatic patients, corticosteroids increase serum NT3 levels. The concentration of NT3 in the frontal and parietal areas of the cortex is significantly reduced in patients with schizophrenia. NT3 is able to stimulate the largest number of neuron populations, since it activates two of the three NT tyrosine kinase receptors (TrkC and TrkB).

NT4/5 prevents the death of motor neurons in the perinatal and postnatal periods. The impact of NT4 / 5 is carried out mainly through the TrkB tyrosine kinase receptor.

Brain-derived neurotrophic factor (BDNF)

The mature mammalian BDNF molecule has a m.m. 13 kDa and consists of 119 amino acid residues. BDNF is 52% identical in amino acid composition to NGF. It exists in solution as a homodimer. BDNF is expressed in fibroblasts, astrocytes, neurons of various phenotypes and localizations, megakaryocytes/platelets, Schwann cells (in areas of injury) and, possibly, in smooth muscle cells. BDNF is found in plasma in amounts on the order of pg/ml, while in serum it is present in amounts on the order of ng/ml. The difference is due to the release of BDNF during platelet degranulation and blood clotting. The identity of the BDNF structure in different mammals potentially allows the use of this test system for different animal species.

At least 2 types of BDNF receptors are known, the first being low-affinity NGF receptors with m.m. 75 kDa (LNGFR), the second - high-affinity tropomyosin kinase-B receptors with 145 kDa m.m. (TrkB). It is known that LNGFR can enhance signaling along certain pathways. The biological significance of activation of these pathways is poorly understood. LNGFRs may be involved in the migration of Schwann cells to the site of injury and/or modulate TrkB activity on cells expressing both receptors simultaneously. TrkB has the ability to bind NT3 and 4. It is believed that TrkB receptors require their homodimerization to function, while there are data on the formation of functional heterodimers of TrkB and TrkC receptor molecules on cells expressing both of these receptors simultaneously. These cells include granular neurons of the cerebellum and cells of the dental nucleus of the hippocampus. There is evidence of TrkB expression on motor neurons of the spinal cord, pyramidal cells of the hippocampus, almost all cells of the developing brain, as well as on thymocytes, which indicates the role of BDNF in lymphopoiesis.

The functional activity of BDNF is quite high. During development, it is involved in neuronal differentiation, maturation, survival, and synapse formation. In the adult body, the main function of BDNF is neuroprotection, protecting brain neurons from ischemic attacks and motor neurons from death induced by axonal excision.

Ciliary neurotrophic factor (CNTF)

Human CNTF is a single chain polypeptide of 200 amino acid residues with m.m. 22.7 kDa. The molecule is highly conserved across species. Comparison of the amino acid sequences of human, rat, and rabbit CNTF showed 83% and 87% homology, respectively. CNTF is localized in Schwann cells and type 1 astrocytes.

CNTF belongs to a limited family of neuropoietic cytokines, including leukemia inhibitory factor (LIF) and oncostatin M (OSM). CNTF is regarded as a key differentiation factor for developing neurons and glial cells. CNTF provides trophism and is involved in the protection of damaged or axonotomized neurons. In particular, the death of motor neurons after axotomy of the rat facial nerve was prevented by applying CNTF to the proximal axonal segment. CNTF has demonstrated in vitro induction of cholinergic properties in adrenergic sympathetic motor neurons. This influence included the expression of acetylcholine as a neurotransmitter and the synthesis of substance P (SP) and vasoactive intestinal peptide (VIP) as acetylcholine-associated neuropeptides. The effect of CNTF on non-autonomous sensory neurons is less well understood. Dorsal root ganglion cells were found to increase SP expression in vivo, while SP and VIP expression did not increase in response to CNTF in vitro. In addition, CNTF is thought to be involved in glial differentiation. Other effects of CNTF include: promoting embryonic stem cell pluripotency, inducing survival and differentiation of adrenal chromaffin cells, and, like IL-6, inducing fever after intravenous injections. Interest in the study of CNTF is due to its property to promote the survival of neurons.

Phosphorylated neurofilament H (pNF-H)

pNF-H is a sensitive marker of axon damage. Neurofilaments make up the main part of the cytoskeleton of neurons. The three main neurofilament proteins are NF-L, -M and -H. Their concentration is especially high in axons. The NF-H protein has some unique properties. In axonal neurofilaments, the serine residues of this protein contained in the lysine-serine-proline repeats are highly phosphorylated. Phosphorylated forms of NF-H (pNF-H) are resistant to proteases after exit from damaged axons. Therefore, detection of this protein in CSF or blood can provide information on the extent of axonal damage.

pNF-H is only detectable in serum samples in the presence of spinal cord or brain injury. pNF-H concentrations can reach high levels (>250 ng/mL) and return to zero levels weeks after injury. Since pNF-H is expressed only in axons, determination of its content is a convenient and sensitive biomarker for assessing axonal damage. It has been shown that pNF-H can be detected in the plasma of people suffering from optic neuritis or in the CSF of patients with malignant brain tumors or stroke.

Pigment factor of epithelial origin (PEDF)

PEDF is a glycoprotein with m.m. ~50 kDa, which has many biological functions. It is a neuroprotective and neurotrophic factor that affects various types of neurons. It has been shown that PEDF is a strong activator of neuronal differentiation of human retinoblastoma cells. It has been shown in birds and mice to promote survival and differentiation of developing spinal cord motor neurons, support normal amphibian photoreceptor neuron development, and opsin expression in the absence of retinal pigment epithelial (RPE) cells.

In rats, PEDF is a survival factor for cerebellar granular neurons, protecting them from apoptosis and glutamate neurotoxicity. It also protects motor neurons and developing hippocampal neurons from glutamate-induced degeneration. It has been shown in cell cultures that it protects retinal neurons from peroxide-induced death.

Glial fibrillar acidic protein (GFAP)

GFAP is a member of the cytoskeletal protein family and is the major 8-9 nm intermediate filament in mature CNS astrocytes. GFAP is a monomeric molecule with m.m. 40-53 kDa and an isoelectric point of 5.75.8. It is a highly specific brain protein that is not found outside the CNS. GFAP has been shown to be released into the bloodstream very rapidly after traumatic brain injury (may serve as a marker of injury severity and predictor of outcome), but GFAP is not released in multiple trauma without brain injury. In the CNS, after injury (whether as a result of injury, disease, genetic disorder, or chemical stroke), astrocytes respond with astrogliosis as a result of typical behavior. Astrogliosis is characterized by rapid synthesis of GFAP. It is known that the level of GFAP usually increases with age. Due to its high specificity and early release from the CNS after traumatic brain injury, GFAP may prove to be a very useful marker for early diagnosis.

Alzheimer's disease

Alzheimer's disease (AD) is a progressive senile dementia that affects about half of the population of people over 85 years of age. The hallmarks of this disease are memory loss and other behavioral abnormalities that correlate with loss of neurons primarily in the cerebral cortex and hippocampus. AD is characterized by the presence of extracellular plaques and intracellular neurofibrillary tangles in the brain tissues.

Glycosylation End-Product Receptor (RAGE)

RAGE is a type I multiligand transmembrane glycoprotein belonging to the immunoglobulin (Ig) superfamily. RAGE has been suggested to be involved in various pathological processes, including diabetes mellitus, Alzheimer's disease (AD), systemic amyloidosis, and tumor growth. RAGE may be involved in physiological functions such as neuronal growth, survival and regeneration, and pro-inflammatory responses. High expression of RAGE is observed during development, especially in the CNS. RAGE ligands include glycosylation end products (AGEs), amyloid-β (Aβ), HMG-1 (also known as amphotericin), and some S-100 family proteins. Aβ is the main component of senile or amyloid plaques, one of the key neuromorphological features of AD. RAGE is a receptor for the β-fold structures characteristic of amyloid, and a localized increase in its level near Aβ in the AD brain has been found. The interaction of Aβ with RAGE expressed on endothelial cells, neurons, and microglia leads to the formation of reactive oxygen species and the production of pro-inflammatory factors, which is a proposed mechanism underlying the neurodegenerative process in AD. Recent studies have shown the possibility of RAGE involvement in Aβ transport across the blood-brain barrier and its accumulation in the CNS.

It has been shown that the interaction of RAGE with its HMG-1 ligand regulates cell motility. For example, HMG-1/RAGE is able to stimulate axon growth in neuroblastoma cells. Blocking HMG-1/RAGE binding suppresses tumor growth and metastasis in animal experiments. In addition, RAGE and S-100 concentrations have been shown to be elevated in multiple sclerosis and in experimental autoimmune encephalomyelitis (EAE).

Nikastrin

Nikastrin is a 709 amino acid type I transmembrane glycoprotein that has recently been described as a key component of an AD-associated multiprotein complex formed with proteases (presenilin-1 and -2). The formation of this complex is the final step in the formation of the neurotoxic β-amyloid peptide (also known as amyloid), which can be found in brain plaques in patients with familial AD. The amyloid protein is formed from the membrane-bound precursor protein β-amyloid (βAPP) in two steps. First, β-APP is cleaved by the protease β-secretase (BACE-2) and then the amyloid protein is released during subsequent γ-secretase processing. Presenilins-1 and -2 have been shown to have protease catalytic activity, which is required for the formation of the neurotoxic β-amyloid peptide. It is known that nikastrin binds to β-APP and is able to modulate the formation of β-amyloid peptide. This indicates a direct role of nicastrin in the pathogenesis of AD and allows us to consider it as a potential target for therapeutic intervention.

β-amyloid (Ab40, Ab42)

The main protein component of plaques in AD is β-amyloid, a peptide consisting of 40-43 amino acid residues, cleaved from the precursor protein (APP) by the enzymes β-secretase and, possibly, γ-secretase.

Increased secretion of peptides with a higher m.m. (Aβ42 or Aβ43) occurs with certain genetic mutations, with the expression of some ApoE alleles, or with the participation of other, as yet unknown, factors. Not only the proteolytic cleavage of APP and the subsequent appearance of Aβ may be important factors in the progression of AD, but Aβ aggregation may also be critical in the development of this disease, leading to the development of the dense plaques that are found in the brains of AD patients. It has been shown that Aβ42 or Aβ43 tend to aggregate to a much greater extent than peptides with lower MW. It has been shown that an increase in the concentration of Aβ42/Aβ43 leads to an abnormal accumulation of Aβ and is associated with neurotoxicity in brain tissues in AD. For patients with AD, a decrease in the level of Aβ42 in the CSF is a prognostic factor. Determination of the Aβ peptide can also be used to identify human Aβ in mice in an AD model. Determination of various peptide fragments to study the cellular response to exposure to Aβ peptides can help understand the early events that lead to neuronal cell death. Aβ peptides can activate various signal transduction pathways. For example, it has recently been shown that fibrillar Aβ activates the tyrosine kinases Lyn and Syk, thus initiating a signaling cascade that activates the proline-rich/calcium-dependent tyrosine kinase Pyk2.

Given that Aβ peptides tend to aggregate, the quality of diagnostic kits may vary from manufacturer to manufacturer, lot to lot. BioS ource International has developed highly sensitive and highly specific ELISA kits for the quantitative determination of Aβ 1-40 or 42.

Chlamydia pneumoniae

Using the PCR method in independent studies, it was shown that 89-92% of a patient with BA had a positive reaction to the Ch antigen. pneumoniae (brain). Ch antigen. pneumoniae has been identified in extracellular plaques in the brains of patients with AD, in contrast to the brains of patients with other brain lesions leading to dementia.

Ch. pneumoniae infects monocytes, which leads to an increase in their migration through the hemencephalotic barrier. Ch. pneumoniae results in dysregulation of β-cathepsin, N-cadherin, VE-cadherin, and other intercellular adhesion molecules. When determining antibodies in the sera of patients with AD and Parkinson's disease using ELISA, the following results were obtained:

Alzheimer's disease: IgA - 45%, IgG - 36% positive;

Parkinson's disease: IgA - 35%, IgG - 83% positive results.

Alzheimer's disease: the role of oxidative stress

It has been shown that oxidative stress (OS) plays an important role in the pathogenesis of AD. BA develops in presenile or old age in parallel with OS strengthening. The main signs of AD in patients in the late stages are neurofibrillary tangles (NFTs) and β-amyloid (senile) plaques in the cerebral cortex. Many studies have shown that in the early stages in patients with AD, various signs of OS can be observed - oxidative damage to nucleic acids, proteins and lipids, the presence of various biomarkers of OS has also been shown (Fig. Numerous studies are currently underway on new therapeutic approaches to prevent or slow the development of this disease, based on protection against oxidative stress.

Markers of the functional state of the epiphysis

The pineal gland is part of the central system of neurohumoral regulation of the body. The pineal gland plays a leading role in transmitting information to all life-supporting systems of the body about the change of day and night, as well as in organizing seasonal and circadian rhythms and regulating reproductive functions. To assess the functional state of the pineal gland, it is currently necessary to determine melatonin and serotonin in the blood and metabolic products of melatonin (melatonin sulfate) in the urine.

Melatonin and melatonin sulfate

Melatonin, or N-acetyl-5-methoxy-tryptamine, is the main hormone of the pineal gland. It is synthesized in the pineal gland from an intermediate metabolite of serotonin - N-acetylserotonin. The level of melatonin in the blood has significant individual fluctuations, the maximum values ​​of melatonin in the blood are observed between midnight and 4 o'clock in the morning. The regulation of melatonin secretion is under the control of the sympathetic nervous system, which exerts its regulatory influence through norepinephrine. The half-life of melatonin is 45 minutes. This means that for research purposes, blood samples must be collected at short intervals in order to determine the period in melatonin production. In addition, disturbing the patient's sleep during the night for the purpose of sample collection may affect blood melatonin levels. These problems can be avoided by determining the levels of melatonin metabolites: melatonin sulfate (6-sulfatokymelatonin) and 6-hydroxyglucuronide in the urine. 80-90% of melatonin is secreted into the urine as sulfate. Urinary melatonin sulfate concentration correlates well with total blood melatonin levels during the sampling period.

Currently, the physiological and pathophysiological role of melatonin is being actively studied. An abnormal level of melatonin in the blood corresponds to sleep disorders, depression, schizophrenia, hypothalamic amenorrhea, and some types of malignant neoplasms. Premature puberty may be due to the presence of a tumor in the epiphysis. If the tumor develops from enzymatic elements of the parenchyma, then the phenomena of hyperpinealism or dispinealism predominate. Insufficiency of melatonin secretion by the pineal gland leads to increased production of FSH and, consequently, to the persistence of the follicle, polycystic ovaries, and general hyperestrogenism. Against this background, uterine fibromatosis, dysfunctional uterine bleeding can develop. Hyperfunction of the pineal gland, on the contrary, induces hypoestrogenism, sexual frigidity. An increase in the level of melatonin in the blood and its excretion in the urine is observed in patients with manic states.

Violation of melatonin production, both quantitatively and its rhythm, is the starting point, leading at the initial stages to desynchronosis, followed by the occurrence of organic pathology. Therefore, the melatonin disruption itself can be the cause of various diseases. Data have been obtained that allow melatonin to be considered one of the most powerful endogenous antioxidants. Moreover, unlike most other intracellular antioxidants, which are localized predominantly in certain cellular structures, the presence of melatonin and, consequently, its antioxidant activity, is determined in all cellular structures, including the nucleus.

Serotonin

Serotonin is an intermediate product of tryptophan metabolism, which is formed mainly in enterochromaffin cells of the small intestine, in serotonergic neurons of the brain, and in blood platelets. Almost all serotonin in the circulating blood is concentrated in platelets. Changes in the concentration of circulating serotonin are observed in chronic headache, schizophrenia, hypertension, Huntington's disease, Duchenne muscular dystrophy and early stage of acute appendicitis. Determination of serum serotonin levels is of great clinical importance for the diagnostic evaluation of the carcinoid syndrome.

Autoimmune diseases of the nervous system

Polyneuropathies (neuropathy, NP) can be classified by etiology (vascular, allergic, toxic, metabolic, etc.) or by clinical manifestations (sensory, motor, sensorimotor, mononeuropathies, etc.). Common signs of peripheral neuropathy are weakness and loss of sensation or pain in the extremities. Accurate diagnosis of peripheral neuropathies requires a collaborative analysis of clinical signs, medical history, and laboratory tests that can allow identification, confirmation, classification, and monitoring of the disease.

In recent years, many glycoconjugates have been considered as putative targets for various NPs. Increasingly, NP is characterized not only by clinical and electrophysiological criteria, but also immunochemically, depending on the type of antigen recognized by antiglycolipid antibodies. Glycoconjugates include both glycoproteins (eg MAG) and glycolipids (eg gangliosides, SGPG, sulfatides or sulfolipids). They are found in all tissues and are components of the myelin sheath of nerve fibers. Among the wide variety of glycolipids to date, three have shown important clinical significance in the diagnosis of NP and the choice of treatment (Fig.). A significant correlation was found between individual clinical features and types of antibodies to various glycoconjugates present in serum.

The main targets for autoantibodies in autoimmune peripheral NP are sulfated glucuronate paragloboside (SGPG) and ganglioside GM1. The former is a target mainly in demyelinating NP associated with monoclonal IgM gammopathy. The latter is the predominant target in motor NP, mainly in multifocal motor neuropathy. Anti-GQlb IgG antibodies are characteristic of a subgroup of patients with Miller-Fischer syndrome, (a variant of Guillain-Barré syndrome). Elucidation of the epitope structure may also be important in determining the pathological role of antibodies.

In many cases, separate definitions of IgG and IgM autoantibody classes are of high importance, since IgG class antibodies are more characteristic of acute neuropathies, and IgM antibodies are more often present in chronic conditions.

Structure and localization of the three major glycoconjugate antigens on peripheral nerves A. Myelin-associated glycoprotein containing five extracellular Ig-like domains accessible to autoantibodies, a transmembrane domain, and a cytoplasmic tail. B. Sulfated glycolipids and ganglioside GM1, whose oligosaccharide chains are located close to the lipid bilayer of the myelin membrane.

Diagnostic significance of determining autoantibodies to glycolipids in peripheral NP:

They are an important addition to electrodiagnostic methods for identifying various subgroups of autoimmune NP: various neurological symptoms are determined by the profile of antiglycolipid antibodies.

The possibility of accurate differential diagnosis of NP, which are based on immunological disorders (for example, NP in monoclonal gammopathies, multifocal motor NP or Guillain-Barré syndrome).

Control of therapy of NP associated with monoclonal gammopathy.

Conducting scientific research in the field of neuroimmunology.

Antibodies to myelin-associated glycoprotein (anti-MAG)

MAG belongs to cell adhesion molecules and is expressed on oligodendrogliocytes and Schwann cells. It is a mediator of interactions of oligodendrogliocytes with each other and with neurons. During axon myelination, it is also found on their outer surfaces and adjacent surfaces of myelin-forming cells. More than 50% of patients with peripheral NP and IgM monoclonal gammopathy have IgM monoclonal antibodies that bind to MAG.

Determination of anti-MAG antibodies is essential for differentiating IgM-associated NP from other commonly occurring acquired polyneuropathies such as CIDP (chronic inflammatory demyelinating NP). Both disorders can slowly progress and appear on morphological and electrophysiological studies mainly as demyelinating NP (DNP). In addition, in these diseases, the concentration of protein in the CSF is increased, and this indicator can be used to judge the effectiveness of the immunosuppressive therapy.

Table. Peripheral neuropathies associated with specific autoantibodies

Clinical Syndromes/Specific Antibodies	MAG SGPG	GM1	asialo- GM1	GM2	GD1a	GD1b	GQ1b
Guillain-Barré Syndrome (GBS)		+++ IgG IgG>IgM 20-30%	(+)	+ IgM 6%	+ IgG 5%	+ IgG 2%
GBS options: AMSAN and AMSAN		+++	+		+++	+
GBS with ophthalmoplegia							++ IgG
GBS with ataxic syndrome						++
GBS as a complication of CMV infection				+ IgM			+++ IgG >90%
Miller-Fisher Syndrome
Multifocal motor neuropathy (MMN)		++ IgM 20-80%	(+)			+
Defeat syndrome lower motor neuron		(+) IgM 5%	+
neuropathy, associated with anti-MAG/SGPG IgM monoclo- gammopathy	+++ m-IgM 50%
motor neuropathy, IgM-associated monoclonal gammopathy		+++ m-IgM 10%				+++
Sensory ataxic neuropathy and CANOMAD syndrome						+++ m-IgM	+++ m-IgM
Chronic inflammatory demyelinating polyneuropathy (CIDP)	++ m-IgM	+

Symbols:

Determination of the level of antibody titer to glycolipids: (+) - weakly positive, + - moderately positive, ++ - positive, +++ - highly positive;

. [%] - the percentage of patients who have detected autoantibodies to glycolipids.

. The blue color of the cell indicates the IgG class or the predominance of IgG anti-glycolipid antibodies; orange color belongs to the IgM class.

Usage example 1: antibodies to GM1 in GBS are often detected in high titers, with the IgG isotype predominating. GM1 IgG are detected in 20-30% of patients.

Usage example 2: monoclonal antibodies IgM to GD1b are usually present in high titers in sensory ataxic neuropathy and CANOMAD syndrome.

Anti-sulfated glucuronate paragloboside (SGPG) antibodies

The oligosaccharide sequence of SGPG with glucuronyl sulfate (i.e., the HNK-1 epitope) is shared by the sulfated glucuronate paragloboside and its derivatives and proteins, mainly myelin-associated proteins, myelin-oligodendrocyte glycoprotein (MOG) in the CNS, and myelin peripheral protein (PMP22) in PNS, acetylcholinesterase isoforms, and subgroups of several adhesion molecules such as the neural cell adhesion molecule (NCAM). It is believed that, regardless of protein specificity, anti-SGPG IgM is almost always detected in biological samples in NPD and in some motor neuron diseases. It has been shown that both anti-MAG and anti-SGPG antibodies are detected in typical sensory DNP, while only monoclonal IgM-anti-SGPG antibodies are present in axonal NPD. In patients, there is a relationship between the titer of antibodies to the HNK-1 epitope and the degree of demyelination.

Antibodies to gangliosides (GanglioCombi)

The GanglioCombi kit is designed to screen in human serum for autoantibodies directed against the gangliosides asialo-GM1, -GM2, -GD1a, -GD1b and -GQ1b. Gangliosides form a family of acidic sialylated glycolipids composed of carbohydrate and lipid components. They are mainly found on the outer surface of the plasma membrane. The external arrangement of carbohydrate residues suggests that they serve as antigenic targets in autoimmune neurological disorders. Antibodies binding to carbohydrate antigens have been found in various peripheral NPs. There is a significant heterogeneity in the expression of gangliosides in the tissues of the PNS. GM1 and GD1 are mainly present on the motor nerves, GQ1b are found in increased amounts in the motor cranial nerves of the muscles of the eyeball. High expression of GD1b is observed in sensory nerves. A clear correlation was shown between the content of specific anti-ganglioside antibodies and various variants of Guillain-Barré syndrome (GBS). Patients with elevated levels of antiganglioside antibodies have a good therapeutic prognosis.

Antibodies to ganglioside M1 (anti-GM1 autoantibodies)

Multifocal motor neuropathy (MMN) is characterized by blockage of impulse conduction along the axons of the lower motor neurons. Clinical features make it difficult to differentiate between MMN and amyotrophic lateral sclerosis (ALS). Since MMN, unlike ALS, is a treatable disease, it is extremely important to differentiate these diseases at an early stage. While high titers of anti-GM1 antibodies are virtually undetectable in ALS patients, more than 80% of MMN patients have these antibodies. In MMN, simultaneous determination of IgG and IgM isotypes of anti-GM1 antibodies is recommended. Anti-GM1 antibodies occur in approximately 5% of healthy individuals, especially the elderly, and their production may be a manifestation of normal immune system activity. The detection of anti-GM1 antibodies is used to monitor the dynamics of seroconversion and the effectiveness of MMN therapy to prevent possible recurrence of the disease, as well as to confirm the diagnosis in all cases of polyneuropathies of unknown origin. It is recommended to perform this test in all patients with motor disorders, and especially with motor NP, with Guillain-Barré syndrome (GBS), with diseases of the proximal lower motor neurons.

Antibodies to ganglioside GD1b (anti-GD1b autoantibodies)

The analysis of anti-GD1b autoantibodies may be useful for the clinical evaluation of patients with Guillain-Barré syndrome (GBS) without ophthalmoplegia (see also anti-Q1b), with sensory NP, in particular with chronic sensory NP of large fibers (large nerve trunks) with ataxia. Anti-GM1 antibodies are found in approximately 5% of healthy individuals, especially the elderly. Determination of anti-GD1b autoantibodies can be useful: to screen for patients with evidence of inflammatory DNP but negative for anti-GM1 autoantibodies; to monitor the effectiveness of therapy for acute and chronic inflammatory DNP; as an adjunct in the diagnosis of NP of unknown origin. It is recommended that this analysis be performed in all patients with motor impairments, and especially those with motor NP.

Antibodies to ganglioside GQ1b (anti-GQ1b autoantibodies)

Miller-Fischer syndrome (MFS) is highly associated with the presence of polyclonal serum IgG antibodies to the GQ1b antigen, which can be found in the serum of more than 90% of patients with acute MFS. During the acute stage of the disease, antibody titers reach very high levels and disappear completely upon recovery. In healthy blood donors, patients with Guillain-Barré syndrome (GBS) without ophthalmoplegia, and in patients with other immunological or neurological diseases, anti-GQIb autoantibodies are not detected. MFS is a variant of GBS with which they have overlapping clinical and neurophysiological features. The similarity between MFS and GBS has recently been confirmed by the presence of anti-GQ1b in GBS patients with ophthalmoplegia. In some cases, IgA and IgM autoantibodies can also be detected in MFS, but to a lesser extent and only for a short period of time. The majority of patients suffering from MFS or GBS with ophthalmoplegia and having anti-GQ1b autoantibodies had a history of Campylobacter jejuni infection. This fact supports the hypothesis of molecular similarity between C. jejuni and GQ1B surface epitopes, and that MFS is initiated by prior C. jejuni infection.

Anti-interferon β antibodies (anti-IFNβ antibodies)

In recent years, recombinant interferon beta (rIFNβ) therapy has been used to treat relapsing-remitting multiple sclerosis (RRMS). Continuous prolonged (from a month to several years) administration of any exogenous substance can provoke an immune response. Many patients with RRMS treated with IFNβ develop anti-IFNβ antibodies that reduce the therapeutic effect of the drug. It has been shown that in patients with multiple sclerosis, only a small part of antiIFNβ antibodies is able to neutralize the immunomodulatory effect of IFNβ. Also shown is the determination of these antibodies in sensory NP, in Guillain-Barré syndrome (GBS).

Antibodies to sphingomyelin (SM)

CM (sphingomyelin) is a phospholipid, which includes sphingosine, fatty acid, phosphoric acid and choline. SM is a natural component of membranes and lipoprotein particles. SM is present in large amounts in the brain and nervous tissue. Suppression of SM biosynthesis in laboratory mice reduces plasma concentrations of cholesterol (CH) by 46%, and triglycerides by 44%, compared with the control group. In addition, the cholesterol content in LDL particles and very low density lipoproteins (VLDL) decreases and the concentration of high density lipoprotein cholesterol (HDL) increases. Studies on laboratory animals have shown that the suppression of SM synthesis also leads to a significant reduction in the severity of atherosclerotic lesions and macrophage infiltration. It is likely that the suppression of sphingolipid synthesis is a promising direction in the treatment of dyslipidemia and atherosclerosis. Antibodies to sphingolipids are involved in the pathogenesis of autoimmune demyelination and are found in multiple sclerosis and autoimmune encephalomyelitis.

Anti-laminin β antibodies

Laminin is the main glycoprotein of basement membranes, the extracellular matrix surrounding epithelial tissues, nerves, fat cells, smooth, striated and cardiac muscles. This multifunctional, high molecular weight, multidomain glycoprotein consists of 3 polypeptides - A, B1 and B2 linked together by interchain disulfide bridges. Laminin promotes cell adhesion, growth, migration and proliferation, neurite outgrowth, tumor metastasis, and possibly cellular differentiation. It is known that recombinant human antibodies to laminin block the development of vascular endothelium.

Anticochlear antibodies (anti-68 kD, hsp-70)

Hearing loss can be caused by many reasons. Some types of hearing loss may be reversible with early diagnosis and appropriate treatment. Sensorineural hearing loss (SNHL), commonly referred to as deafness associated with nerve damage, may be due to genetic or acquired factors such as infections, or may be due to immunological causes. In most cases, the cause of SNHL cannot be determined. Such cases are referred to as idiopathic SNHL. There is a subgroup of patients with idiopathic SNHL who respond very well to immunosuppressive therapy. Laboratory testing to identify these patients should include serum antibodies to the 68 kDa (hsp-70) inner ear antigen. 22% of patients with bilateral rapidly progressive SNHL and 30% of patients with Ménière's disease have antibodies to this antigen. Anti-68 kDa (hsp-70) antibodies also occur in approximately 60% of patients with bilateral and 35% of patients with unilateral Ménière's syndrome. In the group of patients who have unexplained progressive deafness, there is an approximately 30% chance that the hearing loss is of an immune etiology. Recent studies in a large cohort of 279 patients with idiopathic bilateral SNHL identified 90 (32%) positive cases of anti-68 kDa (hsp-70) antibodies (among them 63% women).

Antibodies to the 68 kDa antigen have been identified in patients whose hearing has improved with immunosuppressive therapy. It has been shown that 89% of patients with progressive bilateral SNHL in the active phase have antibodies to the 68 kDa antigen, while in patients with inactive disease, the results were always negative. Among patients who tested positive, 75% responded to steroid therapy, compared with 18% of patients who tested negative for antibodies to the 68 kDa antigen.

Frequency of anti-68 kDa (hsp-70) antibodies in idiopathic bilateral SNHL (IPBSNHL)

Disease	Patients	% positive
IPBSNHL	72	58
Otosclerosis	11	0
Kogan's syndrome	8	0
Healthy people	53	2

Moscicki RA et al. JAMA 272: 611-616, 1994

Correlation of anti-68kD (hsp-70) antibodies with disease activity

In retrospective studies, hsp-70 antibody testing has been shown to be the best predictor of response to corticosteroid therapy.

Anti-neuronal autoantibodies

Autoimmune diseases of the CNS are considered as paraneoplastic neurological diseases resulting from an antitumor response of the immune system. These diseases include paraneoplastic encephalomyelitis (PE), sensory neuropathy (PSN), progressive cerebellar degeneration (PCD), paraneoplastic myoclonus and ataxia (POMA), and Stiffmann's syndrome.

Clinical manifestations include memory loss, sensory loss, brain stem dysfunction, cerebellar, motor or autonomic dysfunction (PE or PSN); involuntary convulsive eye movements, myoclonus and ataxia (POMA). Reliable diagnosis of such conditions is a rather difficult task. In most cases, unfortunately, the tumor that causes the development of paraneoplastic syndrome is not detected by the time the patient has neurological symptoms. Paraneoplastic disorders are characterized by the presence of neuronal autoantibodies in the serum of patients. The detection of such antibodies is beneficial to the clinician because confirms the presence of an underlying tumor. Paraneoplastic neurological diseases can develop in small cell lung cancer, neuroblastoma, breast cancer, ovarian cancer, and testicular cancer. In paraneoplastic syndrome, the following autoantibodies are detected:

1. anti-Hu - antibodies to type I neuron nucleus (anti-neuronal nuclear antibody, ANNA-1), associated with small cell lung cancer, lead to the development of PE.

2. anti-Yo - antibodies to Purkinje cells (PCA-1), associated with ovarian cancer or breast cancer, lead to the development of PCD.

3. anti-Ri - antibodies to type II neuron nucleus (ANNA-2), associated with neuroblastoma (children) and fallopian tube or breast cancer (adults), leads to the development of POMA.

The presence of such antibodies confirms the clinical diagnosis of paraneoplastic syndrome and leads to a targeted search for the underlying tumor.

These markers help to differentiate between true paraneoplastic syndrome and other inflammatory diseases of the nervous system similar to paraneoplastic syndrome.

Western blotting is a sensitive method that allows simultaneous screening and confirmatory testing to detect autoantibodies to various neuronal antigens present in the nuclei or in the cytoplasm of cells. Anti-Hu and anti-Ri reactions can be easily observed in the 35-40 kDa and 55 kDa regions, respectively.

Antibodies to ribosomal P proteins and RNA

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of various circulating autoantibodies. Patients suffering from SLE often experience mental disorders, their range is very wide. CNS-related disease manifestations occur in a large number of SLE patients and cause behavioral changes reminiscent of schizophrenia. Approximately 90% of psychiatric SLE patients have circulating autoantibodies to ribosomal P proteins. This is a group of autoantibodies directed to the ribosomal phosphoproteins P0 (38 kDa), P1 (19 kDa), and P2 (17 kDa). An increase in autoantibodies to ribosomal P proteins may precede the onset of a psychotic episode. In addition, in such patients, with a frequency of 17 to 80% (according to various literature data), autoantibodies to RNA directed against 28S rRNA are also detected. Anti-ribosomal P autoantibodies usually coexist with anti-RNA autoantibodies. A correlation has been shown between anti-RNA antibodies and disease activity. Thus, both anti-ribosomal P and anti-RNA autoantibodies contribute to the pathogenesis of CNS disorders in SLE. 1

The concentration of myelin basic protein (MBP) and neuron-specific enolase (NSE) in blood serum was studied in 84 patients with chronic hepatitis (CH) (viral etiology HBV, HCV - 38; alcoholic etiology - 17; autoimmune hepatitis - 11; hepatitis of mixed etiology - 18 ) and 77 liver cirrhosis (LC) (viral etiology HBV, HCV, HBV + HCV - 27; primary biliary cirrhosis - 10, alcoholic etiology - 18; mixed etiology - 22). Control group - 30 practically healthy persons (donors). Serum MBP and NSE concentrations were determined by enzyme-linked immunosorbent assay using commercial test kits 449-5830 DSL MBP and 420-10 Fujirebio NSE. According to the results of the study, in alcoholic liver lesions, both at the stage of chronic hepatitis and the formed cirrhosis, a significant increase in the concentration of blood MBP was observed compared with viral lesions. The concentration of NSE in patients with cirrhosis of the studied etiological groups, in contrast to CG, did not differ significantly.

myelin basic protein

neuron-specific enolase

chronic hepatitis

cirrhosis of the liver

hepatic encephalopathy.

1. Zhukova I.A. Neuron-specific enolase as a non-specific marker of the neurodegenerative process / I.A. Zhukov, V.M. Alifirova, N.G. Zhukov // Bulletin of Siberian Medicine. - 2011. - T. 10. - No. 2. - S. 15-21.

2. Belopasov V.V. Clinical differentiation of hepatic encephalopathy in patients with liver cirrhosis / V.V. Belopasov, R.I. Mukhamedzyanova, M.K. Andreev, B.N. Levitan // Vyatka Medical Bulletin. - 2002. - No. 1. - S. 46-47.

3. Ivashkin V.T. Liver diseases and hepatic encephalopathy / V.T. Ivashkin, F.I. Komarov, I.O. Ivanikov // Russian Medical Journal. - 2001. - T. 3. - No. 12. - S. 150-155.

4. Levitan B.N. Chronic liver pathology and intestinal microbiocenosis (clinical and pathogenetic aspects) / B.N. Levitan, A.R. Umerova, N.N. Larina. - Astrakhan: AGMA, 2010. - 135 p.

5. Levitan B.N. Changes in the concentration of myelin basic protein in blood serum in liver diseases / B.N. Levitan, A.V. Astakhin, O.O. Evlasheva // Experimental and clinical gastroenterology. - 2015. - No. 2. - P. 93.

6. Pavlov Ch.S. Hepatic encephalopathy: pathogenesis, clinic, diagnosis, therapy / Ch.S. Pavlov, I.V. Damulin, V.T. Ivashkin // Russian Journal of Gastroenterology, Hepatology, Coloproctology. - 2016. - No. 1. - P. 44-53.

7. Toropova N.E. Evaluation of the information content of neuron-specific enolase determined by enzyme immunoassay / N.E. Toropova, E.A. Dorofeeva, S.P. Dvoryaninova, Zh.P. Vasieva // Clinical laboratory diagnostics. - 1995. - No. 1. - S. 15–17.

8. Chekhonin V.P. Myelin basic protein. Structure, properties, functions, role in the diagnosis of demyelinating diseases / V.P. Chekhonin, O.I. Gurina, T.B. Dmitrieva et al. // Biomedical chemistry. - 2000. - T. 46. - No. 6. - S. 549–563.

9. Arguedas M.R. Influence of hepatic encephalopathy on healthy – related quality of life in patients with cirrhosis / M.G. Arguedas, T.G. Delawrence, B.M. Mcguire // Digestive diseases and sciences. - 2003. - V. 48. - P. 1622-1626.

10. Butterworth R.F. Pathophysiology of hepatic encephalopathy: The concept of synergism // Hepatol. Res. - 2008. - V. 38. - P. 116-121.

11. Isgro M. Neuron – specific enolase as a biomarker: biochemical and clinical aspects / M. Isgro, P. Bottoni, R. Scatena // AdvExp Mad Biol. - 2015. - Vol. 867. - P. 125-143.

12. Persson L. 100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system / L. Persson, H.G. Hardemark, J. Gustaffson et al. // Stroke. - 1987. - Vol. 18. - P. 911-918.

13. Rabinowicz A. NSE as a useful prognostic factor for patients after cerebral hypoxia / A. Rabinowicz, H. Reiber // Epilepsia. - 1996. - Vol. 37. - P. 122-125.

14. Tzakos A. Structure and function of the myelin proteins: current status and perspectives in relation to multiple sclerosis / A. Tzakos, A. Troganis, V. Theodorou // Curr. Med. Chem. - 2005. - Vol. 12. - P. 1569-1587.

Chronic hepatitis (CH) and liver cirrhosis (LC) are polyetiological diseases. It is well known that infection with hepatotropic viruses is the main etiological factor leading to the development of CG, and alcohol abuse, in turn, is the second main cause of this pathology.

The course and prognosis of liver diseases is largely determined by the presence and severity of damage to the central nervous system (CNS). Hepatic encephalopathy (PE) is a complex of potentially reversible neuropsychiatric disorders caused by damage to the central nervous system by toxic substances that are not neutralized by a pathologically altered liver, arising primarily as a result of acute or chronic liver failure. Given the extreme aggressiveness of these substances, it can be assumed that under their influence, the destruction of the nervous tissue occurs with the release of its decay products into the liquid media of the body.

A fairly large number of studies have been devoted to the study of the diagnostic and prognostic significance of such markers of neurodestruction as myelin basic protein (MBP) and neuron-specific enolase (NSE) in various pathological conditions of the CNS. At the same time, the issue of their diagnostic value in chronic diffuse liver diseases (CDLD) of various etiologies remains poorly understood. In this regard, the study of MBP and NSE, depending on the etiology of CDPD, is relevant and promising.

Purpose: to study the diagnostic significance of determining the concentration of myelin basic protein and neuron-specific enolase in blood serum, depending on the etiology of CDPD.

Materials and methods. To solve the tasks for the period from 2012 to 2014, 84 patients with chronic hepatitis (viral etiology HBV, HCV - 38; alcoholic etiology - 17; autoimmune hepatitis - 11; mixed etiology - 18) and 77 LC (viral etiology HBV, HCV) were examined. , HBV + HCV - 27; primary biliary cirrhosis - 10, alcoholic etiology - 18; mixed etiology - 22), who were hospitalized in the gastroenterological department of the GBUZ JSC "AMOKB". Among the examined patients with liver pathology, a group of 17 patients was identified, which was not included in the list of patients with chronic hepatitis. This group consisted of patients with acute alcoholic hepatitis (AAH), occurring with symptoms of severe hepatocellular insufficiency. The control group consisted of 30 practically healthy individuals (donors).

The studies were carried out on the basis of our own observations and data from medical records (clinical history of the disease, outpatient card, conclusions of specialists in paraclinical methods of examination).

Patients were admitted to the clinic in the stage of exacerbation of the underlying disease. The currently accepted classifications were used in making the diagnosis. Clinical diagnosis was established on the basis of patients' complaints, anamnesis, physical data, laboratory and instrumental research methods. In the anamnesis, special attention was paid to surgical interventions, blood transfusions, alcohol and intravenous drug use, long-term use of hepatotoxic drugs, and the presence of hereditary diseases.

Exclusion criteria: concomitant pathology of the central nervous system, treatment with drugs that have a neurotoxic side effect.

Serum MBP and NSE concentrations were determined by enzyme-linked immunosorbent assay using reagent kits of commercial test systems 449-5830 DSL MBP and 420-10 Fujirebio NSE.

Statistical data processing was performed using the Statistica 6.0 software package. Student's parametric test (t) was used to quantify the characteristics of two unrelated groups. Correlation analysis with the calculation of the correlation coefficient (r) was performed using the Spearman test. Differences were considered statistically significant at the achieved significance level p<0,05.

Results and discussion. The concentration of MBP in patients with CG of viral etiology averaged 1.9±0.27 ng/ml, mixed - 2.3±0.3 ng/ml, autoimmune 2.17±0.19 ng/ml, which did not differ significantly from the results obtained in the donor group — 1.9±0.3 ng/ml (p>0.05) (Fig. 1). A more significant increase in the level of MBP was found in patients with chronic hepatitis of alcoholic etiology, amounting to 2.9±0.39 ng/ml, which significantly exceeded the values ​​obtained in the control group, as well as in patients with viral etiology of the disease (p<0,05). Максимальная концентрация ОБМ в сыворотке крови была выявлена в группе больных ОАГ, составив в среднем 5,4±0,17 нг/мл, что достоверно превышало показатели, характерные как для здоровых лиц, так и для больных хроническим гепатитом вирусной, смешанной, аутоиммунной и алкогольной этиологии (р<0,05). В исследуемой группе пациентов ОАГ максимальная концентрация ОБМ в периферической крови наблюдалась в 75% случаев.

The results obtained in the study of the concentration of NSE in patients with CG and OAH were somewhat different (Fig. 2).

The concentration of NSE in patients with chronic hepatitis of viral etiology was 6.9±0.41 ng/ml, mixed - 7.4±0.37 ng/ml, autoimmune - 6.4±0.52 ng/ml. The results obtained are close and did not significantly differ from the values ​​obtained in the control group - 6.49±0.41 ng/ml (p>0.05).

The level of NSE in patients with chronic hepatitis of alcoholic etiology averaged 8.1±0.51 ng/ml, which is significantly higher than in the control group, as well as in patients with autoimmune and chronic hepatitis of viral etiology (p<0,05).

The most significant increase in the concentration of NSE, as well as MBP, was found in patients with OAH, averaging 14.3 ± 0.47 ng / ml, and in 81% of the examined patients, the results obtained significantly exceeded those characteristic for donors, as well as patients with chronic hepatitis of viral, mixed, autoimmune and alcoholic etiology (r<0,05), достигая 25 нг/мл.

Rice. 1. The concentration of MBP in patients with chronic hepatitis, depending on the etiology:

Rice. 2. The concentration of NSE in patients with chronic hepatitis, depending on the etiology:

1 - viral hepatitis (HBV, HCV); 2 - autoimmune hepatitis; 3 - alcoholic hepatitis;

4 - hepatitis of mixed etiology; 5 - control

A high concentration in the peripheral blood of the studied markers of nervous tissue damage, such as MBP and NSE, which we detected in alcoholic liver damage, is probably a manifestation of demyelinating processes that are often observed in this pathology. The revealed patterns speak in favor of the fact that the reasons for the development of atrophic changes in the brain and damage to nerve fibers (markers of which are MBP and NSE), which are often found in people who abuse alcohol, are not only the neurotoxic effect of ethanol and its metabolites, but also factors such as as liver dysfunction, malnutrition, as well as a deficiency of B vitamins and nicotinic acid.

As mentioned above, the main etiological factor leading to the occurrence of chronic hepatitis is a hepatotropic viral infection.

The concentrations of MBP and NSE in the blood serum of patients with chronic hepatitis depending on the type of hepatotropic virus (B and C) were close and did not differ significantly from each other, as well as from the indicators obtained in the control (p>0.05). Also, there were no significant differences in the concentrations of the studied markers of destruction of the nervous tissue in CHC patients with genotype 1 and genotype "non-1" (2 and 3a). Consequently, the level in the peripheral blood of the parameters we studied does not depend on the type of viruses.

It is noteworthy that the concentrations of MBP and NSE in patients with CG of viral and CG of mixed etiology (viral + alcoholic) do not differ significantly from each other, as well as from the results obtained in the control (p>0.05). At the same time, it was found that the combination of viral and alcoholic factors has a more significant effect on the state of the studied markers of neurodestruction than only with viral etiology. So, if in patients with mixed etiology, the level of MBP in 42% of cases exceeded the indicators characteristic of healthy individuals, then in chronic viral hepatitis only in 30%. The concentration of NSE, respectively, in 39% of cases exceeded the indicators characteristic of healthy individuals with a mixed etiology of the disease, and only in 31% with a viral one. In our opinion, this indirectly indicates that a high concentration of the studied markers of nerve tissue damage, detected in some patients with CG, is more characteristic in the presence of such an etiological factor as alcohol abuse.

Conducted in the general group of patients with CG correlation analysis of the values ​​of MBP and NSE showed the absence of significant relationships between these indicators. At the same time, in the group of patients with alcoholic liver damage, a positive weak correlation was found between the concentrations of MBP and NSE (r = 0.45), which, in our opinion, indirectly indicates similar mechanisms leading to an increase in the level of these damage markers. nervous tissue in this pathology.

The revealed patterns make it possible to use the determination of the level of MBP and NSE in the blood serum of patients with chronic hepatitis as an additional marker in the diagnosis of various etiological forms of chronic hepatitis, primarily alcoholic etiology, as well as to identify the presence of demyelinating processes in this pathology.

Given that there are etiological features of the nature of the course of cirrhosis, the rate of progression, the development of complications, a study was made of the concentration of MBP and NSE depending on the etiology of the disease. 27 patients (35%) were diagnosed with cirrhosis of viral etiology, 18 (23%) - alcoholic, 22 (29%) had a history of alcohol abuse and viral hepatitis at the same time (mixed etiology), 10 patients (13%) had diagnosed with primary biliary cirrhosis. The concentrations of MBP and NSE in patients with cirrhosis of viral etiology were 2.3±0.42 and 8.2±0.56 ng/ml, mixed - 2.7±0.34 and 7.8±0.43 ng/ml, biliary 3.2±0.39 and 8.3±0.39 ng/ml, alcoholic 3.4±0.3 and 8.9±044 ng/ml, respectively.

Mean values ​​of NSE concentration in groups of patients with cirrhosis of viral, biliary and alcoholic etiology are significant (p<0,05) превышали показатели в контрольной группе. В то же время отсутствовали достоверные различия концентраций НСЕ в периферической крови в зависимости от этиологии ЦП. Результаты проведённого исследования свидетельствуют, что на стадии ЦП, в отличие от ХГ, концентрация данного маркера нейродеструкции в периферической крови не связана с этиологией заболевания.

Consequently, at the stage of the formed cirrhosis, the causes that cause an increase in the level of NSE in the peripheral blood are somewhat different from those in hepatitis (OAG, CG). Probably, the leading role is played by the neurotoxic effect of endogenous intoxication products circulating in the blood in severe liver dysfunction, and not the direct effect of ethanol and its metabolites.

In addition to the fact that NSE primarily refers to intracellular enzymes of the central nervous system and is considered one of the most specific indicators of its damage, at the same time, there are five molecular forms of NSE isoenzymes found not only in neurons, but also in neuroendocrine cells, skeletal muscles, liver , erythrocytes and platelets, and fluctuations in its general level can be directly related to severe liver dysfunction and the development of various complications characteristic of cirrhosis.

The results obtained in the study of the level of MBP in the peripheral blood of patients with cirrhosis of various etiologies differed somewhat.

Thus, the results of the study indicate that in cirrhosis of biliary (3.2±0.39 ng/ml) and alcoholic (3.4±0.3 ng/ml) etiology, the values ​​of MBP are significantly increased compared to the control group - 1.9 ±0.3 ng/ml and patients with liver cirrhosis of viral etiology - 2.3±0.42 ng/ml (p<0,05). При ЦП вирусной этиологии уровень ОБМ был наиболее низким, сопоставимым с показателями, полученными в контроле (р>0.05). With cirrhosis of mixed etiology (2.7±0.34 ng/ml), its level was slightly higher than with viral cirrhosis, and, accordingly, more than in the control, but no significant differences were found when comparing the results obtained (p>0.05) . Despite a significant difference in blood volume parameters in patients with cirrhosis of alcoholic etiology and PBC compared with the control, we did not reveal a significant difference in the level of the studied protein between these studied groups of patients (p>0.05). The average values ​​of the concentration of MBP in peripheral blood in patients with liver cirrhosis of mixed and alcoholic etiology differed slightly from each other: 2.7±0.34 and 3.4±0.3 ng/ml, respectively, no significant difference was found (p>0 .05). The results obtained are presented in fig. 3 and 4.

Rice. 3. The concentration of NSE in patients with cirrhosis depending on the etiology: 1 - cirrhosis of viral etiology (HBV, HCV); 2 - primary biliary cirrhosis; 3 - cirrhosis of alcoholic etiology; 4 - CP of mixed etiology; 5 - control

Rice. 4. The concentration of MBP in patients with cirrhosis depending on the etiology: 1 - cirrhosis of viral etiology (HBV, HCV); 2 - primary biliary cirrhosis; 3 - cirrhosis of alcoholic etiology; 4 - CP of mixed etiology; 5 - control

Thus, the revealed patterns are similar to the results obtained in patients with CG, in the group of which the maximum concentration of plasma MBP was also observed in the alcoholic etiology of the disease.

Conclusion. In alcoholic liver lesions, both at the stage of chronic hepatitis and formed cirrhosis, there is a significant increase in the concentration of blood MBP compared with viral lesions, which confirms our assumption that, in addition to the neurotoxic effect of endogenous intoxication products circulating in the blood in severe liver lesions , a significant role in the processes of neurodestruction and demyelination of nerve fibers is played by the direct damaging effect of ethanol and its metabolites.

Bibliographic link

Astakhin A.V., Evlasheva O.O., Levitan B.N. MYELIN BASIC PROTEIN AND NEURON-SPECIFIC SERUM ENOLASE IN LIVER DISEASES OF VARIOUS ETIOLOGIES // Modern problems of science and education. - 2017. - No. 2.;
URL: http://site/ru/article/view?id=26162 (date of access: 12/17/2019).

We bring to your attention the journals published by the publishing house "Academy of Natural History"

The myelin sheath of nerves is 70-75% lipids and 25-30% proteins. The composition of its cells also includes lecithin, a representative of phospholipids, whose role is very large: it takes part in many biochemical processes, improves the body's resistance to toxins, and lowers cholesterol levels.

The use of products containing lecithin is a good prevention and one of the ways to treat diseases associated with impaired activity of the nervous system. This substance is part of many cereals, soy, fish, egg yolk, brewer's yeast. Lecithin also contains: liver, olives, chocolate, raisins, seeds, nuts, caviar, dairy and sour-milk products. An additional source of this substance can be biologically active food additives.

You can restore the myelin sheath of nerves by including foods containing the amino acid choline in your diet: eggs, legumes, beef, nuts. Omega-3 polyunsaturated fatty acids are very useful. They are found in fatty fish, seafood, seeds, nuts, linseed oil and flaxseed. The source of omega-3 fatty acids can serve: fish oil, avocados, walnuts, beans.

The composition of the myelin sheath includes vitamins B1 and B12, so it will be useful for the nervous system to include rye bread, whole grains, dairy products, pork, fresh herbs in the diet. It is very important to consume enough folic acid. Its sources: legumes (peas, beans, lentils), citrus fruits, nuts and seeds, asparagus, celery, broccoli, beets, carrots, pumpkin.

Restoration of the myelin sheath of nerves contributes to copper. It contains: sesame seeds, pumpkin seeds, almonds, dark chocolate, cocoa, pork liver, seafood. For the health of the nervous system, it is necessary to include foods containing inositol in the diet: vegetables, nuts, bananas.

It is very important to support the immune system. In the presence of sources of chronic inflammation or autoimmune diseases in the body, the integrity of the nerves is disturbed. In these cases, in addition to the main therapy, food and herbal anti-inflammatory drugs should be introduced into the menu: green tea, rosehip, nettle, yarrow infusions, as well as foods rich in vitamins C and D. Vitamin C is found in large quantities in citrus fruits, berries, kiwi, cabbage, sweet peppers, tomatoes, spinach. Sources of vitamin D are eggs, dairy products, butter, seafood, fatty fish, cod liver and other fish.

A diet to restore the myelin sheath of nerves should contain sufficient amounts of calcium. It is part of many products: milk, cheese, nuts, fish, vegetables, fruits, cereals. For the full absorption of calcium, it is necessary to include magnesium (found in nuts, wholemeal bread) and phosphorus (found in fish) in the diet.

6. MYELIN PROTEINS

The protein composition of myelin is peculiar, but much simpler than in neurons and glial cells.

Myelin contains a large proportion of cationic protein - CBM. It is a relatively small polypeptide with Mg = 16–18 kD. CBM contains a significant proportion of diamino acids, and at the same time, about half of its constituent amino acids are non-polar. This provides, on the one hand, close contact with the hydrophobic components of myelin lipids, and, on the other hand, determines its ability to form ionic bonds with acidic lipid groups.

The so-called Folch proteolipid proteins, which make up most of the rest of the myelin proteins, are characterized by an unusually high hydrophobicity. In turn, the main of these proteins is lipophilin, in which 2/3 of the constituent amino acids are non-polar. Of interest is a certain selectivity of contacts between lipophilin and lipids, for example, the displacement of cholesterol from its environment. It is believed that this is due to the peculiarities of the secondary structure of lipophilin.

The proportion of the so-called Wolfgram protein is also quite large - an acidic proteolipid, quite rich in dicarboxylic amino acid residues, and, at the same time, containing about half of non-polar amino acid residues.

Finally, from several dozen other myelin proteins, we note a myelin-associated glycoprotein located on the extracellular surface of membranes; it is also found in pre-myelination oligodendrocytes and in the myelin of the peripheral nervous system. In the human CNS, it is represented by three polypeptide chains with M g = 92, 107, 113 kD, and in the peripheral nervous system, by one protein with M g = 107 kD. MAG belongs to glycoproteins with a relatively low content of carbohydrate residues - about 30% of the mass of the molecule, but contains a set of carbohydrates characteristic of glycoproteins: N-acetylglucosamine, N-acetylneuraminic acid, fucose, mannose and galactose. The protein part of the molecule is characterized by a high content of glutamic and aslaric acids.

The functions of the Wolfgram protein and MAG are unknown, except for general considerations about their participation in the organization of the structure of the myelin sheaths.

7. NEUROSPECIFIC GLIA PROTEINS

The S-100 protein is found in both neurons and glial cells, and its share in the latter is high - about 85%.

In 1967, a neurospecific a 2 -glycoprotein with a molecular weight of 45 kD was isolated from the a 2 -globulins of the brain. In the human brain, it appears at the 16th week of embryonic development. Its carbohydrate components include glucosamine, mannose, glucose, galactose, galactosamine, and N-acetylneuraminic acid. and 2-glycoprotein is localized only in astrocytes, but is absent in neurons, oligodendrocytes and endothelial cells. Therefore, it can be considered as one of the specific markers of astrocytes.

Another protein is again characteristic only of glial cells. It was isolated from areas of the human brain rich in fibrous astrocytes, and subsequently - in much larger quantities - from the brain of patients with multiple sclerosis. This substance was named glial fibrillar acidic protein. It is specific only to the CNS, and it is not found in the PNS. Its content in the white matter of the brain exceeds that in the gray matter. In the ontogeny of mice, the maximum content of GFA is observed between the 10th and 14th days of postnatal development; coincides in time with the period of myelination and the peak of differentiation of astrocytes. The molecular weight of the protein is 40–54 kD. The glial localization of this protein also allows it to be used as a "marker" protein for these cells.

The functions of a 2 -glycoprotein and GFA protein are unknown.

As for microglial proteins, one should keep in mind the participation of these cells in the construction of myelin. Many of the myelin proteins are found in microglia.

Glia also contains many receptor and enzymatic proteins involved in the synthesis of second messengers, precursors of neurotransmitters, and other regulatory compounds that can be classified as neurospecific.

8. INTENSITY OF PROTEIN METABOLISM IN DIFFERENT SECTIONS OF THE NERVOUS SYSTEM

The modern concept of the dynamic state of proteins in the nervous tissue was established thanks to the use of isotopes by A.V. Palladin, D. Richter, A. Laita and other researchers. Starting from the late 1950s and during the 1960s, various precursors of their biosynthesis labeled with C, H, S were used in the study of protein metabolism. It was shown that proteins and amino acids in the brain of an adult animal metabolize, in general, more intensely than in other organs and tissues.

For example, in experiments in vivo using uniformly labeled C-1-6-glucose as a precursor, it turned out that, according to the intensity of amino acid formation due to glucose, a number of organs can be arranged in the following order:

brain > blood > liver > spleen and lungs > muscle.

A similar picture was observed when using other labeled precursors. It has been shown that the carbon skeleton of amino acids, especially monoaminodicarboxylic acids and, above all, glutamate, is intensively synthesized from C-acetate in the brain; from monoaminomonocarboxylic acids, glycine, alanine, serine, etc. are quite intensively formed. It should be noted that glutamate occupies a special place in the metabolism of amino acids. In vitro experiments using labeled glutamate showed that if only one glutamic acid is added to the reaction medium of the brain homogenate, then it can be a source of formation of 90–95% of amino acids.

Numerous studies have been carried out to study the differences in the intensity of metabolism of total and individual proteins using labeled precursors. In vivo experiments using C-glutamate showed that it is incorporated 4–7 times more intensively into gray matter proteins than white matter. In all cases, the intensity of the exchange of total proteins of the gray matter of the cerebral hemispheres and cerebellum was significantly higher than that of the white matter of the same parts of the brain, no matter what precursor was used in the study. At the same time, the difference in the intensity of metabolism of total gray matter proteins compared with white matter proteins takes place not only in the norm, but, as a rule, also in various functional states of the body.

Studies were also carried out to study differences in the intensity of incorporation of labeled precursors into total proteins of the central and peripheral nervous systems. It turned out that despite significant differences in the composition, metabolism, and functional activity of various parts of the CNS and PNS, as well as the complexity and heterogeneity of the proteins that make up them, the total CNS proteins of adult animals are updated much more intensively than the total PNS proteins.

A lot of research is devoted to the metabolism of proteins in various parts of the brain. For example, when studying the distribution of radioactivity in the brain after the administration of C-glutamate, it turned out that the gray matter of the cerebral hemispheres accounts for 67.5 radioactivity, the cerebellum - 16.4, the medulla oblongata - 4.4, and the share of other parts of the brain - about 11.7. In experiments in vivo, when various precursors, namely C-glutamate, C-1-6-glucose, C-2-acetate, were administered to adult animals, it turned out that, according to the intensity of label incorporation into total proteins, different parts of the nervous system are arranged in the following sequence: gray matter of the cerebral hemispheres and cerebellum > thalamus > optic tubercle > middle and diencephalon > pons Varolii > medulla oblongata > white matter of the cerebral hemispheres and cerebellum > spinal cord > sciatic nerve > myelin.

There were also studies devoted to the study of the intensity of protein metabolism in various parts of the CNS using the autoradiographic method. A similar picture was obtained: the most intense inclusion of the label took place in the proteins of the gray matter of the cerebral hemispheres and cerebellum, the slowest in the spinal cord, and even more slowly in the proteins of the sciatic nerve. As for the subcortical formations, the intensity of their protein metabolism was average between the rate of renewal of the proteins of the gray and white matter of the cerebral hemispheres and the cerebellum. Less significant differences are observed between individual subcortical formations than between the metabolic activity of white and gray matter.

The total proteins of different areas of the cerebral cortex, frontal, temporal, parietal, and occipital, were also studied. According to Welsh and VAPalladin, the proteins of the sensory area of ​​the cortex have a higher renewal rate, and the proteins of the temporal lobe of the cerebral cortex have a lower one. The same authors showed that higher protein renewal is characteristic of phylogenetically younger and functionally more active structural formations of the brain.

Against the backdrop of the generally highly renewable brain proteins, a few rather inert proteins deserve special mention. These include the histones of the neurons of the neocortex, the cationic proteins of the chromatin of these cells. In an adult organism, neocortical neurons do not multiply. Accordingly, the rate of histone renewal is very low. The average time for the renewal of half of the molecules of some histone fractions is measured in tens of days.

There are no absolutely inert proteins in the brain, and individual proteins and protein complexes of neurons undergo continuous restructuring associated with their participation in the functional activity of neurons and neuroglia. In addition to the synthesis and breakdown of whole protein molecules, changes occur in their structure, which occur, in particular, during amination and deamination of brain proteins. They should be considered as a partial renewal of individual fragments of the protein molecule.

1. In the nervous tissue, neurospecific proteins characteristic only of it were found. Chemically, they can be acidic or basic, simple or complex, and are often glycoproteins or phosphoproteins. Many neurospecific proteins have a subunit structure. The number of discovered neurospecific proteins has already exceeded 200 and is growing rapidly.

2. Neurospecific proteins are directly or indirectly involved in the implementation of all functions of the nervous system - the generation and conduction of a nerve impulse, the processes of processing and storing information, synaptic transmission, cell recognition, reception, etc.

3. According to localization in the tissue of the nervous system, exclusively or predominantly neuronal and glial neurospecific proteins are distinguished. According to subcellular localization, they can be cytopyasmatic, nuclear or membrane-bound. Of particular importance are neurospecific proteins localized in the membranes of synaptic formations.

4. Many acidic potassium-binding neurospecific proteins are involved in ion transport processes. It is assumed that, in particular, they play a significant role in the formation of memory.

5. A special group of neurospecific proteins are contractile proteins of the nervous tissue, which provide orientation and mobility of cytostructural formations, active transport of a number of neuron components and participate in neurotransmitter processes in synapses.

6. The group of neurospecific proteins associated with humoral regulation carried out by the brain includes some glycoproteins of the hypothalamus, as well as neurophysins and similar proteins that are carriers of peptide regulators.

7. A variety of neurospecific glycoproteins are involved in the formation of myelin, in the processes of cell adhesion, neuroreception and mutual recognition of neurons in ontogenesis and regeneration.

8. A number of neurospecific proteins are brain isoenzymes of known enzymes, such as enolase, aldolase, creatine kinase, etc.

9. Many neurospecific proteins are very actively metabolized in the brain of animals, and the intensity of metabolism is different in different parts of the brain and depends on the functional state of the nervous system. On the whole, brain proteins significantly exceed the proteins of other tissues and organs in terms of the intensity of renewal.

The nervous system performs the most important functions in the body. It is responsible for all actions and thoughts of a person, forms his personality. But all this complex work would not be possible without one component - myelin.

Myelin is a substance that forms the myelin (pulp) sheath, which is responsible for the electrical insulation of nerve fibers and the speed of transmission of electrical impulses.

Anatomy of myelin in the structure of the nerve

The main cell of the nervous system is the neuron. The body of a neuron is called the soma. Inside it is the core. The body of a neuron is surrounded by short processes called dendrites. They are responsible for communicating with other neurons. One long process departs from the soma - the axon. It carries an impulse from a neuron to other cells. Most often, at the end, it connects to the dendrites of other nerve cells.

The entire surface of the axon is covered by the myelin sheath, which is a process of the Schwann cell devoid of cytoplasm. In fact, these are several layers of the cell membrane wrapped around the axon.

The Schwann cells that envelop the axon are separated by nodes of Ranvier, which lack myelin.

Functions

The main functions of the myelin sheath are:

• axon isolation;
• acceleration of impulse conduction;
• energy savings due to the conservation of ion flows;
• support of the nerve fiber;
• axon nutrition.

How impulses work

Nerve cells are isolated due to their shell, but still interconnected. The sites where cells touch are called synapses. This is the place where the axon of one cell and the soma or dendrite of another meet.

An electrical impulse can be transmitted within a single cell or from neuron to neuron. This is a complex electrochemical process, which is based on the movement of ions through the shell of the nerve cell.

In a calm state, only potassium ions enter the neuron, while sodium ions remain outside. At the moment of excitement, they begin to change places. The axon is positively charged internally. Then sodium ceases to flow through the membrane, and the outflow of potassium does not stop.

The change in voltage due to the movement of potassium and sodium ions is called an "action potential". It spreads slowly, but the myelin sheath that envelops the axon accelerates this process by preventing the outflow and inflow of potassium and sodium ions from the axon body.

Passing through the interception of Ranvier, the impulse jumps from one section of the axon to another, which allows it to move faster.

After the action potential crosses the gap in myelin, the impulse stops and the resting state returns.

This mode of energy transfer is characteristic of the CNS. In the autonomic nervous system, axons are often found covered with little or no myelin. Jumps between Schwann cells are not carried out, and the impulse passes much more slowly.

Composition

The myelin layer consists of two layers of lipids and three layers of protein. There are much more lipids in it (70-75%):

• phospholipids (up to 50%);
• cholesterol (25%);
• glaktocerebroside (20%), etc.

The protein layers are thinner than the lipid ones. The protein content in myelin is 25-30%:

• proteolipid (35-50%);
• myelin basic protein (30%);
• Wolfgram proteins (20%).

There are simple and complex proteins of the nervous tissue.

The role of lipids in the structure of the shell

Lipids play a key role in the structure of the pulp membrane. They are the structural material of the nervous tissue and protect the axon from the loss of energy and ion currents. Lipid molecules have the ability to restore brain tissue after damage. Myelin lipids are responsible for the adaptation of the mature nervous system. They act as hormone receptors and communicate between cells.

The role of proteins

Of no small importance in the structure of the myelin layer are protein molecules. They, along with lipids, act as a building material of the nervous tissue. Their main task is to transport nutrients to the axon. They also decipher the signals entering the nerve cell and speed up the reactions in it. Participation in metabolism is an important function of myelin sheath protein molecules.

Myelination defects

Destruction of the myelin layer of the nervous system is a very serious pathology, due to which there is a violation of the transmission of the nerve impulse. It causes dangerous diseases, often incompatible with life. There are two types of factors that influence the occurrence of demyelination:

• genetic predisposition to the destruction of myelin;
• influence on myelin of internal or external factors.
• Demyelization is divided into three types:
• acute;
• remitting;
• acute monophasic.

Why destruction occurs

The most common causes of destruction of the pulpy membrane are:

• rheumatic diseases;
• a significant predominance of proteins and fats in the diet;
• genetic predisposition;
• bacterial infections;
• heavy metal poisoning;
• tumors and metastases;
• prolonged severe stress;
• bad ecology;
• pathology of the immune system;
• long-term use of neuroleptics.

Diseases due to demyelination

Demyelinating diseases of the central nervous system:

1. Canavan disease- a genetic disease that occurs at an early age. It is characterized by blindness, problems with swallowing and eating, impaired motor skills and development. Epilepsy, macrocephaly and muscular hypotension are also a consequence of this disease.
2. Binswanger's disease. Most often caused by arterial hypertension. Patients expect thinking disorders, dementia, as well as violations of walking and the functions of the pelvic organs.
3. . May cause damage to several parts of the CNS. He is accompanied by paresis, paralysis, convulsions and impaired motor skills. Also, as symptoms of multiple sclerosis are behavioral disorders, weakening of the facial muscles and vocal cords, impaired sensitivity. Vision is disturbed, the perception of color and brightness changes. Multiple sclerosis is also characterized by disorders of the pelvic organs and degeneration of the brainstem, cerebellum, and cranial nerves.
4. Devic's disease- demyelination in the optic nerve and spinal cord. The disease is characterized by impaired coordination, sensitivity and functions of the pelvic organs. It is distinguished by severe visual impairment and even blindness. In the clinical picture, paresis, muscle weakness and autonomic dysfunction are also observed.
5. Osmotic demyelination syndrome. It occurs due to a lack of sodium in the cells. Symptoms are convulsions, personality disorders, loss of consciousness up to coma and death. The consequence of the disease are cerebral edema, hypothalamic infarction and hernia of the brain stem.
6. Myelopathy- various dystrophic changes in the spinal cord. They are characterized by muscle disorders, sensory disturbances, and pelvic organ dysfunction.
7. Leukoencephalopathy- destruction of the myelin sheath in the subcortex of the brain. Patients suffer from constant headache and epileptic seizures. There are also visual, speech, coordination, and walking impairments. Sensitivity decreases, personality and consciousness disorders are observed, dementia progresses.
8. Leukodystrophy- a genetic metabolic disorder that causes the destruction of myelin. The course of the disease is accompanied by muscle and movement disorders, paralysis, impaired vision and hearing, and progressive dementia.

Demyelinating diseases of the peripheral nervous system:

1. Guillain-Barré syndrome is an acute inflammatory demyelination. It is characterized by muscle and motor disorders, respiratory failure, partial or complete absence of tendon reflexes. Patients suffer from heart disease, disruption of the digestive system and pelvic organs. Paresis and sensory disturbances are also signs of this syndrome.
2. Charcot-Marie-Tooth neural amyotrophy is a hereditary pathology of the myelin sheath. It is distinguished by sensory disturbances, limb dystrophy, spinal deformity and tremor.

This is only a part of the diseases that occur due to the destruction of the myelin layer. The symptoms are the same in most cases. An accurate diagnosis can only be made after computed or magnetic resonance imaging. An important role in the diagnosis is played by the level of qualification of the doctor.

Principles of Treatment of Shell Defects

Diseases associated with the destruction of the pulpy membrane are very difficult to treat. Therapy is aimed mainly at stopping the symptoms and stopping the destruction processes. The earlier the disease is diagnosed, the more likely it is to stop its course.

Myelin Repair Options

Thanks to timely treatment, the process of myelin repair can be started. However, the new myelin sheath will not perform as well. In addition, the disease can go into a chronic stage, and the symptoms persist, only slightly smooth out. But even a slight remyelination can stop the course of the disease and partially restore lost functions.

Modern drugs aimed at regenerating myelin are more effective, but they are very expensive.

Therapy

The following drugs and procedures are used to treat diseases caused by the destruction of the myelin sheath:

• beta-interferons (stop the course of the disease, reduce the risk of relapse and disability);
• immunomodulators (affect the activity of the immune system);
• muscle relaxants (contribute to the restoration of motor functions);

• nootropics (restore conductive activity);
• anti-inflammatory (relieve the inflammatory process that caused the destruction of myelin);
• (prevent damage to brain neurons);
• painkillers and anticonvulsants;
• vitamins and antidepressants;
• CSF filtration (a procedure aimed at cleansing the cerebrospinal fluid).

Disease prognosis

Currently, the treatment of demyelination does not give a 100% result, but scientists are actively developing drugs aimed at restoring the pulpy membrane. Research is carried out in the following areas:

1. Stimulation of oligodendrocytes. These are the cells that make myelin. In an organism affected by demyelination, they do not work. Artificial stimulation of these cells will help start the process of repairing the damaged areas of the myelin sheath.
2. stem cell stimulation. Stem cells can turn into full-fledged tissue. There is a possibility that they can fill the fleshy shell.
3. Regeneration of the blood-brain barrier. During demyelination, this barrier is destroyed and allows lymphocytes to negatively affect myelin. Its restoration protects the myelin layer from attack by the immune system.

Perhaps soon, diseases associated with the destruction of myelin will no longer be incurable.