Histology, Myelin – StatPearls – NCBI Bookshelf

Jake H. Johnson; Yasir Al Khalili.

Author Information and Affiliations

Last Update: May 1, 2023.

Introduction

Myelin sheath is a fatty product formed from specific neuroglial cells that provides numerous vital supporting functions as well as increases the rate of conduction of action potentials for some central and peripheral nervous system neurons. An axon wrapped in myelin sheath is said to be myelinated fibers, as such, axons not wrapped in myelin are non-myelinated fibers. In the central nervous system, the myelinated fibers have the collective name of white matter, and the nonmyelinated fibers are collectively known as gray matter as they look white and gray respectively on gross inspection of the brain in sagittal cross-section. Myelin is formed via oligodendrocytes and Schwann cells in the central and peripheral nervous systems respectively. Many physiologic complications and clinical symptoms can arise from the malformation and destruction of myelin.

Structure

Myelin is known for having several structural features, most notably, the nodes of Ranvier and myelin incisures (Schmidt-Lantermann clefts). The nodes of Ranvier are the region where two adjacent myelin segments meet and allow for saltatory conduction to occur. Myelin incisures are pouches of Schwann cell cytoplasm, left over from the myelination process, and are believed to play a major role in Wallerian degeneration.[1][2][3]

Function

In both peripheral and central nervous systems, myelin plays a crucial role in the protection and conduction of many neurons. Myelin sheath acts as an insulator allowing for protection of the integrity of the nerve impulse as well as protecting the axon from foreign electrical impulses. Myelin also yields the formation of the nodes of Ranvier which allow for saltatory conduction and faster propagation of action potentials to occur.[4]

Tissue Preparation

Historically, an aldehyde fixation was used to fix the nervous tissue for use in electron microscopy. Today, histological fixing of the nervous tissue is commonly done via a high-pressure freezing technique which yields a better-contrasted specimen as well as better preservation of the nervous tissue with fewer artifacts due to better fixation. However, aldehydes, such as formalin, are still used as a fixation solution for purposes of light microscopy as the decreased contrast, and inferior preservation of the tissue is negligible for use in routine nervous tissue studies.[5][6]

Histochemistry and Cytochemistry

In the central nervous system, myelin can undergo assessment via the use of anti-proteolipid protein and anti-myelin basic protein immunohistochemical stains; this is because both the myelin basic protein and proteolipid protein are present in oligodendrocytes as well as myelin sheath in the central nervous system.[7]

Microscopy, Light

Myelin can be seen using light microscopy using various histological methods, such as but not limited to: hematoxylin and eosin, Luxol fast blue and plastic (paraffin) embedding. These histological methods pronounce myelin and typically makes it appear as peripheral rings surrounding an axon when looking at a transverse section and as long parallel projections when viewing a longitudinal section. The nuclei of oligodendrocytes and Schwann cells are visible on hematoxylin & eosin staining; this presents as circular basophilic nuclei with a perinuclear halo giving a “fried-egg” appearance and as longitudinal basophilic nuclei proximal to an axon respectively. Light microscopy is one of the most commonly used methods used to assess the presence of specific pathology in nervous tissue.[8][9]

Microscopy, Electron

Myelin can be seen on transmission electron microscopy typically as a thick dark outline surrounding myelinated nerve fibers. In research, the use of three-dimensional electron microscopy can be used to view various injuries and disease processes related to the myelin sheath. This technique is typically not used clinically but has prospects to be advantageous to further the understanding of various pathophysiologic processes. [5][10]

Pathophysiology

Myelin sheath formation initiates in the CNS of the human embryo at about four months gestation. Oligodendrocytes can myelinate multiple axons at the same time (up to 50), and as such, any given myelinated neuron in the central nervous system can undergo myelination by several oligodendrocytes. Myelination of neurons in the peripheral nervous system commences between the twelfth and eighteenth week of gestation. Unlike oligodendrocytes, Schwann cells surround only a single axon. Schwann cells also play a role in peripheral neuron regeneration after an injury.

Disruptions of myelin sheath formation and/or autoimmune-related destruction of myelin sheath can often lead to serious neurological complications. These disruptions are commonly referred to as demyelinating diseases. The most common demyelinating disease is multiple sclerosis. Multiple sclerosis is an autoimmune disorder with the patients’ own antibodies directing their efforts against the myelin sheath in their central nervous system. Multiple sclerosis has a prevalence of about one in every thousand persons in the United States with women being affected with the disease two times as much as men. Histologically, multiple sclerosis shows abrupt edges of demyelinated plaque when stained with specific myelin stains. More specifically, light microscopy can view active plaques, in which there is active and progressive demyelination with PAS-stain positive breakdown product and lipid-rich macrophages present, as well as inactive plaques, in which there is no active demyelination taking place, and thus no myelin or myelin degradation products are found. That said, in inactive plaques, there is a reduction of oligodendrocytes nuclei, and there’s an increase in astrocytic proliferation. The third type of plaques seen in multiple sclerosis patients demonstrates non-abrupt borders between the normal and demyelinated tissue. These “shadow plaques” are theorized to be due to oligodendrocytes that did not get destroyed and that partially re-myelinate the damaged tissue.

Multiple sclerosis typically presents clinically with visual disturbances such as diplopia and monocular blindness as well as peripheral symptoms of muscle weakness, sensory deficits, and subsequently ataxia.

The cause of multiple sclerosis remains unknown. However, there has been a higher prevalence of multiple sclerosis in regions more north of the equator than those close or south of the equator; this leads many researchers to believe there’s a genetic and environmental component. Guillain-Barre syndrome is another demyelinating disorder, but unlike multiple sclerosis, there is autoimmune destruction of the myelin sheath in the peripheral nervous system as opposed to the central nervous system.

Guillain-Barre is rarer than multiple sclerosis, only affecting one in every one hundred thousand persons every year and affects males and females equally.[11][12][13] Guillain-Barre syndrome typically presents as an ascending paralysis and muscle weakness, with it’s most severe and life-threatening complication being respiratory depression. The cause of Guillain-Barre disease is also not yet known, but triggers include microbial infection, traumatic surgery, or, very rarely, vaccination.[14][15][16]

Clinical Significance

Demyelinating diseases such as multiple sclerosis and Guillain-Barre syndrome have a progressive and devastating effect on affected patients. There has not been an approved treatment to reverse the demyelinating process in these diseases. However, there is an array of medications that can be used to slow the progression and to treat the symptoms that may arise from them. That said, these medications are not without potential shortfalls and side-effects. For example, beta interferons are commonly prescribed to the patients to help slow the progression of disease in multiple sclerosis. However, the use of beta interferons have been shown to induce flu-like symptoms as well as liver damage, but it is still widely used in many patients due to the therapeutic effects of the drug outweighing its potential adverse side-effects. [17][18]

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Figure

Nerve cell. Image courtesy S Bhimji MD

References

1.

Salzer JL. Clustering sodium channels at the node of Ranvier: close encounters of the axon-glia kind. Neuron. 1997 Jun;18(6):843-6. [PubMed: 9208851]

2.

Small JR, Ghabriel MN, Allt G. The development of Schmidt-Lanterman incisures: an electron microscope study. J Anat. 1987 Feb;150:277-86. [PMC free article: PMC1261681] [PubMed: 3654340]

3.

Ghabriel MN, Allt G. The role of Schmidt-Lanterman incisures in Wallerian degeneration. I. A quantitative teased fibre study. Acta Neuropathol. 1979 Nov;48(2):93-93. [PubMed: 506700]

4.

Nave KA, Werner HB. Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol. 2014;30:503-33. [PubMed: 25288117]

5.

Möbius W, Nave KA, Werner HB. Electron microscopy of myelin: Structure preservation by high-pressure freezing. Brain Res. 2016 Jun 15;1641(Pt A):92-100. [PubMed: 26920467]

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Fix AS, Garman RH. Practical aspects of neuropathology: a technical guide for working with the nervous system. Toxicol Pathol. 2000 Jan-Feb;28(1):122-31. [PubMed: 10668998]

7.

Mithen FA, Wood PM, Agrawal HC, Bunge RP. Immunohistochemical study of myelin sheaths formed by oligodendrocytes interacting with dissociated dorsal root ganglion neurons in culture. Brain Res. 1983 Feb 28;262(1):63-9. [PubMed: 6187412]

8.

Miko TL, Gschmeissner SE. Histological methods for assessing myelin sheaths and axons in human nerve trunks. Biotech Histochem. 1994 Mar;69(2):68-77. [PubMed: 8204769]

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Daumas-Duport C, Scheithauer BW, Kelly PJ. A histologic and cytologic method for the spatial definition of gliomas. Mayo Clin Proc. 1987 Jun;62(6):435-49. [PubMed: 2437411]

10.

Giacci MK, Bartlett CA, Huynh M, Kilburn MR, Dunlop SA, Fitzgerald M. Three dimensional electron microscopy reveals changing axonal and myelin morphology along normal and partially injured optic nerves. Sci Rep. 2018 Mar 05;8(1):3979. [PMC free article: PMC5838102] [PubMed: 29507421]

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Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. [PubMed: 18970977]

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Anderson DW, Ellenberg JH, Leventhal CM, Reingold SC, Rodriguez M, Silberberg DH. Revised estimate of the prevalence of multiple sclerosis in the United States. Ann Neurol. 1992 Mar;31(3):333-6. [PubMed: 1637140]

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Fact sheet on Guillain-Barré syndrome (updated October 2016. Wkly Epidemiol Rec. 2017 Feb 03;92(5):50-2. [PubMed: 28155266]

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Sharpe RJ. The low incidence of multiple sclerosis in areas near the equator may be due to ultraviolet light induced suppressor cells to melanocyte antigens. Med Hypotheses. 1986 Apr;19(4):319-23. [PubMed: 2940440]

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Levitt P, Veenstra-VanderWeele J. Neurodevelopment and the origins of brain disorders. Neuropsychopharmacology. 2015 Jan;40(1):1-3. [PMC free article: PMC4262917] [PubMed: 25482168]

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Barateiro A, Brites D, Fernandes A. Oligodendrocyte Development and Myelination in Neurodevelopment: Molecular Mechanisms in Health and Disease. Curr Pharm Des. 2016;22(6):656-79. [PubMed: 26635271]

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Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Granger CV, Simon JH, Alam JJ, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munschauer FE, Priore RL, Pullicino PM, Scherokman BJ, Whitham RH. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996 Mar;39(3):285-94. [PubMed: 8602746]

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Verboon C, van Doorn PA, Jacobs BC. Treatment dilemmas in Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):346-352. [PubMed: 27837102]

Disclosure: Jake Johnson declares no relevant financial relationships with ineligible companies.

Disclosure: Yasir Al Khalili declares no relevant financial relationships with ineligible companies.

Does the Myelin Sheath Play a Role in MS?

What is the myelin sheath?

Function

Link to MS

Causes of damage

Regeneration

FAQs

Multiple sclerosis (MS) is a disorder in which the body’s immune system attacks healthy parts of the central nervous system — the brain, spinal cord, and optic nerves. This inflammatory attack causes damage to the myelin sheath, a critical part of nerve cells.

What is the myelin sheath?

Nerve cells, known as neurons, are the cells in the nervous system responsible for sending electrical signals that govern body movements and give rise to thoughts and emotions. Each neuron contains a long fiber-like projection, called an axon.

When a neuron “fires,” an electrical current travels from one end of the axon to the other. Once it reaches the end, the electrical impulse triggers the neuron to release chemical messengers called neurotransmitters to pass the signal to other cells (for example, prompting a muscle to contract).

The myelin sheath is a coating surrounding axons, which are the nerve fibers. It is composed mainly of fatty molecules (lipids), as well as a number of specialized proteins. The sheath has a characteristic structure, with regions densely wrapped in myelin interspersed with areas of little to no myelin (referred to as the nodes of Ranvier).

In addition to neurons, the nervous system also is home to a diverse class of cells called glia, which play a number of roles to support neuronal function. Myelin in the central nervous system is primarily made by glial cells called oligodendrocytes.

How does the myelin sheath function?

The most well-characterized role of the myelin sheath is in helping neurons to send electrical signals faster. Conceptually, the myelin sheath wrapped around an axon is a bit like insulation coating a metal wire — just as rubber around a copper wire helps to insulate and direct electricity through the wire, myelin helps insulate and direct electrical signals through nerves.

The biophysics of this process are complicated and not entirely understood, but myelin’s structure is known to play a key role. When an axon does not have myelin, an electrical impulse needs to travel down the entire length of the axon in one go. By contrast, when an axon is wrapped in myelin, electrical signals can “skip” across the segments of dense myelin and travel across the areas with less myelin (the nodes of Ranvier), allowing the signal to travel faster.

It was long thought that this electricity-enhancing effect was the only role of myelin, but in recent years, research has shown that the myelin sheath actually has numerous other functions helping to maintain neuronal health. For example, the myelin sheath helps to support the metabolic activity of nerve cells, and it is important for regulating salt and water levels in the cell.

How is the myelin sheath linked to MS?

In MS, the immune system launches an inflammatory attack in the central nervous system. This inflammation leads to demyelination — the deterioration and loss of the myelin sheath — and causes damage to axons. Consequently, this leads to the development of lesions in the central nervous system where the tissue is damaged and scarred.

These lesions, which can be visualized on MRI scans, are actually how MS gets its name: The disease is characterized by “multiple” areas of scarring, or “sclerosis.”

MS is one of the most common demyelinating disorders that affect myelin in the central nervous system. As a result of this damage, nerve cells are not able to send electrical signals as efficiently; this impaired neuronal activity is mainly responsible for the symptoms of MS.

What causes damage to the myelin sheath?

It is not known exactly what prompts the start of the inflammatory attack that drives MS, and many interconnecting risk factors — including genetics, lifestyle habits, and environmental exposures — are known to contribute to the development of the disease.

The inflammatory attack itself involves the activity of many types of immune cells, including T-cells and B-cells.

• T-cells are immune cells equipped with specific receptors that can recognize a single molecule (usually a piece of a virus or bacteria). MS is commonly characterized by inflammatory T-cells, which are autoreactive against components of myelin.
• B-cells are best known as the cells that make immunological proteins called antibodies or immunoglobulins. It is common for people with MS to have high levels of antibodies in their cerebrospinal fluid (the liquid around the brain and spinal cord), and testing for these antibodies — a procedure called oligoclonal banding — may help in diagnosing MS.

Other immune cells involved in the MS-driving attack include dendritic cells and macrophages, which can secrete signaling molecules that promote inflammation. Dysregulated activity of glial cells, including microglia and astrocytes, also is involved in the attack.

Does the myelin sheath regenerate?

If myelin is damaged or destroyed, it can be repaired or replaced — a process referred to as remyelination.

Remyelination is done mainly by myelin-making oligodendrocytes, including mature oligodendrocytes that reside in the nervous system and new oligodendrocytes generated via the activation of immature cells called oligodendrocyte progenitor cells (OPCs).

While myelin repair in the body is possible, it is not very efficient — remyelination generally decreases with increasing age, and the inflammation that drives MS can further interfere with the process.

Finding therapeutic strategies that can promote remyelination is an ongoing area of research. Dozens of potential remyelinating treatments have shown promise in laboratory studies, and a few medications have shown positive results in early clinical studies in people with MS or other conditions associated with myelin loss.

Some of the potential remyelinating treatments being tested in MS clinical trials include:

• metformin and clemastine
• NVG-291
• CNM-Au8
• PIPE-307

A number of disease-modifying therapies have been developed for MS, mainly to reduce ongoing inflammation. Whether some of these medications also may act to promote myelin repair is still debatable.

Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Demyelinating diseases – Neurology with manual therapy – Departments

Demyelinating disease (DZ) is a collective concept that implies the development of pathological processes caused by a violation of the sheaths of myelin fibers. Both trauma and complication of infectious pathology can provoke a disease of such pathogenesis. The negative impact of allergic reactions is not excluded.

The clinical picture includes symptoms of dysfunction of various body systems: gastroenterological symptoms, memory impairment, cognitive impairment, hand tremor, etc. may be present. At the initial stage of the development of the disease, the clinic, as a rule, is absent.

Demyelinating diseases of the nervous system can occur at any age: they are equally diagnosed in children and adults. Diagnosis is carried out by physical examination, laboratory and instrumental research methods. The volume of examinations is carried out in accordance with international standards for the provision of medical care.

Main symptoms:

• headache
• mood swings
• speech disorder
• convulsions
• memory violation
• Urinary incontinence
• decreased vision
• blood pressure fluctuations
• behavior changes
• paralysis
• trembling fingers
• mental impairment
• visual hallucinations
• auditory hallucinations
• difficulty in swallowing
• poor orientation in space
• immobility of the eyeballs
• skin desensitization
• violation of the synchronism of movements.

Etiology

DZ of the brain and spinal cord can be caused by the following etiological factors – alcohol poisoning, psychotropic substances, infectious diseases, multiple sclerosis, and the following pathological processes – infectious and inflammatory diseases with frequent relapses, multiple sclerosis, prolonged bacterial infections, intoxication heavy metals, Phos poisoning, chronic fatigue syndrome, nervous experiences, systemic diseases of various etiologies, against the background of spinal cord injury.

Classification

DZ – the classification of such a disease implies the division of the pathological process into two large groups: myelinopathy , in which the destruction of abnormal myelin occurs, and myelinoclasia – in this case, the destruction of normal myelin. As for localization, the disease can affect the brain, central nervous system, spinal cord.

Symptoms

The nature of the course of the clinical picture will depend on which area of ​​the brain or central nervous system the pathological process develops, and what caused it.

Diagnosis

It is determined by a neurologist, it is impossible to determine DZ only by the nature of the course. First of all, the doctor conducts a physical examination of the patient, uses laboratory and instrumental methods: clinical and detailed biochemical blood tests, magnetic resonance imaging, magnetic resonance imaging using contrast substances.

Treatment is determined by the doctor, self-medication is not allowed.

Prevention

Preventive recommendations are to prevent those diseases that are included in the etiological list, in addition, people who are at risk, that is, have had previous diseases of the central nervous system or the brain / spinal cord, should systematically undergo a medical examination.

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Demyelinating diseases are a group of pathological processes that are characterized by damage to neurons of the spinal cord and brain due to the destruction of their myelin sheath (a specific structure that performs a barrier function and is responsible for the speed of transmission of nerve impulses).

Class

Practitioners divide the processes of demyelination of nerve fibers into:

1. Myelinopathy caused by a congenital anomaly of the biochemical structure of myelin. As a result of such a genetic disorder, the immune system mistakes the abnormal substance for a pathogen and produces specific antibodies aimed at destroying it.
2. Myelinoclasty – in this case, autoimmune antibodies destroy normal myelin under the influence of certain exogenous (external) factors.

Causes of development

Demyelinating process can be caused by:

• poisoning with alcohol, heavy metals, chemical or psychotropic substances;
• multiple sclerosis;
• severe infectious and inflammatory diseases;
• constant psycho-emotional stress;
• systemic pathologies;
• spinal cord injuries;
• chronic fatigue syndrome.

Symptoms and first signs

Clinical manifestations of demyelinating diseases depend on the localization of the pathological process. The collective symptom-complex is characterized by:

• tremor of the upper extremities;
• dizziness;
• blood pressure instability;
• headaches;
• deterioration in visual acuity and memory;
• disorientation;
• impaired speech and movement synchrony;
• visual and auditory hallucinations;
• emotional instability;
• psycho-type change;
• involuntary urination and defecation;
• convulsive attacks;
• paresis;
• decreased sensitivity in certain parts of the body and cognitive abilities.

The progression of the demyelination process leads to the fact that the patient becomes completely helpless, in need of constant nursing care.

Diagnostic methods

For the timely detection of the pathological process occurring in the myelin sheath, the following results are used:

1. Family and personal anamnesis.
2. Careful examination of the patient.
3. Computed tomography and nuclear magnetic resonance imaging to assess the state of the brain.
4. Magnetic resonance imaging with the use of a contrast agent – to determine the nature of neuronal damage and assess the severity of pathological changes.
5. Clinical urinalysis – to assess the state of the urinary capacity of the kidneys.
6. Hemograms – for assessing the state of the hematopoietic system.
7. Serological screening – to detect and quantify autoimmune antibodies.
8. Blood gas analysis.
9. Coagulograms – to determine blood clotting factors.
10. Biochemical blood testing – for measuring the concentration of: electrolyte ions, glucose, total protein and its fractions, digestive enzymes, total and direct bilirubin, thyroid hormones, cholesterol, triglycerides, high and low density lipoproteins.

Treatment

Patients with demyelinating diseases are prescribed:

• taking antibacterial, analgesic and non-steroidal anti-inflammatory drugs, nootropics, muscle relaxants, immunomodulators, corticosteroids, multivitamins;
• physiotherapy exercises;
• manual therapy;
• mud treatment;
• acupuncture;
• reflexology;
• massage.