Histology, Myelin


Article Author:
Jake Johnson


Article Editor:
Yasir Al Khalili



Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
5/7/2019 1:48:08 AM

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 boarders 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 are 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]


  • Image 9977 Not availableImage 9977 Not available
    Image courtesy S Bhimji MD
Attributed To: Image courtesy S Bhimji MD

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Histology, Myelin - Questions

Take a quiz of the questions on this article.

Take Quiz
An experimental drug acts on peripheral nervous system myelin to increase the insulation effect, or space constant. Action potentials on the axon would change in what way?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 55-year-old male has a chief complaint of not being able to stand from a seated position. Physical examination revealed bilateral lower extremity weakness with no evidence of cardiovascular compromise. After a thorough neurological exam and history, the patient was diagnosed with Guillain-Barre syndrome. Guillain-Barre syndrome is a demyelinating disease affecting the peripheral nervous system. Which of the following is seen in the myelinated fibers of the peripheral nervous system but is not seen in the central nervous system white matter?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 49-year-old female comes to your clinic complaining of generalized weakness and difficulties following along with presentations at her work due to seeing double. Upon physical examination, there is marked weakness in the lower extremities and grip strength bilaterally. When asked about her family history, she states that her mother was diagnosed with multiple sclerosis and is worried that she may be developing it as well. Which of the following would be expected upon light microscopy of affected tissue in patients with multiple sclerosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
With which of the following would you expect to see a "fried-egg" appearance on a neurological specimen stained with hematoxylin and eosin on light microscopy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
When preparing neurological tissue for electron microscopy, a fixation agent is necessary. Which fixation agent is most commonly used for electron microscopy and why is it used?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Myelin incisures (Schmidt-Lantermann clefts) are a structural component of myelin sheath characterized as pouches of Schwann cell cytoplasm that are left over from the myelination process. What process would be severely impacted if there was a loss of these myelin incisures?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Histology, Myelin - References

References

Salzer JL, Clustering sodium channels at the node of Ranvier: close encounters of the axon-glia kind. Neuron. 1997 Jun;     [PubMed]
Small JR,Ghabriel MN,Allt G, The development of Schmidt-Lanterman incisures: an electron microscope study. Journal of anatomy. 1987 Feb;     [PubMed]
Ghabriel MN,Allt G, The role of Schmidt-Lanterman incisures in Wallerian degeneration. I. A quantitative teased fibre study. Acta neuropathologica. 1979 Nov;     [PubMed]
Möbius W,Nave KA,Werner HB, Electron microscopy of myelin: Structure preservation by high-pressure freezing. Brain research. 2016 Jun 15;     [PubMed]
Fix AS,Garman RH, Practical aspects of neuropathology: a technical guide for working with the nervous system. Toxicologic pathology. 2000 Jan-Feb;     [PubMed]
Miko TL,Gschmeissner SE, Histological methods for assessing myelin sheaths and axons in human nerve trunks. Biotechnic     [PubMed]
Daumas-Duport C,Scheithauer BW,Kelly PJ, A histologic and cytologic method for the spatial definition of gliomas. Mayo Clinic proceedings. 1987 Jun;     [PubMed]
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. Scientific reports. 2018 Mar 5;     [PubMed]
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 research. 1983 Feb 28;     [PubMed]
Compston A,Coles A, Multiple sclerosis. Lancet (London, England). 2008 Oct 25;     [PubMed]
Anderson DW,Ellenberg JH,Leventhal CM,Reingold SC,Rodriguez M,Silberberg DH, Revised estimate of the prevalence of multiple sclerosis in the United States. Annals of neurology. 1992 Mar;     [PubMed]
Fact sheet on Guillain-Barré syndrome (updated October 2016. Releve epidemiologique hebdomadaire. 2017 Feb 3;     [PubMed]
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. Medical hypotheses. 1986 Apr;     [PubMed]
Levitt P,Veenstra-VanderWeele J, Neurodevelopment and the origins of brain disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2015 Jan;     [PubMed]
Barateiro A,Brites D,Fernandes A, Oligodendrocyte Development and Myelination in Neurodevelopment: Molecular Mechanisms in Health and Disease. Current pharmaceutical design. 2016;     [PubMed]
Nave KA,Werner HB, Myelination of the nervous system: mechanisms and functions. Annual review of cell and developmental biology. 2014;     [PubMed]
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 3rd,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) Annals of neurology. 1996 Mar     [PubMed]
Verboon C,van Doorn PA,Jacobs BC, Treatment dilemmas in Guillain-Barré syndrome. Journal of neurology, neurosurgery, and psychiatry. 2017 Apr     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of your specialty. When it is time for the board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study.