Introduction to demyelinating diseases

DR : Hesham Awn
TAIZ 2010

introduction

Glial cells constitutes the large majority of cells in the nervous system. As an overview the number of glial cells increases during evolution ,glial cells constitute 25% of total cells in the drosophila ,65% in Rodents , and 90 % in human brain.

introduction

Virchow (1846) first described that there were cells other than neurons. He thought that it was the connective tissue of the brain ,which he called Nervenkitt (nerve glue) , neuroglia. The name survived , although the original concept radically changed.

introduction

The characterization of the major glial cell type was the result of microscopic studies , and specially the techniques of metallic impregnation developed by Ramon Cajal and Rio Hortege (1913) using gold impregnation ,identified the Astrocyte Among neuronal cells ,as well as third element which was not impregnated by this technique.

Fig. 1.

Baumann, N. et al. Physiol. Rev. 81: 871-927 2001

Copyright 2001 American Physiological Society

introduction

In (1921) ,using silver carbonate impregnation they found tow other cell types ,the oligodendrocyte (interfasicular glia and microglia). The progress of morphological techniques and the discovery of cellular markers by immunocytochemical techniques indicate the of multiple functional macroglial subclasses.

introduction

Glial cells are necessary for correct neuronal development and for the functions of mature neurons. It now seems likely that oligodendrocytes have functions other than those related to Myelin formation and maintenance.

Oligodendrocytes:

The term oligodendroglia was introduced by Rio Hortega (1921), to describe those neurological cells that show few processes in material stained by metallic impregnation techniques.

Oligodendrocytes:

The oligodendrocyte is mainly a myelin forming cell, but there are also satellite oligodendrocytes, who are perineuronal and may serve to regulate the microenvironment around neurons.

Oligodendrocytes:

An oligodendrocyte extends many processes ,each of which contacts and repeatedly envelopes a stretch of axons with subsequent condensation of this multispiral membrane forming myelin . On the same axon, adjusted myelin segments belong to different oligodendrocytes, the number of processes that from myelin sheaths from a single oligodendrocyte varies according to the area of CNS and possibly the species.

myelin

The myelin sheath around most axons constitutes the most abundant membrane structure in the vertebrate nervous system. Its unique composition (richness in lipids and low water content allowing the electrical insullotion of axons ) and its unique segmental structure responsible for the saltatory conduction of nerve impulses allow the myelin sheath to support the fast nerve conduction in the thin fibers in the vertebrate nervous system.

Cont.

High- speed conduction ,fidelity of transfer signaling on long distances ,and space economy are the three major advantages conferred to the vertebrate nervous system by the myelin sheath, in contrast to the invertebrate nervous system where rapid conduction is accompanied by increase axonal calibers.

Cont.

The importance of myelin in human development is highlighted by its involvement in different neurological diseases such as leukodystrophies and multiple sclerosis in the CNS and peripheral neuropathies in PNS.

Cont.

Myelin is the essential constituent of white matter in the CNS which contains a 40-50% myelin on a dry weight basis. Myelin is a poorly hydrated structure containing 40% water in contrast to gray matter 80%. Myelin dry weight consist of 70% lipid and 30% proteins this lipid to proteins ratio is very peculiar to the myelin membrane ,it is generally the reverse in other cellular membrane.

Cont.

The insulating properties of the myelin sheath ,which favor rapid nerve conduction velocity ,are largely due to its structure , its thickness , its low water content , and its richness in lipid.

Disease of myelin
Diseases affecting central nervous system (CNS) myelin can be classified on the basis of whether a primary biochemical abnormality of myelin exist (dysmyelinating) or whether some other process damages the myelin or oligodendroglia cell (demyelinating )

Dysmyelinating diseases:
Include several hereditary disorders: adrenoleukodystrophy. metachromic leukodystrophy. krabbes disease . Alexanders disease. Canavan-Von Baaert-Bertrand disease. Pelizaeus-Merzbacher disease. Phenylketonuria.

Demyelinating disease :
Autoimmune: Acute dissemenated encephalomyelitis (ADEM) Acute hemorrhagic leukoencephalopayh. Multiple sclerosis. Infectious: progressive multifocal leukoencephalopathy (PML).

Cont.
Toxic / metabolic: Carbon monoxide. Vitamin B12 deficiency. Mercury intoxication. Alcohol /tobacco amblyopia. Central pontine myelination. Marchiafava Biqnami syndrome. Hypoxia. Radiation.

Cont.
Vascular: Binswangers disease. CADASIL.