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Cell death and birth in multiple sclerosis brain

P Dowling1, W Husar, J Menonna

  • 1Department of Veterans Affairs, New Jersey Health Care System, East Orange 07018, USA.

Journal of the Neurological Sciences
|July 1, 1997
PubMed
Summary
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Multiple sclerosis (MS) pathology involves significant glial cell death, particularly oligodendrocytes, via apoptosis. Despite cell proliferation, glial cell loss dominates, leading to myelin damage in MS lesions.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Multiple sclerosis (MS) is characterized by white matter plaques, myelin destruction, and oligodendrocyte loss.
  • Understanding the role of cell death in MS lesion development is crucial.

Purpose of the Study:

  • To investigate the mechanisms and extent of cell death in active and chronic MS lesions.
  • To determine the specific cell types undergoing death and whether apoptosis or necrosis is the predominant mechanism.

Main Methods:

  • Utilized the in situ TUNEL technique to detect DNA fragmentation indicative of cell death.
  • Employed immunocytochemical co-labeling with glial-specific markers to identify dying cells.
  • Performed confocal microscopy and DNA electrophoresis to characterize cell death mechanisms (apoptosis vs. necrosis).

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  • Assessed cell proliferation using proliferation markers in MS lesions.

    • Main Results:

    • Acute MS lesions showed extensive inflammatory and glial cell death.
    • Chronic MS lesions exhibited ongoing glial cell death, indicating a non-single event attack.
    • 14-40% of dying glial cells were identified as myelin-sustaining oligodendrocytes.
    • TUNEL-positive cells displayed apoptotic nuclear morphology, and MS brain DNA showed an apoptotic ladder.
    • Significant populations of inflammatory and glial cells were found to be proliferating.

    Conclusions:

    • MS pathology involves a dynamic interplay of intense glial cell death, primarily through apoptosis, and robust cellular proliferation.
    • Despite proliferation, overall glial cell loss occurs, contributing to myelin depletion in MS.
    • Apoptosis is suspected as the critical mechanism driving oligodendrocyte loss and subsequent myelin damage in multiple sclerosis.