Neuromyelitis optica: a demyelinating disease characterized by acute destruction and regeneration of perivascular astrocytes

Mult Scler. 2010 Oct;16(10):1156-72. doi: 10.1177/1352458510382324. Epub 2010 Sep 7.

Abstract

Background: A serum antibody directed against astrocytes is present in a high proportion of patients with neuromyelitis optica (NMO). The pathogenicity of the antibody is uncertain because no consistent astrocyte lesion is known to occur in NMO.

Objective: To determine whether there is an astrocyte lesion in NMO and if this differs from astrocyte changes in multiple sclerosis (MS).

Methods: Astrocyte pathology in early (still-myelinated) lesions and subacute NMO and MS lesions was examined immunohistochemically and in sections stained for astrocytes using routine histological techniques.

Results: Demyelination in early NMO lesions is accompanied by oligodendrocyte apoptosis in a pattern identical to that seen in MS and this is preceded by an abrupt destruction of perivascular astrocytes. Reparative astrogliosis is effected by a population of unipolar, new astrocytes. Evidence of a different type of astrocyte lesion was found in MS.

Discussion: The findings add to experimental evidence that the antibody is pathogenic. They also raise the possibility that demyelination in MS may be a bystander effect of an astrocyte lesion, i.e. that MS is not a disease primarily of myelin and oligodendrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aquaporin 4 / immunology
  • Astrocytes / pathology*
  • Autopsy
  • Brain / pathology
  • Complement System Proteins / analysis
  • Demyelinating Diseases / pathology*
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Immunoglobulins / analysis
  • Immunohistochemistry
  • Inflammation / pathology
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology
  • Myelin Sheath / metabolism
  • Nerve Regeneration / physiology
  • Neuromyelitis Optica / pathology*
  • Oligodendroglia / pathology
  • Optic Nerve / pathology
  • Paraffin Embedding
  • Spinal Cord / pathology
  • Young Adult

Substances

  • Aquaporin 4
  • Glial Fibrillary Acidic Protein
  • Immunoglobulins
  • Complement System Proteins