title: Astrocytes are a specific immunological target in Rasmussen's encephalitis.
abstract: OBJECTIVE
  The current histopathological criteria of Rasmussen's encephalitis (RE) include the presence of T-cell-dominated inflammation, microglial activation, neuronal loss, and astrocytic activation. An in vitro study, however, suggested glutamate receptor 3 (GluR3) antibody-mediated astrocytic loss. Therefore, we investigated astrocytic apoptosis and loss in situ.
  
  
  METHODS
  Histochemical, immunohistochemical, terminal deoxynucleotidyltransferase-mediated biotin-dUTP nick end labeling and in situ hybridization techniques were applied to paraffin sections of 20 RE cases, 6 healthy control subjects, and 6 paraneoplastic encephalomyelitis, 10 Ammon's horn sclerosis, and 5 focal cortical dysplasia cases.
  
  
  RESULTS
  Astrocytic apoptosis and subsequent loss of these cells is a specific feature of RE. Such lesions are not found in the control groups. In RE, astrocytic apoptosis and loss was present both in cortical and in white matter areas. Astrocytes in these tissues showed major histocompatibility complex class I expression. Furthermore, granzyme-B(+) lymphocytes were found in close apposition to astrocytes bordering astrocyte-deficient lesions. Granzyme-B(+) granules in these lymphocytes were polarized and faced the astrocytic membranes. No evidence was found for an antibody-mediated destruction.
  
  
  CONCLUSIONS
  We suggest a specific attack by cytotoxic T lymphocytes as a possible mechanism responsible for astrocytic degeneration in RE. The loss of astrocytes might play a role in neuronal dysfunction, seizure induction, and enhancement of neuronal cell death.
authors.affiliation: Division of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria. jan.bauer@meduniwien.ac.at
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.forename: Volkmar H
authors.initials: VH
authors.lastname: Hans
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000276:immunology* / Q000502:physiology*; D001921:Brain / Q000473:pathology; D002452:Cell Count / Q000379:methods; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007223:Infant; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins