Astrocytes are a specific immunological target in Rasmussen's encephalitis.
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.
Bauer
Jan
J
Division of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria. jan.bauer@meduniwien.ac.at
Elger
Christian E
CE
Hans
Volkmar H
VH
Schramm
Johannes
J
Urbach
Horst
H
Lassmann
Hans
H
Bien
Christian G
CG
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
D009419:Nerve Tissue Proteins