Microglial and astrocytic change in brains of Creutzfeldt-Jakob disease: an immunocytochemical and quantitative study.
OBJECTIVE
The relationship between microglial cells and astrocytes in brains from patients with Creutzfeldt-Jakob disease (CJD) was immunohistochemically and quantitatively studied.


METHODS
CJD cases, including three with subacute spongiform encephalopathy (SSE), three with panencephalopathic type of CJD (PECJD) and six normal controls were examined. Microglial cells were preferentially labeled by monoclonal anti-KP1 (CD68) antibody and astrocytes by polyclonal anti-glial fibrillary acidic protein (GFAP) antibody. Two cytokines were labeled by polyclonal anti-tumor necrosis factor-alpha (TNF-alpha) and polyclonal interleukin-1alpha (IL1alpha).


RESULTS
In the CJD brains, microglial cell density was significantly higher in the white matter than in the cerebral cortex. In contrast, astrocyte density was significantly higher in the cortex than in the white matter. In the PECJD cases, many hypertrophic microglial cells were clustered along the margin of the demyelinated white matter whereas severely demyelinated white matter contained few microglial cells. The microglial cells were also located in vacuoles in myelinated fibers of the internal capsule in the PECJD cases, which resembled myelinopathic alteration in vacuolar myelopathy. The GFAP-positive astrocytes proliferated much more numerously in the severely demyelinated white matter. The densities of astrocytes and microglial cells showed a significantly negative correlation in the cerebral cortex. The density of the white matter microglia did not differ between the PECJD and SSE cases. TNF-alpha and IL1alpha were expressed by microglial cells, but the TNF-alpha-positive microglial cells were very few in both SSE and PECJD cases. A subset of IL1alpha-positive microglia was found in the SSE case white matter, although the number of KP 1-positive microglial cells greatly surpassed the number of IL1alpha-positive ones.


CONCLUSIONS
These results imply that microglia are increased in number before demyelination and become hypertrophic while phagocytosing myelin in PECJD, and that the negative correlation between the density of microglia and astrocytes is not regulated by either cytokine.
Aoki
T
T
Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.
Kobayashi
K
K
Isaki
K
K
D000328:Adult; D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D017628:Microglia / Q000473:pathology*; D008875:Middle Aged