A neuroprotective role of microglia in AIDS dementia

来源 :中国神经科学学会第九届全国学术会议暨第五届会员代表大会 | 被引量 : 0次 | 上传用户:yanguangkai
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  Objective To clarify whether the pathologic events of HIV encephalitis and AIDS dementia occur independently in human HIV-1 infection.Methods Twenty brains of patients with HIV-1 infection autopsied in Vienna University were examined by immunohistochemistry and immunofluorescence.Results Eleven cases showed typical pathology of HIV encephalitis in the white mater.Among theses 11 cases, following pathologic changes of the frontal cortex could be observed; diffuse microglial activation in 5 cases, astrocytic gliosis in 5 cases, and apoptosis of glia cells and/or neurons in 6 cases.The other 9 cases had neither HIV encephalitis nor any opportunistic lesions in the brain.In the frontal cortex, however, diffuse microglial activation was observed in 7 cases and astrocytic gliosis in 2 cases.In addition, apparent apoptosis of glia cells could be detected in 1 case.In order to clarify a role of microglial activation in the frontal cortex, we further examined expressions of harmful proinflammatory cytokines, IL-1β and TNF-α, and neuroprotective EAAT-2, which is primarily expressed on astrocytes and keeps extracellular glutamate concentration low in the brain to prevent neurons from excitotoxic cell death.A quantitative analysis of EAAT-2 expression and microglial activation demonstrated that the number of Ibal-positive activated microglia was increased in 12 cases and the area of EAAT-2 expression was declining in 12 cases.There was a significant negative correlation between areas of EAAT-2 expression and numbers of Ibal-positive activated microglia (P<0.01) among the cases with decreased EAAT-2 expression.Expression of proinflammatory cytokines, IL-1β and TNF-α were detected only in microglial nodules, but not in diffusely activated microglia.Conclusion These data indicate that diffuse activation of microglia in the cerebral cortex is independent from HIV encephalitis, and may occur according with reduction of EAAT-2 expression on astrocytes in the brain of AIDS patients.Expression of EAAT-2 by activated microglia suggests its compensatory effect to prevent neurons from glutamate neurotoxicity.
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