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Background:  Neuroglial dysfunction is thought to be one of the pathogenic factors contributing to HIV dementia (HIV⁺D). The purpose of this study was to characterize the profile and magnitude of neuroglial reactions in brain tissues from HIV⁺D patients as compared with HIV seropositive (HIV⁺ND) and seronegative controls (HIV^–ND) by immunocytochemical and unbiased quantitative techniques.

Methods:  Brain samples from middle frontal gyrus, deep white, and basal ganglia were obtained at autopsy from HIV⁺D (n = 10), HIV⁺ND (n = 10), and HIV^–ND (n = 10) patients. Neuroglial reactions were assessed by immunocytochemistry with markers for MHC class II (activated microglia) and GFAP (astrocytes). An unbiased assessment of the area fraction of immunoreactivity was used to quantify the magnitude of neuroglial reactions. Western blot analysis was also used to evaluate the expression of GFAP. Proliferation of neuroglia was assessed by Ki-67 immunostaining. Group comparisons were carried out using bootstrap linear multiple regressions and Mann-Whitney rank sum tests where appropriate.

Results:  Microglial activation in the middle frontal gyrus (p < 0.001) and basal ganglia (p < 0.01) was the most significant neuroglial reaction observed in patients with HIV⁺D as compared with HIV^–ND, however no significant differences were found between HIV-infected patients with and without dementia. There was no evidence of increase in the fraction of immunoreactivity for astrocytes in HIV^–D or HIV⁺ ND nor was there evidence of proliferation by Ki-67 immunostaining. A separate analysis of the pattern of neuroglial reactions between HIV⁺D with and without encephalitis revealed that the overall magnitude of neuroglial reactions were similar and predominance of multinucleated giant cell formation was the only defining neuropathological feature.

Conclusions:  This study supports the hypothesis that marked microglia activation in the brain is a commonly seen reaction in the central nervous system of patients with AIDS, but it did not establish differences in neuroglial activation between HIV⁺D and HIV⁺ND patients. Even though there is no evidence of neuroglial proliferation HIV⁺ cases, astrocytes in HIV⁺D and HIV⁺ND had morphological evidence of activation. These findings support the central role of neuroglial activation and dysfunction in neurological complications of AIDS such as HIV⁺D.

Keywords: HIV dementia; neuropathology; neuroglia