Nitric oxide synthase expression and apoptotic cell death in brains of AIDS and AIDS dementia patients

Objectives: To determine the occurrence and cellular localization of induci ble nitric oxide synthase (iNOS), NOS activity and its association with cel l death in brains of AIDS and AIDS dementia complex (ADC) patients. Design and methods: Post-mortem cerebral cortex tissue of eight AIDS patien ts, eight ADC patients and eight control subjects was processed for iNOS im munocytochemistry, NADPH-diaphorase activity staining as an index of NOS ac tivity, and in situ end-labelling to detect cell death. Results: iNOS-positive cells were present in the white matter of 14 out of 16 AIDS and ADC patients, whereas two out of eight control subjects showed iNOS-positive cells. iNOS immunoreactivity was exclusively localized in act ivated macrophages and microglial cells that both showed NADPH-diaphorase a ctivity. In addition, NADPH-diaphorase activity, not related to iNOS immuno reactivity, was observed in astrocytes in both white and grey matter of AID S and ADC patients. All AIDS and ADC patients, and only one control subject showed characteristic Features of apoptotic cell death. Conclusions: Different forms of NOS are present in microglial cells and ast rocytes of AIDS and ADC patients but are largely absent in control subjects . Although more NOS-expressing cells occur in ADC than in AIDS patients, ap optotic cell death was found in both patient groups to the same extent. We postulate that NO production in brains of AIDS patients results in cumulati ve cortical cell loss, which becomes neurologically evident at later stages of disease and is expressed as ADC. (C) 1999 Lippincott Williams & Wilkins .