Apoptotic neurons in brains from paediatric patients with HIV‐I encephalitis and progressive encephalopathy

The pathogenesis of human immunodeficiency virus type 1 (HIV‐1) associated dementia in adults involves neuronal loss from discrete areas of the neocortex and subcortical regions, but the mechanism for neuronal death is poorly understood. Gene‐directed cell death resulting in apoptosis is thought to be a normal feature of neuronal development, but little is known about neuronal apoptosis in disease states. We investigated whether HIV‐1 infection of the central nervous system is spatially associated with apoptosis of neurons. Using an in situ technique to identify newly cleaved 3′‐OH ends of DNA as a marker for apoptosis, we demonstrate the presence of apoptotic neurons in cerebral cortex and basal ganglia of children that had HIV‐1 encephalitis with progressive encephalopathy. Furthermore, an association was observed between the localization of apoptotic neurons and perivascular inflammatory cell infiltrates containing HIV‐1 infected macrophages and multinucleated giant cells. Apoptotic neurons and p24–positive macrophages were observed infrequently in cerebral cortex and basal ganglia in children with HIV‐1 infection without encephalitis or clinical encephalopathy. In nine control (HIV‐1 negative) brains, ranging from the first post‐natal month of life to 16.5 years of age, infrequent neuronal apoptosis was observed in three cases. These findings suggest that neuronal apoptosis is unlikely to be associated with post‐natal development except in early post‐natal germinal matrix, and that it may instead represent the end result of specific pathological processes, such as HIV‐1 encephalitis.