ABSTRACT
Clear delineation of the nature of neuronal damage is essential to understand the mechanisms of cognitive dysfunction and neurodegeneration in human immunodeficiency virus encephalitis (HIVE). Neurodegeneration of spiny neurons may be mediated by neurotoxins binding to the glutamate receptor followed by abnormal intracellular calcium influx. In the absence of productive viral infection of neuroglial cells, it is likely that neurodegeneration in HIVE is related to an indirect mechanism mediated by the virus infected glial and/or monocytic/microglial cells. Mild cognitive dysfunction, as well as overt dementia, may be related to HIVE-associated neurodegeneration. Depending on the mechanisms responsible for selective neuronal vulnerability in HIVE, the following circuits could be affected: striato-cortical, cortico-cortical, and intrinsic/inhibitory. Neuronal populations affected in the neocortex and basal ganglia characteristically contain dendritic spines and glutamate receptors. A prominent feature of the neurodegenerative changes seen in HIVE and in animal models, is extensive dendritic damage and vacuolization.
