Cytopathologic and neurochemical correlates of progression to motor/cognitive impairment in SIV-infected rhesus monkeys.
Neurochemical, pathologic, virologic, and histochemical correlates of simian immunodeficiency virus (SIV)-associated central nervous system (CNS) dysfunction were assessed serially or at necropsy in rhesus monkeys that exhibited motor and cognitive deficits after SIV infection. Some infected monkeys presented with signs of acquired immunodeficiency disease (AIDS) at the time of sacrifice. Seven of eight animals exhibited motor skill impairment which was associated with elevated quinolinic acid in cerebrospinal fluid (CSF). Examination of the brains revealed diffuse increases in glial fibrillary acidic protein immunoreactivity in cerebral cortex in all animals, regardless of evidence of immunodeficiency disease. Reactive astrogliosis preceded or was coincident with the onset of neuropsychological impairments. Virus rescue from CSF of six of eight infected animals showed that one of three animals with AIDS and none of three animals without AIDS at necropsy had virus rescue-positive CSF. Multinucleated giant cells were seen in the brain of only one animal with end-stage AIDS and high systemic virus burden at death. Neither systemic nor CNS virus burden was associated with the onset of CNS dysfunction. SIV-associated motor/cognitive impairment is associated with subtle, widespread changes in CNS cytology and neurochemistry, rather than with large increases in brain virus burden or widespread virus-associated brain lesions.
Rausch
D M
DM
Section on Molecular Neuroscience, Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892.
Heyes
M P
MP
Murray
E A
EA
Lendvay
J
J
Sharer
L R
LR
Ward
J M
JM
Rehm
S
S
Nohr
D
D
Weihe
E
E
Eiden
L E
LE
D000818:Animals; D001921:Brain / Q000382:microbiology / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D008253:Macaca mulatta; D008297:Male; D009043:Motor Activity; D017378:Quinolinic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000503:physiopathology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification; D013116:Spinal Cord / Q000382:microbiology / Q000473:pathology*
D005904:Glial Fibrillary Acidic Protein; D017378:Quinolinic Acid