Early brain injury in the SIV-macaque model of AIDS.
OBJECTIVE
To specify the type and severity of cellular damage in the central nervous system soon after infection and at later stages of disease in the SIV-macaque model of AIDS.


METHODS
Adjacent samples of frontal cortical gray matter were taken from three groups of macaques: uninfected controls (n = 4), acute (14 days post-infection; n = 4), and chronic (mean 2 years post-infection; n = 7). In vitro high resolution magnetic resonance spectroscopy of snap frozen intact tissue and quantitative neuropathology measurements of synaptophysin, calbindin, and glial fibrillary acidic protein (GFAP) in formalin-fixed tissue were performed.


RESULTS
Losses in n-acetylaspartate and calbindin (indicating neuronal injury and/or death) and decreases in synaptophysin immunoreactivity (indicating synaptodendritic injury) were detected along with increases in GFAP (indicating reactive gliosis). Cellular injury worsened progressively with increased time after infection.


CONCLUSIONS
These results are the first direct evidence that neuronal injury occurs soon after infection. The exacerbation of injury with time suggests a connection between the early response of the central nervous system and dementia, which occurs late in the course of infection. This connection may have broad implications for the study of and the development of therapies for damage of the central nervous system by HIV.
González
R G
RG
Neuradiology Division, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Cheng
L L
LL
Westmoreland
S V
SV
Sakaie
K E
KE
Becerra
L R
LR
Lee
P L
PL
Masliah
E
E
Lackner
A A
AA
D015526:AIDS Dementia Complex / Q000473:pathology* / Q000503:physiopathology; D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology* / Q000503:physiopathology
D009419:Nerve Tissue Proteins