Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS.
In vivo MR spectroscopy (MRS) studies have shown reductions in NAA/Cr levels in patients with severe neurocognitive deficits due to AIDS dementia complex (ADC), also known as neuroAIDS. The relationship between the cellular changes within the brain during neuroAIDS and the role of NAA/Cr as a metabolic marker remains unclear. In order to clarify the relationship between NAA/Cr and disease severity we utilized the simian immunodeficiency virus (SIV)/macaque model of encephalitis. High-field proton MRS was performed on extracted metabolites from frontal cortex tissue samples of 29 rhesus macaques (6 healthy, 23 moribund with AIDS). Neuropathologic determination of encephalitis severity for each animal was completed and was found to correlate with NAA/Cr levels. Decreases in Glu/Cr and GABA/Cr may indicate that both excitatory and inhibitory neurons are affected. Highly significant correlations between NAA/Cr, Glu/Cr, and GABA/Cr were observed. These neuronal metabolites were also decreased in the absence of classical SIV encephalitis (SIVE). At any disease classification, animals inoculated with SIVmac251 were found to have lower levels of NAA/Cr than animals inoculated with SIVmac239. In considering therapy for neuroAIDS the findings here support prevention of the encephalitic process, but suggest that suppressing the formation of multinucleated giant cells alone would be insufficient to prevent neuronal injury.
Lentz
Margaret R
MR
Massachusetts General Hospital, Department of Neuroradiology, Boston, Massachusetts 02114-2696, USA.
Westmoreland
Susan V
SV
Lee
Vallent
V
Ratai
Eva-Maria
EM
Halpern
Elkan F
EF
González
R Gilberto
RG
D015526:AIDS Dementia Complex / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism*; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D016014:Linear Models; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D012720:Severity of Illness Index; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline; D005998:Glycine