Structure-specific glial response in a macaque model of neuroAIDS: multivoxel proton magnetic resonance spectroscopic imaging at 3 Tesla.
OBJECTIVE
As ~40% of persons with HIV also suffer neurocognitive decline, we sought to assess metabolic dysfunction in the brains of simian immunodeficiency virus (SIV)-infected rhesus macaques, an advanced animal model, in structures involved in cognitive function. We test the hypothesis that SIV-infection produces proton-magnetic resonance spectroscopic imaging (H-MRSI)-observed decline in the neuronal marker, N-acetylaspartate (NAA), and elevations in the glial marker, myo-inositol (mI), and associated creatine (Cr) and choline (Cho) in these structures.


METHODS
Pre- and 4-6 weeks post-SIV infection (with CD8 T-lymphocyte depletion) was monitored with T2-weighted quantitative MRI and 16×16×4 multivoxel H-MRSI (TE/TR = 33/1400 ms) in the brains of five rhesus macaques.


METHODS
Exploiting the high-resolution H-MRSI grid, we obtained absolute, cerebrospinal fluid partial volume-corrected NAA, Cr, Cho and mI concentrations from centrum semiovale, caudate nucleus, putamen, thalamus and hippocampus regions.


RESULTS
Pre- to post-infection mean Cr increased in the thalamus: 7.2±0.4 to 8.0±0.8 mmol/l (+11%, P<0.05); mI increased in the centrum semiovale: 5.1±0.8 to 6.6±0.8 mmol/l, caudate: 5.7±0.7 to 7.3±0.5 mmol/l, thalamus: 6.8±0.8 to 8.5±0.8 mmol/l and hippocampus: 7.7±1.2 to 9.9±0.4 mmol/l (+29%, +27%, +24% and +29%, all P<0.05). NAA and Cho changes were not significant.


CONCLUSIONS
SIV-infection appears to cause brain injury indirectly, through glial activation, while the deep gray matter structures' neuronal cell bodies are relatively spared. Treatment regimens to reduce gliosis may, therefore, prevent neuronal damage and its associated neurocognitive impairment.
aDepartment of Radiology, New York University School of Medicine, New York, New York bMassachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging and Neuroradiology Division, Charlestown, Massachusetts, USA.
William E
WE
Wu
Assaf
A
Tal
Ke
K
Zhang
James S
JS
Babb
Eva-Maria
EM
Ratai
R Gilberto
RG
González
Oded
O
Gonen
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001923:Brain Chemistry; D002493:Central Nervous System Diseases / Q000473:pathology*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002794:Choline / Q000032:analysis; D003401:Creatine / Q000032:analysis; D005260:Female; D007294:Inositol / Q000032:analysis*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000473:pathology*
D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline