title: Global gray and white matter metabolic changes after simian immunodeficiency virus infection in CD8-depleted rhesus macaques: proton MRS imaging at 3 T.
abstract: To test the hypotheses that global decreased neuro-axonal integrity reflected by decreased N-acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo-inositol (mI), present in a CD8-depleted rhesus macaque model of HIV-associated neurocognitive disorders. To this end, we performed quantitative MRI and 16 × 16 × 4 multivoxel proton MRS imaging (TE/TR = 33/1400 ms) in five macaques pre- and 4-6 weeks post-simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125 cm(3) spatial resolution over ~35% of the brain) using linear regression. Pre- to post-infection global WM NAA declined 8%: 6.6 ± 0.4 to 6.0 ± 0.5 mM (p = 0.05); GM Cho declined 20%: 1.3 ± 0.2 to 1.0 ± 0.1 mM (p < 0.003); global mI increased 11%: 5.7 ± 0.4 to 6.5 ± 0.5 mM (p < 0.03). Global GM and WM brain volume fraction changes were statistically insignificant. These metabolic changes are consistent with global WM (axonal) injury and glial activation, and suggest a possible GM host immune response.
authors: Department of Radiology, New York University School of Medicine, New York, NY, 10016, USA.
authors: William E
authors: WE
authors: Wu
authors: Assaf
authors: A
authors: Tal
authors: Ivan I
authors: II
authors: Kirov
authors: Henry
authors: H
authors: Rusinek
authors: Daniel
authors: D
authors: Charytonowicz
authors: James S
authors: JS
authors: Babb
authors: Eva-Maria
authors: EM
authors: Ratai
authors: R
authors: R
authors: Gilberto Gonzalez
authors: Oded
authors: O
authors: Gonen
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D066128:Gray Matter / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D008212:Lymphocyte Depletion; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology*; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013113:Spin Labels; D066127:White Matter / Q000378:metabolism* / Q000473:pathology
chemical_list: D013113:Spin Labels; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
keywords: HIV-1; MRS; Macaca mulatta; animal disease models; brain; simian immunodeficiency virus