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Abstract #1055

1H MRS and Tandem Mass Spectrometric Metabolite Signatures Herald HIV-1 Induced Metabolic Abnormalities in the Brains of Humanized Mice

Michael Douglas Boska1, Adrian A. Epstein2, Prasanta K. Dash2, Nathan A. Smith2, Prabagaran Narayanasamy2, Harris A. Gelbard3, Larisa Y. Poluektova2, Howard E. Gendelman2

1Radiology, University of Nebraska Medical Center, Omaha, NE, United States; 2Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE, United States; 3Neurology/Center for Neural Development and Disease, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States

Immunodeficient mice engrafted with human stem cells develop a functional human immune system. After infection with human immunodeficiency virus type one (HIV-1) these mice develop an encephalopathy reflective of human disease. The brain metabolome was elucidated at four week intervals by volume localized 1H MRS or at study end by ultraperformance liquid chromatography tandem mass spectrometry. NAA, creatine, choline brain levels were altered and changes were congruent for all methods. MRS-detected brain metabolites predicted brain pathologies in HIV-1 infected humanized mice. The studies are of translational value in predicting disease course or response to therapy in an infected human host.

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Keywords

abnormalities absolute accordance acquisition additionally aged agreement allow alterations analyses analytical animals apparent bars biochemical blood brain brains care cell cells cerebellum cerebral characterization choline chromatography chronic concentration cortex course culture dark dash dentistry development disease disorders displayed dissected done dose doses establishment ethical evolution experimental flow frozen gates general green guidelines health herald herein human humanized immunodeficiency includes individual induced infected infection infectious ingress injected injection institutes investigated irradiated laboratory lactate life light liquid load localized long loss marked mass materials mechanisms medical medicine meningitis metabolic metabolite metabolites mice minutes mirror models nervous neural neurological neurology null parallel percentage periphery persistent pharmacology population positive post preservation press primate processed progress progressive quantification quantitative radiology reconstituted reduce reduction reductions resolution sacrifice samples school signs smith spectrometric spectrometry spectroscopic spectroscopy spectrum stable stem studied submitted sustained symptoms system tandem term termed tissue uninfected useful validated validation versus viral virus visible volume weeks