title: Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice.
abstract: Progressive human immunodeficiency viral (HIV) infection commonly leads to a constellation of cognitive, motor, and behavioral impairments. These are collectively termed HIV-associated neurocognitive disorders (HAND). While antiretroviral therapy (ART) reduces HAND severity, it does not affect disease prevalence. Despite decades of research, there remain no biomarkers for HAND and all potential comorbid conditions must first be excluded for a diagnosis to be made. To this end, we now report that manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) can reflect brain region-specific HIV-1-induced neuropathology in chronically virus-infected NOD/scid-IL-2Rγc(null) humanized mice. MEMRI diagnostics mirrors the abilities of Mn(2+) to enter and accumulate in affected neurons during disease. T1 relaxivity and its weighted signal intensity are proportional to Mn(2+) activities in neurons. In 16-week virus-infected humanized mice, altered MEMRI signal enhancement was easily observed in affected brain regions. These included, but were not limited to, the hippocampus, amygdala, thalamus, globus pallidus, caudoputamen, substantia nigra, and cerebellum. MEMRI signal was coordinated with levels of HIV-1 infection, neuroinflammation (astro- and micro-gliosis), and neuronal injury. MEMRI accurately demonstrates the complexities of HIV-1-associated neuropathology in rodents that reflects, in measure, the clinical manifestations of neuroAIDS as it is seen in a human host.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Aditya N
authors.initials: AN
authors.lastname: Bade
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Prasanta K
authors.initials: PK
authors.lastname: Dash
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Makarov
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198-1045, USA.
authors.forename: Balasrinivasa R
authors.initials: BR
authors.lastname: Sajja
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Larisa Y
authors.initials: LY
authors.lastname: Poluektova
authors.affiliation: Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, 68198-4375, USA.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.|Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198-1045, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Boska
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA. yutongliu@unmc.edu.|Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198-1045, USA. yutongliu@unmc.edu.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000821:virology*; D018450:Disease Progression; D015658:HIV Infections / Q000175:diagnosis*; D015497:HIV-1 / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008345:Manganese / Q000737:chemistry*; D051379:Mice; D008954:Models, Biological; D012815:Signal Processing, Computer-Assisted; D013997:Time Factors
chemical_list: D018952:Antigens, CD34; D008345:Manganese
keywords: Biomarkers; HIV-1 neuropathology; Humanized mice; Manganese-enhanced MRI (MEMRI); Neuroinflammation