Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice

Aditya N. Bade, Santhi Gorantla, Prasanta K. Dash, Edward Makarov, Balasrinivasa R. Sajja, Larisa Y. Poluektova, Jiangtao Luo, Howard E. Gendelman, Michael D. Boska, Yutong Liu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 (Mn2+)-enhanced magnetic resonance imaging (MEMRI) can reflect brain region-specific HIV-1-induced neuropathology in chronically virus-infected NOD/scid-IL-2Rγcnull humanized mice. MEMRI diagnostics mirrors the abilities of Mn2+ to enter and accumulate in affected neurons during disease. T1 relaxivity and its weighted signal intensity are proportional to Mn2+ 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.

Original languageEnglish (US)
Pages (from-to)3286-3297
Number of pages12
JournalMolecular Neurobiology
Volume53
Issue number5
DOIs
StatePublished - Jul 1 2016

Keywords

  • Biomarkers
  • HIV-1 neuropathology
  • Humanized mice
  • Manganese-enhanced MRI (MEMRI)
  • Neuroinflammation

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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