Coregistration of quantitative proton magnetic resonance spectroscopic imaging with neuropathological and neurophysiological analyses defines the extent of neuronal impairments in murine human immunodeficiency virus type-1 encephalitis

Jay A. Nelson, H. Dou, B. Ellison, M. Uberti, H. Xiong, E. Anderson, M. Mellon, H. A. Gelbard, M. Boska, H. E. Gendelman

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Relatively few immune-activated and virus-infected mononuclear phagocytes (MP; perivascular macrophages and microglia) may affect widespread neuronal dysfunction during human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD). Indeed, histopathological evidence of neuronal dropout often belies the extent of cognitive impairment. To define relationships between neuronal function and histopathology, proton magnetic resonance spectroscopic imaging (1H MRSI) and hippocampal long-term potentiation (LTP) were compared with neuronal and glial immunohistology in a murine model of HIV-1 encephalitis (HIVE). HIV-1ADA-infected human monocyte-derived macrophages (MDM) were stereotactically injected into the subcortex of severe combined immunodeficient (SCID) mice. Sham-operated and unmanipulated mice served as controls. Seven days after cell injection, brain histological analyses revealed a focal giant cell encephalitis, with reactive astrocytes, microgliosis, and neuronal dropout. Strikingly, significant reductions in N-acetyl aspartate concentration ([NAA]) and LTP levels in HIVE mice were in both injected and contralateral hemispheres and in brain subregions, including the hippocampus, where neuropathology was limited or absent. The data support the importance of 1H MRSI as a tool for assessing neuronal function for HAD. The data also demonstrate that a highly focal encephalitis can produce global deficits for neuronal function and metabolism.

Original languageEnglish (US)
Pages (from-to)562-575
Number of pages14
JournalJournal of Neuroscience Research
Volume80
Issue number4
DOIs
StatePublished - May 15 2005

Keywords

  • HIV-1-associated dementia
  • Long-term potentiation
  • Magnetic resonance spectroscopic imaging
  • Monocyte-derived macrophages
  • Viral encephalitis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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