Elevated peripheral benzodiazepine receptor expression in simian immunodeficiency virus encephalitis

Joseph L. Mankowski, Suzanne E. Queen, Patrick J. Tarwater, Robert J. Adams, Tomas R. Guilarte

Research output: Contribution to journalReview article

Abstract

Measurement of central nervous system (CNS) expression of the peripheral benzodiazepine receptor (PBR), a microglia and macrophage activation marker, by positron emission tomography (PET) would aid clinical management of human immunodeficiency virus (HIV)-infected patients. To evaluate the utility of examining PBR expression in the CNS as a cellular activation marker in HIV CNS disease, PBR levels were measured in frontal cortex of simian immunodeficiency virus (SIV)-infected macaques with encephalitis and uninfected animals via PK11195 ligand autoradiography. [3H]-(R)-PK11195 binding to both grey matter (P=.017) and white matter (P=.038) was significantly higher in animals with SIV encephalitis (n=10) versus control animals (n=3). When PK11195 binding was compared with other microglial/macrophage activation markers (obtained via quantitative image analysis), a strong, significant association was found for both HAM56 (P=.004) and KP-1 (anti-CD68; P=.006) immunostaining in white matter. In contrast, grey matter PK11195 binding did not correlate with HAM56 (P=.46), KP-1 (P=.06), or glial fibrillary acidic protein (GFAP) immunostaining for astrocytic activation (P=.09). The regional nature of these increases in activation within the brain illustrates the crucial need to focus functional neuroimaging analyses of HIV-infected individuals on subcortical white matter to assess activation of microglia and macrophages.

Original languageEnglish (US)
Pages (from-to)94-100
Number of pages7
JournalJournal of neurovirology
Volume9
Issue number1
DOIs
StatePublished - Feb 2003

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Keywords

  • Microglia
  • Peripheral benzodiazepine receptor
  • SIV

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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