Brain, Vol. 124, No. 5, 1033-1042,
May 2001
© 2001 Oxford University Press
Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection
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1 Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, Maryland, Departments of 2 Neurosciences and 3 Psychiatry and 4 HIV Neurobehavioral Research Center, Brain Image Analysis Laboratory, University of California San Diego, San Diego, California and Departments of 5 Psychology and 6 Psychiatry, University of Arizona, Tucson, Arizona, USA
Correspondence to:
Ronald Ellis, HIV Neurobehavioral Research Center (HNRC), University of California, San Diego, 150 West Washington Street, 2nd Floor, San Diego, CA 92103, USA E-mail: roellis@ucsd.edu
Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. In the present cross-sectional study of 94 HIV-1-infected patients, elevated CSF quinolinic acid concentrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) but not in regions relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white matter). Increased CSF quinolinic acid concentrations also correlated with higher CSF HIV-1 RNA levels. In support of the specificity of these associations, blood levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF levels of ß2-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis.
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