| Publication Abstract Display | | Type: Published Abstract | | Title: Elevated CSF quinolinate levels are specifically associated with volume loss in the striatum and limbic cortex on brain MRI in subjects with HIV infection. | | Authors: Ellis RJ, Ryan L, Heyes M, Jernigan TL, McCutchan JA, Archibald S, Heaton RK, Grant I, and the HNRC Group | | Year: 1998 | | Publication: Journal of NeuroVirology | | Volume: 4 Issue: Pages: 348 | | Abstract:Background: Quinolinic acid (QUIN), a neuronal excitotoxin secreted by activated CNS mononuclear cells and acting through glutamatergic (NMDA) receptors, may contribute to neurodegeneration in HIV-associated cognitive disorders, including dementia.
Methods: Because animal models have suggested that the limbic cortex and the striatum (caudate, globus pallidus) are particularly vulnerable to quinolinate-mediated neurotoxicity, we determined the correlation between quinolinic acid concentrations in cerebrospinal fluid (CSF) and regional cerebral volumes in the striatum and limbic cortex on quantitated magnetic resonance (MR) scans. To evaluate the specificity of these associations, we also studied MR volumes of the thalamus, nonlimbic cortex, and white matter, as well as beta-2 microglobulin (B2M) levels in CSF.
Results: In 78 HIV-infected patients, elevated CSF QUIN levels were significantly correlated with volume loss in the striatum (r = -.28; p<.01) and limbic cortex (r = -.33; p<.01), but not in the other brain areas (rs <.16). The correlations were independent of disease stage, CSF concentrations of beta-2-microglobulin, and serum QUIN level. Treatment with zidovudine, which is known to diminish CSF QUIN levels, attenuated the strength of the correlation between CSF QUIN and regional brain volumes. In zidovudine-naive patients, elevated CSF QUIN levels were associated with poorer performance on tests of learning and memory.
Conclusions: These results support the hypothesis that elevated quinolinic acid concentrations in the central nervous system act. |
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