4.1 Article

Early glial activation precedes neurodegeneration in the cerebral cortex after SIV infection: A 3D, multivoxel proton magnetic resonance spectroscopy study

Journal

HIV MEDICINE
Volume 16, Issue 6, Pages 381-387

Publisher

WILEY
DOI: 10.1111/hiv.12222

Keywords

cerebral cortex; magnetic resonance imaging; magnetic resonance spectroscopy; neuroglia; simian immunodeficiency virus

Funding

  1. NCRR NIH HHS [S10RR019933, S10RR022976] Funding Source: Medline
  2. NIBIB NIH HHS [EB01015] Funding Source: Medline
  3. NINDS NIH HHS [NS050520, NS059331, NS040237, NS050041] Funding Source: Medline

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ObjectivesAs approximate to 40% of HIV-infected individuals experience neurocognitive decline, we investigated whether proton magnetic resonance spectroscopic imaging (H-1-MRSI) detects early metabolic abnormalities in the cerebral cortex of a simian immunodeficiency virus (SIV)-infected rhesus monkey model of neuroAIDS. MethodsThe brains of five rhesus monkeys before and 4 or 6 weeks after SIV infection (with CD8(+) T-cell depletion) were assessed with T-2-weighted quantitative magnetic resonance imaging (MRI) and 16x16x4 multivoxel H-1-MRSI (echo time/repetition time=33/1440ms). Grey matter and white matter masks were segmented from the animal MRIs and used to produce cortical masks co-registered to H-1-MRSI data to yield cortical metabolite concentrations of the glial markers myo-inositol (mI), creatine (Cr) and choline (Cho), and of the neuronal marker N-acetylaspartate (NAA). The cortex volume within the large, 28cm(3) (approximate to 35% of total monkey brain) volume of interest was also calculated for each animal pre- and post-infection. Mean metabolite concentrations and cortex volumes were compared pre- and post-infection using paired sample t-tests. ResultsThe mean (standard deviation) pre-infection concentrations of the glial markers mI, Cr and Cho were 5.8 +/- 0.9, 7.2 +/- 0.4 and 0.9 +/- 0.1mM, respectively; these concentrations increased 28% (p approximate to 0.06), 15% and 10% (both p<0.05), respectively, post-infection. The mean concentration of neuronal marker NAA remained unchanged (7.0 +/- 0.6mM pre-infection vs. 7.3 +/- 0.8mM post-infection; p approximate to 0.37). The mean cortex volume was also unchanged (8.1 +/- 1.1 cm(3) pre-infection vs. 8.3 +/- 0.5 cm(3) post-infection; p approximate to 0.76). ConclusionsThese results support the hypothesis that early cortical glial activation occurs after SIV infection prior to the onset of neurodegeneration. This suggests HIV therapeutic interventions should potentially target early glial activation in the cerebral cortex.

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