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Abstract Details

Basal ganglia neuronal injury correlates with antioxidant & endothelial adhesion markers in HIV-infected brain
Infectious Disease
S29 - NeuroHIV: Pathophysiology and Clinical Phenotypes (3:52 PM-4:03 PM)
003

In HIV infection, blood-brain barrier damage in the basal ganglia correlates with cognitive impairment, suggesting vulnerability linked to endothelial dysfunction. We identified reduced pre-frontal cortex expression of heme oxygenase-1/HO-1 (antioxidant enzyme), as a cognitive dysfunction risk; we also identified brain HO-1 variation in SIV-infected macaques, which correlated with neuronal injury. We now hypothesize that human brain HO-1 expression varies regionally and correlates with endothelial adhesion markers and neuronal injury in HIV.

 

Define the correlations between brain heme oxygenase-1, endothelial activation, and neuronal injury in HIV infection.

Thirteen brain regions: i)cortical: frontal, temporal, occipital, anterior/posterior cingulate, motor, sensory cortices; ii)basal ganglia: caudate, globus pallidus; iii) others: frontal white matter; amygdala; cerebellum; pons were dissected (10 autopsies: 7 HIV+, 3 HIV-) from the National NeuroAIDS Tissue Consortium. Endothelial adhesion molecules (ICAM-1, VCAM-1, PECAM-1), neuronal markers (PSD95, synaptophysin), and HO-1 were quantified (Western blot, RT-qPCR). Analysis was by one-way ANOVA/Sidak’s correction, or two-way ANOVA/Tukey’s correction, and Pearson’s correlation. 

Brain HO-1 RNA varies regionally, and, in HIV+ subjects, correlates with endothelial molecules (ICAM-1, p<0.05; VCAM, p<.01; PECAM, p<.001) and post-synaptic neuronal integrity (PSD95, p<.0001; synaptophysin, ns) in cortical regions, but not basal ganglia. Additionally, within HIV+ subjects: i)HO-1 RNA is higher (p<.05), and PSD95 is lower (p<0.0001) in basal ganglia vs. cortical regions, consistent with our macaque findings; ii)endothelial adhesion molecules are higher in basal ganglia vs. cortical regions (ICAM-1 p<0.01, VCAM p<0.01, PECAM, ns); and iii)PSD95 is lower in basal ganglia, but not cortical regions, in HIV+ vs HIV- subjects (p<.01). 

Regional brain variation in the anti-oxidant response (HO-1) is linked to post-synaptic neuronal injury and increased endothelial adhesion markers. This suggests greater vulnerability of basal ganglia (vs cortical regions) to HIV-mediated injury, possibly through increased drive for transendothelial immune cell migration, which may be regionally regulated by HO-1. 

Authors/Disclosures
Analise Gruenewald
PRESENTER
No disclosure on file
Rolando Garza No disclosure on file
No disclosure on file
No disclosure on file
Dennis L. Kolson, MD, PhD (University of Pennsylvania) The institution of Dr. Kolson has received research support from NIH--R01 research grant.