Abstract Details

Title Regional Brain Injury in the SIV Macaque Model of HIV is Linked to the Host Antioxidant Response

Topic Infectious Disease

Presentation(s) S29 - NeuroHIV: Pathophysiology and Clinical Phenotypes (3:30 PM-3:41 PM)

Poster/Presentation
Number 001

Background Brain dysfunction in HIV infection can evolve despite suppression of virus replication. Brainstem regions appear to be more vulnerable to injury, for unclear reasons. In the SIV macaque model of HIV neuropathogenesis, we previously identified regional brain differences in expression of anti-oxidant responses (heme oxygenase-1/HO-1). We hypothesize that such differences correlate with regional brain injury.

Objective Define evolving brain injury in simian immunodeficiency virus (SIV)-infected rhesus macaques and its correlation with the host antioxidant response.

Design/Methods Eighteen rhesus macaques infected with SIV were sacrificed 5, 10, 13, 20, 41, and 90 days post-infection (dpi). Nine brain regions (midbrain, parietal, basal ganglia, medulla, pons, frontal, pre-frontal, deep frontal, and cerebellum) were analyzed by western blot for neuronal markers (PSD95, SYN1, synaptophysin, and tyrosine hydroxylase (TH)), and anti-oxidant response enzymes (HO-1, GPX1). Statistical analyses were by ANOVA and multivariate linear regression.

Results Acute SIV replication level (13-20dpi) correlated with neuronal injury (decreased PSD95, synaptophysin, p<.01) and neuronal functional responses (increased SYN1, p<.05) in most brain regions, and dopaminergic responses (decreased TH, p<.05) in basal ganglia. Chronic infection (40-90dpi), showed sustained, but not progressive, neuronal injury from day 20 to day 90 (no changes in PSD95, synaptophysin), and no changes in dopaminergic responses (TH). However, cortical regions, but not brainstem regions, did show significant increases in PSD95 from day 13 to day 90pi, which suggests possible spontaneous regional brain recovery from the acute SIV injury. Brainstem regions expressed lower antioxidant responses (HO-1, GPX1; p<.001), and HO-1 expression correlated with PSD95 and synaptophysin (p<.001).

Conclusions Brain neuronal injury occurs in acute SIV infection and is sustained through chronic infection, with evidence for spontaneous recovery in cortical, but not brainstem regions. Our results support the hypothesis that lower brainstem antioxidant capacity accounts for brainstem vulnerability to, and less recovery from, SIV/HIV injury.

Authors/Disclosures
PRESENTER	No disclosure on file
Brandon Bastien	No disclosure on file
Rolando Garza	No disclosure on file
Analise Gruenewald	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.

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