A reproducible murine model of studying HIV-associated brain damage in stroke

Abstract

Background

Emerging clinical and epidemiological data indicates that human immunodeficiency virus (HIV) is associated with an increased risk of stroke and aggravated brain damage. We aimed to develop a reproducible murine model of photothrombotic-stroke with HIV infection that mimics the clinical situation.

Method

To evaluate the impact of HIV infection on stroke, male C57BL/6 mice were infected with EcoHIV (p24 2-4 × 10⁶/mouse; i.v.) or mock control. Four weeks post-infection, a stroke was induced by the photothrombotic method (pt-MCAO). After 72 h, a catwalk test was performed for gait impairments, and mice were euthanized for stroke outcomes.

Results

EcoHIV-infection exhibited a larger infarction, brain edema, higher IgG extravasation, hemorrhagic transformation, and gait impairments following pt-MCAO vs mock control. EcoHIV-infected mice showed higher levels of IFN-y and lower levels of IL-6, indicating immune activation without affecting IL-1β and MCP-1 in plasma and brain compared to mock pt-MCAO, suggesting unaltered inflammation. EcoHIV-infection showed increased oxidative stress markers (nitrotyrosine, and 4-hydroxynonenal) and thioredoxin interacting protein expression. Further, EcoHIV-infection significantly activated the microglia and astrocyte cells.

Conclusions

This animal model would be reliable and clinically relevant to future studies investigating pathophysiological mechanisms and developing new therapeutic approaches in stroke patients with HIV conditions.