ApoA-I deficiency enhances acute inflammatory responses after experimental traumatic brain injury

Abstract

Cerebral vascular injury is a common phenomenon after traumatic brain injury (TBI), with complications including vascular inflammation, decreased cerebral blood flow, and increased vessel tortuosity. Promoting cerebrovascular health may therefore be a useful therapeutic intervention after TBI. ApoA-I, the major protein constituent of circulating high-density lipoproteins (HDL) are an attractive target due to its vasoprotective and anti-inflammatory roles in periphery vessels, but little is known on whether these benefits extend to the brain. To address this gap in knowledge, this study was designed to test the novel hypothesis that ApoA-I deficiency would worsen acute vascular and inflammatory outcomes in mice after Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) TBI. ApoA-I Knockout (ApoA-I KO) and WT mice underwent single moderate-severe TBI. Histopathological outcomes at 6hr and 2 days (2D) post-injury were assessed. ApoA-I KO mice exhibited greater Intercellular Adhesion Molecule 1 (ICAM-1), a marker for vascular permeability, in the cortex at 2D post-TBI compared to WT controls, and a subtle increase in brain pro-inflammatory cytokine levels. These results suggest the role of ApoA-I in protecting against TBI induced inflammation.