Mild Traumatic Brain Injury Induces Time- and Sex-Dependent Cerebrovascular Dysfunction and Stroke Vulnerability

Mild traumatic brain injury (mTBI) produces subtle cerebrovascular impairments that persist over time and promote increased ischemic stroke vulnerability. We recently established a role for vascular impairments in exacerbating stroke outcomes 1 week after TBI, but there is a lack of research regarding long-term impacts of mTBI-induced vascular dysfunction, as well as a significant need to understand how mTBI promotes stroke vulnerability in both males and females. Here, we present data using a mild closed head TBI model and an experimental stroke occurring either 7 or 28 days later in both male and female mice. We report that mTBI induces larger stroke volumes 7 days after injury, however, this increased vulnerability to stroke persists out to 28 days in female but not male mice. Importantly, mTBI-induced changes in blood-brain barrier permeability, intravascular coagulation, angiogenic factors, total vascular area, and glial expression were differentially altered across time and by sex. Taken together, these data suggest that mTBI can result in persistent cerebrovascular dysfunction and increased susceptibility to worsened ischemic outcomes, although these dysfunctions occur differently in male and female mice.