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Temporal Sex Differences in Blood Brain Barrier and Vascular Recovery After Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) in males has been extensively studied but less so in females. There is a general understanding that females and males’ recover differently after TBI but this has not been extensively documented. A significant gap is how the vasculature and blood brain barrier (BBB) is altered in females after TBI. Adult C57/BL6 male and female mice underwent a moderate cortical TBI. At selected time points BBB leakage and lesion volumes were assessed by magnetic resonance imaging (MRI) at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (DPI). We also obtained classical vessel characteristics and complexity using our novel vessel painting technique at 60 DPI. We observed that females had a significant increase in vascular complexity at 60 DPI compared to the male mice. In contrast, males exhibited an increased BBB leakage and a more elevated lesion volumes over the 60 DPI time course. Our novel findings confirm that the response to a penetrating TBI in female mice is radically different than in male mice. These data provide additional evidence that treatment of TBI should be different between males and female subjects, particularly long-term treatment strategies.