TY  - JOUR
PY  - 2024//
TI  - Cerebral hypoperfusion exacerbates vascular dysfunction after traumatic brain injury
JO  - Experimental neurology
A1  - Whitehead, Bailey
A1  - Corbin, Deborah
A1  - Meadows, Ethan
A1  - Zhang, Ning
A1  - Hollander, John M.
A1  - Karelina, Kate
A1  - Weil, Zachary M.
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - Traumatic brain injuries are extremely common, and although most patients recover from their injuries many TBI patients suffer prolonged symptoms and remain at a higher risk for developing cardiovascular disease and neurodegeneration. Moreover, it remains challenging to identify predictors of poor long-term outcomes. Here, we tested the hypothesis that preexisting cerebrovascular impairment exacerbates metabolic and vascular dysfunction and leads to worse outcomes after TBI. Male mice underwent a mild surgical reduction in cerebral blood flow using a model of bilateral carotid artery stenosis (BCAS) wherein steel microcoils were implanted around the carotid arteries. Then mice underwent a mild-moderate TBI, or a combination of BCAS followed by TBI 30 days post coil implantation. Gene expression profiles, cerebral blood flow, metabolic function, oxidative damage, vascular health and angiogenesis were assessed. Single nuclei RNA sequencing of endothelial cells isolated from mice after TBI showed differential gene expression profiles after TBI and BCAS, that were further altered when mice underwent both challenges. TBI but not BCAS increased mitochondrial oxidative metabolism. Both BCAS and TBI decreased cerebrovascular responses to repeated whisker stimulation. BCAS induced oxidative damage and inflammation in the vasculature as well as loss of vascular density, and reduced the numbers of angiogenic tip cells. Finally, intravascular protein accumulation was increased among mice that experienced both BCAS and TBI. Overall, our findings reveal that a prior vascular impairment significantly alters the profile of vascular health and function of the cerebrovasculature, and when combined with TBI may result in worsened outcomes.<p />  <p>Language: en</p>
LA  - en
SN  - 0014-4886
UR  - http://dx.doi.org/10.1016/j.expneurol.2024.114907
ID  - ref1
ER  -