Microvascular Injury in Mild Traumatic Brain Injury Accelerates Alzheimer-like Pathogenesis in Mice

Published: March 29, 2021, 1:03 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.12.036392v1?rss=1 Authors: Wu, Y., Zeng, J., Pluimer, B., Dong, S., Xie, X., Guo, X., Liang, X., Feng, S., Wu, H., Yan, Y., Chen, J.-F., Maria, N. S., Ma, Q., Gomez-Pinilla, F., Zhao, Z. Abstract: Introduction: Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer's disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored. Methods: We established a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, and examined the time courses of microvascular injury, blood-brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also determined brain clearance of {beta}-amyloid, as well as amyloid pathology and cognitive functions after mTBI in the 5xFAD mouse model of AD. Results: mTBI induced microvascular injury with BBB breakdown, pericyte loss and cerebral blood flow reduction in mice, which preceded gliosis. mTBI also impaired brain amyloid clearance via the vascular pathways. More importantly, mTBI accelerated amyloid pathology and cognitive impairment in the 5xFAD mice. Discussion: Our data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD Copy rights belong to original authors. Visit the link for more info