Apr 13, 2020

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

BioRxiv : the Preprint Server for Biology
Y. WuZhen Zhao

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 mi...Continue Reading

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Mentioned in this Paper

T-Lymphocyte
Virus
Genome
RNA Viruses
Reconstructive Surgical Procedures
Recombination, Genetic
Nucleic Acid Sequencing
B-Lymphocytes
Clone
Genomics

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