MILD TRAUMATIC BRAIN INJURY INDUCES VASCULAR IMPAIRMENT AND AMYLOID CLEARANCE DEFICITS IN MICE

Abstract

TBI is considered the most robust environmental risk factor for Alzheimer's disease (AD), how exactly cerebrovascular impairment of TBI (especially mTBI) influences AD pathogenesis is still a big challenge in research field. Close-head mild brain injury mouse model was established; In vivo micro-dialysis and interstitial fluid (ISF) amyloid β (Aβ) half-life determination in TBI-affected hemisphere compared to unaffected contralateral; Immunohistochemistry and Cognitive impairment evaluation were performed after TBI. mTBI induced Blood-brain barrier dysfunction and cerebral blood flow reduction, and it also altered structural integrity of perivascular space and basement membrane, which contributed to the accelerated amyloid pathologies and cognitive impairment by impairing the brain β-amyloid (Aβ) clearance through vascular pathways. Vascular impairment plays a key role in mTBI pathogenesis and which is a potential risk for accelerating the progression of AD.