System Used:
RFLSI-ZW Laser Speckle
Contrast Imager
Authors:
Yingxi Wu 1, Jianxiong Zeng 1, Brock Pluimer 1, 2, Shirley Dong 1, Xiaochun Xie 1, Xinying Guo 1, Xinyan Liang 1, Sudi Feng 1, Haijian Wu 1, Youzhen Yan 1, Jian-Fu Chen 3, Naomi Sta Maria 1, Qingyi Ma 4, Fernando Gomez-Pinilla 5, and Zhen Zhao 1, 2
In this study, the researchers explore the connection between traumatic brain injury (TBI) and Alzheimer’s disease (AD), with a particular focus on vascular impairment. They find that mild TBI triggers microvascular injury, leading to blood-brain barrier dysfunction, reduced blood flow, and β-amyloid accumulation. Importantly, this vascular impairment accelerates the development of amyloid pathology and cognitive decline in an AD mouse model. The study suggests that addressing vascular dysfunction could offer a promising avenue for reducing AD risk in individuals who have experienced mild traumatic brain injury, shedding new light on this complex relationship and its potential therapeutic implications.
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 the brain clearance of βamyloid, 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.
