Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice

Authors

Yingxi Wu, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Haijian Wu, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Jianxiong Zeng, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Brock Pluimer, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Shirley Dong, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Xiaochun Xie, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Xinying Guo, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Tenghuan Ge, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Xinyan Liang, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Sudi Feng, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Youzhen Yan, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Jian-Fu Chen, Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.
Naomi Sta Maria, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Qingyi Ma, Lawrence D. Longo, MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, 92350, USA.Follow
Fernando Gomez-Pinilla, Brain Injury Research Center, Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Zhen Zhao, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.Follow

Document Type

Article

Publication Date

4-23-2021

Publication Title

Acta neuropathologica communications

E-ISSN

2051-5960

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: In a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, we 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 evaluated the BBB integrity, amyloid pathology as well as cognitive functions after mTBI in the 5xFAD mouse model of AD. RESULTS: mTBI induced microvascular injury with BBB breakdown, pericyte loss, basement membrane alteration and cerebral blood flow reduction in mice, in which BBB breakdown preceded gliosis. More importantly, mTBI accelerated BBB leakage, 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.

Volume

9

Issue

1

First Page

74

DOI

10.1186/s40478-021-01178-7

PubMed ID

33892818

Recommended Citation

Wu, Yingxi; Wu, Haijian; Zeng, Jianxiong; Pluimer, Brock; Dong, Shirley; Xie, Xiaochun; Guo, Xinying; Ge, Tenghuan; Liang, Xinyan; Feng, Sudi; Yan, Youzhen; Chen, Jian-Fu; Sta Maria, Naomi; Ma, Qingyi; Gomez-Pinilla, Fernando; and Zhao, Zhen, "Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice" (2021). Loma Linda University Faculty Publications. 324.
https://scholarsrepository.llu.edu/fac_pubs/324