Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice.
Acta Neuropathol Commun
; 9(1): 74, 2021 04 23.
Article
em En
| MEDLINE
| ID: mdl-33892818
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Concussão Encefálica
/
Progressão da Doença
/
Microvasos
/
Doença de Alzheimer
/
Disfunção Cognitiva
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Acta Neuropathol Commun
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos