Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice.
Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice.
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DOI：
10.1186/s40478-021-01178-7
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发表时间：
2021-04-23
影响因子：
7.1
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Wu Y;Wu H;Zeng J;Pluimer B;Dong S;Xie X;Guo X;Ge T;Liang X;Feng S;Yan Y;Chen JF;Sta Maria N;Ma Q;Gomez-Pinilla F;Zhao Z
创伤性脑损伤（TBI）被认为是阿尔茨海默病（AD）最强大的环境危险因素。除了直接的神经元损伤和神经炎症外，血管损伤也是 TBI 后病理级联的一个标志性事件。然而，TBI 与随后的 AD 发病机制之间的血管联系仍未得到充分探索。在具有受控皮质冲击的小鼠闭头轻度 TBI (mTBI) 模型中，我们检查了野生型 C57BL/6 小鼠的微血管损伤、血脑屏障 (BBB) 功能障碍、神经胶质增生和运动功能障碍的时间过程。我们还在 AD 的 5xFAD 小鼠模型中评估了 mTBI 后的 BBB 完整性、淀粉样蛋白病理学以及认知功能。 mTBI 会导致小鼠微血管损伤，导致 BBB 破坏、周细胞丢失、基底膜改变和脑血流量减少，其中 BBB 破坏先于神经胶质增生。更重要的是，mTBI 加速了 5xFAD 小鼠的血脑屏障渗漏、淀粉样蛋白病理和认知障碍。我们的数据表明，微血管损伤在 mTBI 后 AD 的发病机制中起着关键作用。因此，恢复血管功能可能对 mTBI 患者有益，并可能降低患 AD 的风险。在线版本包含可在 10.1186/s40478-021-01178-7 获取的补充材料。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s40478-021-01178-7.
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DOI：
10.3233/jad-150088
发表时间：
2015
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Dinkins MB;Dasgupta S;Wang G;Zhu G;He Q;Kong JN;Bieberich E
通讯作者：
Bieberich E
DOI：
10.1016/j.apmr.2013.01.023
发表时间：
2013-06-01
影响因子：
4.3
作者：
Corrigan, John D.;Hammond, Flora M.
通讯作者：
Hammond, Flora M.
影响因子：
5.3
作者：
Bhowmick, Saurav;D'Mello, Veera;Abdul-Muneer, P. M.
通讯作者：
Abdul-Muneer, P. M.
影响因子：
25
作者：
Munji, Roeben Nocon;Soung, Allison Luen;Daneman, Richard
通讯作者：
Daneman, Richard
影响因子：
3.7
作者：
Nikolakopoulou AM;Zhao Z;Montagne A;Zlokovic BV
通讯作者：
Zlokovic BV