Wnt信号通路
下调和上调
细胞生物学
血脑屏障
脑血流
缺血
脑缺血
冲程(发动机)
化学
神经科学
药理学
星形胶质细胞
生物
医学
信号转导
麻醉
内科学
中枢神经系统
基因
生物化学
工程类
机械工程
作者
Shanshan Song,Huachen Huang,Xiudong Guan,Victoria M. Fiesler,Mohammad Iqbal H. Bhuiyan,Ruijia Liu,Shayan Jalali,Md Nabiul Hasan,Albert Tai,Ansuman Chattopadhyay,Srilakshmi Chaparala,Ming Sun,Donna B. Stolz,Pingnian He,Dritan Agalliu,Dandan Sun,Gulnaz Begum
标识
DOI:10.1016/j.pneurobio.2020.101963
摘要
The role of astrocytes in dysregulation of blood-brain barrier (BBB) function following ischemic stroke is not well understood. Here, we investigate the effects of restoring the repair properties of astrocytes on the BBB after ischemic stroke. Mice deficient for NHE1, a pH-sensitive Na+/H+ exchanger 1, in astrocytes have reduced BBB permeability after ischemic stroke, increased angiogenesis and cerebral blood flow perfusion, in contrast to wild-type mice. Bulk RNA-sequencing transcriptome analysis of purified astrocytes revealed that ∼177 genes were differentially upregulated in mutant astrocytes, with Wnt7a mRNA among the top genes. Using a Wnt reporter line, we confirmed that the pathway was upregulated in cerebral vessels of mutant mice after ischemic stroke. However, administration of the Wnt/β-catenin inhibitor, XAV-939, blocked the reparative effects of Nhe1-deficient astrocytes. Thus, astrocytes lacking pH-sensitive NHE1 protein are transformed from injurious to "protective" by inducing Wnt production to promote BBB repair after ischemic stroke.
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