| Literature DB >> 33249091 |
Shanshan Song1, Huachen Huang2, Xiudong Guan2, Victoria Fiesler1, Mohammad Iqbal H Bhuiyan1, Ruijia Liu2, Shayan Jalali2, Md Nabiul Hasan1, Albert K Tai3, Ansuman Chattopadhyay4, Srilakshmi Chaparala4, Ming Sun5, Donna B Stolz5, Pingnian He6, Dritan Agalliu7, Dandan Sun8, Gulnaz Begum9.
Abstract
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.Entities:
Keywords: Angiogenesis; Astrocytes; Blood-Brain barrier; Na(+)/H(+)exchanger isoform-1; Wnt/β-catenin signaling
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Year: 2020 PMID： 33249091 PMCID： PMC7925353 DOI： 10.1016/j.pneurobio.2020.101963
Source DB: PubMed Journal: Prog Neurobiol ISSN： 0301-0082 Impact factor: 11.685