Selective Knockout of Astrocytic Na+/H+ Exchanger Isoform 1 is Neuroprotective in Ischemic Stroke Injury

• DOI: 10.1096/fasebj.30.1_supplement.1224.21
• Publication Date: 2023-11-26T16:34:18Z
• Authors: Gulnaz Begum; Shaoxia Wang; Hanshu Zhao; Mohammad Iqbal Ho...; Rachel Nepomuceno; Qing Ye; Donna Beer Stolz; Ming Sun; Yinhuai Chen; Gary E Shull; Sun Dandan
• Keywords: Astrogliosis; Aquaporin 4

We previously reported that Na + /H exchanger isoform 1 (NHE1) plays a role in the dysregulation of ionic homeostasis astrocytes under ischemic conditions. In this study, we created an Nhe1 flox/flox mouse line ( f/f ) with exon 5 flanked two loxP sites order to selectively ablate NHE1 when crossed cell‐type specific GFAPCreER T2 Cre‐recombinase line. Gfap CreER/+ ;NHE1 mice at P60–90 were treated either tamoxifen (Tam, 75mg/kg/day, i.p.) or corn oil for days induce Cre recombination. 30 post injection, underwent transient middle cerebral artery occlusion (tMCAO) stroke. With ultrastructural and immunocytochemical analyses 2 post‐tMCAO, detected perivascular reactive astrocyte formation, extensive edema, swollen vacuolated endothelial cells damaged tight junctions oil, which was accompanied AQP4 laminin accumulation. contrast, reduced protein expression less accumulation microvessels Tam‐treated mice. Selective knockout GFAP also prevented decreased S100β release, microvessel damage BBB leakage after The ;Nhe1 Tam exhibited smaller infarct pronounced neurological function deficits. Taken together, is first study report astrocytic important astrocyte‐mediated brain damage. Support Funding Information NIH R01 NS048216 (D.S)