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Previous studies suggest that the clinically proven NA\u20101 drug, with disruption of PSD95 in the neuronal terminals alongside the cerebral microvasculature, may inhibit pericytic contraction of microvessels by reducing endothelin\u20101 secretion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 1.5\u2010h tMCAO model using Balb\/c mice was employed. In\u00a0vivo two\u2010photon imaging and immunofluorescence staining were employed to assess the constriction effect of pericytes on capillaries. The impact of NR2B9c\/NA\u20101 administration (intravenously infused at a dose of 10\u2009\u03bcmol\/kg) on pericyte constriction was evaluated through immunofluorescent staining of brain sections. Additionally, The effect of NA\u20101 on cerebral perfusion was assessed using laser speckle blood flow monitoring, whole brain slice perfusion, and high\u2010magnification capillary imaging. Enzyme\u2010linked immunosorbent Assay (ELISA) was conducted to determine changes in quantitative ONOO<jats:sup>\u2212<\/jats:sup> and endothelin\u20101 (ET\u20101) content after tat\u2010NA\u20101 administration. Lastly, microtubule\u2010associated protein 2 (MAP2) staining and behavioral scores were used to evaluate the effects of NA\u20101 on infarct size and behavioral deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vivo two\u2010photon imaging and immunofluorescence staining revealed that pericyte constriction following ischemia and recanalization resulted in a decreased diameter of capillaries, particularly at the soma and adjacent areas. Notably, capillary obstruction was localized near pericytes. After administration of NA\u20101, the immunofluorescence staining section showed that the diameter of capillaries at pericytes' soma and in the adjacent parts increased. The ELISA results indicated a reduction in ONOO<jats:sup>\u2212<\/jats:sup> and ET\u20101 levels. Additionally, MAP2 staining revealed a decrease in infarct size, while behavioral scores showed improvements in deficits. This effect of NA\u20101 was counteracted notably when added ET\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NA\u20101 inhibits pericyte constriction following ischemia\u2013reperfusion by reducing ET\u20101 levels. It improves capillary no\u2010reflow in mice, enhances cerebral perfusion, decreases infarct size, and mitigates behavioral deficits.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70409","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T02:55:42Z","timestamp":1748228142000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of <scp>NA<\/scp>\u20101 on Pericyte\u2010Driven Vasoconstriction and Its Role in No\u2010Reflow During Cerebral Ischemia\u2013Reperfusion"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2731-3659","authenticated-orcid":false,"given":"Xinxuan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases  Beijing 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