{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:14:12Z","timestamp":1753892052397,"version":"3.41.2"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Stroke, a leading cause of death and disability, lacks effective treatments. Post-stroke secondary damage worsens the brain microenvironment, further exacerbating brain injury. Microglia\u2019s role in responding to stroke-induced damage in peri-infarct regions is crucial. In this study, we explored Weisheng-tang\u2019s potential to enhance ischemic outcomes by targeting microglia.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We induced middle cerebral artery occlusion and reperfusion in mice, followed by behavioral assessments and infarct volume analyses after 48\u00a0h, and examined the changes in microglial morphology through skeleton analysis.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Weisheng-tang (300\u00a0mg\/kg) significantly reduced infarction volume and alleviated neurological and motor deficits. The number of activated microglia was markedly increased within the peri-infarct territory, which was significantly reversed by Weisheng-tang. Microglial morphology analysis revealed that microglial processes were retracted owing to ischemic damage but were restored in Weisheng-tang-treated mice. This restoration was accompanied by the expression of the purinergic P2Y12 receptor (P2Y12R), a key regulator of microglial process extension. Weisheng-tang increased neuronal Kv2.1 clusters while suppressing juxtaneuronal microglial activation. The P2Y12R inhibitor\u2014ticagrelor\u2014eliminated the tissue and functional recovery that had been observed with Weisheng-tang after ischemic damage.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Weisheng-tang improved experimental stroke outcomes by modulating microglial morphology through P2Y12R, shedding light on its neuroprotective potential in ischemic stroke.<\/jats:p>","DOI":"10.3389\/fphar.2024.1347622","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T04:54:30Z","timestamp":1725425670000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Weisheng-tang protects against ischemic brain injury by modulating microglia activation through the P2Y12 receptor"],"prefix":"10.3389","volume":"15","author":[{"given":"Min Jae","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dohee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hye","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seo-Yeon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Tae","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Ju","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hwa Kyoung","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1172\/jci17864","article-title":"P2Y12 regulates platelet adhesion\/activation, thrombus growth, and thrombus stability in injured arteries","volume":"112","author":"Andre","year":"2003","journal-title":"J. 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