{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:13:04Z","timestamp":1753891984353,"version":"3.41.2"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022299","name":"School of Medicine, Shahid Beheshti University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022299","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The abrupt hyperglycemic reperfusion following thrombectomy has been shown to harm the efficacy of the intervention in stroke patients with large vessel occlusion. Studies of ours and others have shown thioredoxin-interacting protein (TXNIP) is critically involved in hyperglycemic stroke injury. We recently found verapamil ameliorates cerebrovascular toxicity of tissue plasminogen activators in hyperglycemic stroke. The present study aims to answer if verapamil exerts direct neuroprotective effects and alleviates glucose toxicity following thrombectomy in a preclinical model of hyperglycemic stroke. Primary cortical neural (PCN) cultures were exposed to hyperglycemic reperfusion following oxygen-glucose deprivation (OGD), with or without verapamil treatment. In a mouse model of intraluminal stroke, animals were subjected to 4\u00a0h middle cerebral artery occlusion (MCAO) and intravenous glucose infusion. Glucose infusion lasted one more hour at reperfusion, along with intra-arterial (i.a.) verapamil infusion. Animals were subjected to sensorimotor function tests and histological analysis of microglial phenotype at 72\u00a0h post-stroke. According to our findings, glucose concentrations (2.5\u201320\u00a0mM) directly correlated with TXNIP expression in OGD-exposed PCN cultures. Verapamil (100\u00a0nM) effectively improved PCN cell neurite growth and reduced TXNIP expression as well as interaction with NOD-like receptor pyrin domain-containing-3 (NLRP3) inflammasome, as determined by immunoblotting and immunoprecipitation. In our mouse model of extended hyperglycemic MCAO, i.a. verapamil (0.5\u00a0mg\/kg) could attenuate neurological deficits induced by hyperglycemic stroke. This was associated with reduced microglial pro-inflammatory transition. This finding encourages pertinent studies in hyperglycemic patients undergoing thrombectomy where the robust reperfusion may exacerbate glucose toxicity.<\/jats:p>","DOI":"10.3389\/fphar.2023.1161999","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T11:26:29Z","timestamp":1681385189000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Intra-arterial verapamil improves functional outcomes of thrombectomy in a preclinical model of extended hyperglycemic stroke"],"prefix":"10.3389","volume":"14","author":[{"given":"Sanaz","family":"Nasoohi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parsa","family":"Alehossein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masoumeh","family":"Jorjani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candice M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tauheed","family":"Ishrat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s12975-020-00844-7","article-title":"Deferoxamine treatment prevents post-stroke vasoregression and neurovascular unit remodeling leading to improved functional outcomes in type 2 male diabetic rats: Role of endothelial ferroptosis","volume":"12","author":"Abdul","year":"2021","journal-title":"Transl. stroke Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3108","DOI":"10.1096\/fj.201700856RRR","article-title":"Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo","volume":"32","author":"Bedarida","year":"2018","journal-title":"FASEB J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1161\/strokeaha.111.637769","article-title":"Insulin for glycemic control in acute ischemic stroke","volume":"43","author":"Bellolio","year":"2012","journal-title":"Stroke"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1097\/01.WCB.0000087090.01171.E7","article-title":"Translocation of apoptosis-inducing factor in vulnerable neurons after transient cerebral ischemia and in neuronal cultures after oxygen-glucose deprivation","volume":"23","author":"Cao","year":"2003","journal-title":"J. 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