{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:30:17Z","timestamp":1790634617754,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T00:00:00Z","timestamp":1709424000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071385"],"award-info":[{"award-number":["82071385"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701291"],"award-info":[{"award-number":["81701291"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Non\u2010invasive transcranial direct\u2010current stimulation (tDCS) is a safe ischaemic stroke therapy. Cathodal bilateral tDCS (BtDCS) is a modified tDCS approach established by us recently. Because selenium (Se) plays a crucial role in cerebral ischaemic injury, we investigated whether cathodal BtDCS conferred neuroprotection via regulating Se\u2010dependent signalling in rat cerebral ischaemia\u2013reperfusion (I\/R) injury. We first showed that the levels of Se and its transport protein selenoprotein P (SEPP1) were reduced in the rat cortical penumbra following I\/R, whereas cathodal BtDCS prevented the reduction of Se and SEPP1. Interestingly, direct\u2010current stimulation (DCS) increased SEPP1 level in cultured astrocytes subjected to oxygen\u2010glucose deprivation reoxygenation (OGD\/R) but had no effect on SEPP1 level in OGD\/R\u2010insulted neurons, indicating that DCS may increase Se in ischaemic neurons by enhancing the synthesis and secretion of SEPP1 in astrocytes. We then revealed that DCS reduced the number of injured mitochondria in OGD\/R\u2010insulted neurons cocultured with astrocytes. DCS and BtDCS prevented the reduction of the mitochondrial quality\u2010control signalling, vesicle\u2010associated membrane protein 2 (VAMP2) and syntaxin\u20104 (STX4), in OGD\/R\u2010insulted neurons cocultured with astrocytes and the ischaemic brain respectively. Under the same experimental conditions, downregulation of SEPP1 blocked DCS\u2010 and BtDCS\u2010induced upregulation of VAMP2 and STX4. Finally, we demonstrated that cathodal BtDCS increased Se to reduce infract volume following I\/R. Together, the present study uncovered a molecular mechanism by which cathodal BtDCS confers neuroprotection through increasing SEPP1 in astrocytes and subsequent upregulation of SEPP1\/VAMP2\/STX4 signalling in ischaemic neurons after rat cerebral I\/R injury.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15968-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Cathodal bilateral transcranial direct\u2010current stimulation (BtDCS) prevents the reduction of selenium (Se) and selenoprotein P in the ischaemic penumbra.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Se plays a crucial role in cerebral ischaemia injury.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Direct\u2010current stimulation reduces mitochondria injury and blocks the reduction of vesicle\u2010associated membrane protein 2 (VAMP2) and syntaxin\u20104 (STX4) in oxygen\u2010glucose deprivation reoxygenation\u2010insulted neurons following coculturing with astrocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cathodal BtDCS regulates Se\/VAMP2\/STX4 signalling to confer neuroprotection after ischaemia.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285806","type":"journal-article","created":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T18:05:25Z","timestamp":1709489125000},"page":"1175-1197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cathodal bilateral transcranial direct\u2010current stimulation regulates selenium to confer neuroprotection after rat cerebral ischaemia\u2013reperfusion injury"],"prefix":"10.1113","volume":"602","author":[{"given":"Hui","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Neuroregeneration &amp; 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