{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:43:30Z","timestamp":1792597410784,"version":"4.5.0"},"reference-count":79,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nimodipine is the current gold standard in the treatment of subarachnoid hemorrhage, as it is the only known calcium channel blocker that has been proven to improve neurological outcomes. In addition, nimodipine exhibits neuroprotective properties in vitro under various stress conditions. Furthermore, clinical studies have demonstrated a neuroprotective effect of nimodipine after vestibular schwannoma surgery. However, the molecular mode of action of nimodipine pre-treatment has not been well investigated. In the present study, using real-time cell death assays, we demonstrated that nimodipine not only reduces cell death induced by osmotic and oxidative stress but also protects cells directly at the time of stress induction in Schwann cells. Nimodipine counteracts stress-induced calcium overload and the overexpression of the Cav1.2 calcium channel. In addition, we found nimodipine-dependent upregulation of sarcoplasmic\/endoplasmic reticulum calcium ATPase 3 (SERCA3) and LIM domain only 4 (LMO4) protein. Analysis of anti-apoptotic cell signaling showed an inhibition of the pro-apoptotic protein glycogen synthase kinase 3 beta (GSK3\u03b2). Nimodipine-treated Schwann cells exhibited higher levels of phosphorylated GSK3\u03b2 at serine residue 9 during osmotic and oxidative stress. In conclusion, nimodipine prevents cell death by protecting cells from calcium overload by fine-tuning intracellular calcium signaling and gene expression.<\/jats:p>","DOI":"10.3390\/ijms26020864","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:53:32Z","timestamp":1737442412000},"page":"864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Protective Effect of Nimodipine in Schwann Cells Is Related to the Upregulation of LMO4 and SERCA3 Accompanied by the Fine-Tuning of Intracellular Calcium Levels"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4581-5185","authenticated-orcid":false,"given":"Sandra","family":"Leisz","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Fritzsche","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9624-1487","authenticated-orcid":false,"given":"Christian","family":"Scheller","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nature19102","article-title":"Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs","volume":"537","author":"Tang","year":"2016","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1161\/01.RES.55.3.336","article-title":"Voltage-dependent block of calcium channel current in the calf cardiac Purkinje fiber by dihydropyridine calcium channel antagonists","volume":"55","author":"Sanguinetti","year":"1984","journal-title":"Circ. 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