{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T06:59:03Z","timestamp":1794553143698,"version":"4.9.1"},"reference-count":152,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"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>Poor outcomes in Subarachnoid Hemorrhage (SAH) are in part due to a unique form of secondary neurological injury known as Delayed Cerebral Ischemia (DCI). DCI is characterized by new neurological insults that continue to occur beyond 72 h after the onset of the hemorrhage. Historically, it was thought to be a consequence of hypoperfusion in the setting of vasospasm. However, DCI was found to occur even in the absence of radiographic evidence of vasospasm. More recent evidence indicates that catastrophic ionic disruptions known as Cortical Spreading Depolarizations (CSD) may be the culprits of DCI. CSDs occur in otherwise healthy brain tissue even without demonstrable vasospasm. Furthermore, CSDs often trigger a complex interplay of neuroinflammation, microthrombi formation, and vasoconstriction. CSDs may therefore represent measurable and modifiable prognostic factors in the prevention and treatment of DCI. Although Ketamine and Nimodipine have shown promise in the treatment and prevention of CSDs in SAH, further research is needed to determine the therapeutic potential of these as well as other agents.<\/jats:p>","DOI":"10.3390\/ijms24129883","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T03:29:48Z","timestamp":1686194988000},"page":"9883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cortical Spreading Depolarization and Delayed Cerebral Ischemia; Rethinking Secondary Neurological Injury in Subarachnoid Hemorrhage"],"prefix":"10.3390","volume":"24","author":[{"given":"Ashir","family":"Mehra","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Bischof","sequence":"additional","affiliation":[{"name":"Penn Presbyterian Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Diedrich","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Care, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7373-0851","authenticated-orcid":false,"given":"Krzysztof","family":"Laudanski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Care, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1001\/jamaneurol.2019.0006","article-title":"Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage according to Region, Time Period, Blood Pressure, and Smoking Prevalence in the Population","volume":"76","author":"Etminan","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nm.2333","article-title":"The Role of Spreading Depression, Spreading Depolarization and Spreading Ischemia in Neurological Disease","volume":"17","author":"Dreier","year":"2011","journal-title":"Nat. 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