{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:09:52Z","timestamp":1789268992269,"version":"build-2803163510"},"reference-count":79,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Disorders and Stroke of the National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Multiple sclerosis is a chronic autoimmune disease in which the immune system attacks the protective sheath or myelin that covers nerve fibers, impacting the brain\u2019s ability to communicate with other areas of the body. This abnormal immune response recruits inflammatory substances, which appear as lesions on the brain and spinal cord. A stroke is characterized by a sudden impairment of neurological function resulting from the loss or restriction of blood flow due to acute damage to a localized area of the central nervous system, including the brain, retina, or spinal cord. While strokes, both ischemic and hemorrhagic, are different in terms of their pathogenesis to MS, mechanisms such as neuroinflammation and neurodegeneration are common denominators among these conditions. Recent studies highlight the involvement of the sphingosine-1-phosphate receptor in the treatment of strokes and how fingolimod, an S1P receptor modulator employed in MS treatment, may play a role in the treatment of stroke-like symptoms. This review aims to explore the potential link between stroke and MS, providing a comprehensive analysis of the existing evidence. It will also shed light on the role of S1P receptors in the pathophysiology of stroke, offering insights into their mechanistic contributions. Furthermore, the review will examine recent studies investigating the therapeutic potential of the S1P modulator, fingolimod, in acute stroke patients, highlighting its efficacy and potential clinical applications. Through this multifaceted approach, we hope to contribute to the development of a deeper understanding of these interconnected neurological conditions and their treatment strategies.<\/jats:p>","DOI":"10.3390\/brainsci15050436","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:04:50Z","timestamp":1745467490000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sphingosine-1-Phosphate Modulation in Neurological Disorders: Insights from MS and Stroke"],"prefix":"10.3390","volume":"15","author":[{"given":"Briana","family":"Maktabi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faheem","family":"Shehjar","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Senger","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Kountz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenan","family":"Maaieh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylee","family":"Hoersten","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7085-7912","authenticated-orcid":false,"given":"Jovana","family":"Duric","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-1618","authenticated-orcid":false,"given":"Zahoor A.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/S0140-6736(02)08220-X","article-title":"Multiple sclerosis","volume":"359","author":"Compston","year":"2002","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1006\/jaut.1999.0321","article-title":"Multiple sclerosis and central nervous system demyelination","volume":"13","author":"Pouly","year":"1999","journal-title":"J. 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