2022
DOI: 10.21203/rs.3.rs-1462737/v1
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Selective Sphingosine-1-phosphate Receptor 1 Modulator Attenuates Blood–brain Barrier Disruption Following Traumatic Brain Injury by Inhibiting Vesicular Transcytosis

Abstract: BackgroundTraumatic brain injury (TBI) provokes secondary pathological damage, such as damage to the blood–brain barrier (BBB), ischaemia and inflammation. Major facilitator superfamily domain-containing 2a (Mfsd2a) has been demonstrated to be critical in limiting the increase in BBB vesicle transcytosis following brain injury. Recent studies suggest that a novel and selective modulator of the sphingosine-1-phosphate receptor 1 (S1P1), CYM-5442, maintains the integrity of the BBB by restricting vesicle transcy… Show more

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“…Although it is a product of the same sphingomyelin as ceramide, S1P has a different physiological function. Unlike S1P2, which aggravates endothelial impairment (129), S1P1 and S1P3 safeguard ECs barrier function and promote vasodilation to improve the tissue blood supply (130, 275,276). S1P1 is expressed in cerebrovascular ECs and, upon activation, maintains responsiveness to vasodilatory stimuli, and may ensure collateral circulation to ischemic brain tissue via eNOS (130).…”
Section: S1pmentioning
confidence: 99%
“…Although it is a product of the same sphingomyelin as ceramide, S1P has a different physiological function. Unlike S1P2, which aggravates endothelial impairment (129), S1P1 and S1P3 safeguard ECs barrier function and promote vasodilation to improve the tissue blood supply (130, 275,276). S1P1 is expressed in cerebrovascular ECs and, upon activation, maintains responsiveness to vasodilatory stimuli, and may ensure collateral circulation to ischemic brain tissue via eNOS (130).…”
Section: S1pmentioning
confidence: 99%