Global sphingosine-1-phosphate receptor 2 deficiency attenuates neuroinflammation and ischemic-reperfusion injury after neonatal stroke.

Abstract

Arterial ischemic stroke is common in neonates-1 per 2,300-5,000 births-and therapeutic targets remain insufficiently defined. Sphingosine-1-phosphate receptor 2 (S1PR2), a major regulator of the CNS and immune systems, is injurious in adult stroke. Here, we assessed whether S1PR2 contributes to stroke induced by 3 h transient middle cerebral artery occlusion (tMCAO) in S1PR2 heterozygous (HET), knockout (KO), and wild type (WT) postnatal day 9 pups. HET and WT of both sexes displayed functional deficits in Open Field test whereas injured KO at 24 h reperfusion performed similarly to naives. S1PR2 deficiency protected neurons, attenuated infiltration of inflammatory monocytes, and altered vessel-microglia interactions without reducing increased cytokine levels in injured regions at 72 h. Pharmacologic inhibition of S1PR2 after tMCAO by JTE-013 attenuated injury 72 h after tMCAO. Importantly, the lack of S1PR2 alleviated anxiety and brain atrophy during chronic injury. Altogether, we identify S1PR2 as a potential new target for mitigating neonatal stroke.

• Authors: Yumi Fukuzaki, Joel Faustino, Matthieu Lecuyer, Aditya Rayasam, Zinaida S Vexler
• Journal: iScience (iScience) Vol. 26 Issue 4 Pg. 106340 (Apr 21 2023) ISSN: 2589-0042 [Electronic] United States
• PMID: 37009213 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors.