{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:09:04Z","timestamp":1790294944818,"version":"4.1.0"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Prompt post\u2013hypoxia-ischemia (HI) revascularization has been suggested to improve outcome in adults and newborn subjects. Other than hypoxia-inducible factor, sensors of metabolic demand remain largely unknown. During HI, anaerobic respiration is arrested resulting in accumulation of carbohydrate metabolic intermediates. As such succinate readily increases, exerting its biological effects via a specific receptor, G-protein\u2013coupled receptor (GPR) 91. We postulate that succinate\/GPR91 enhances post-HI vascularization and reduces infarct size in a model of newborn HI brain injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              The Rice\u2013Vannucci model of neonatal HI was used. Succinate was measured by mass spectrometry, and microvascular density was evaluated by quantification of lectin-stained cryosection. Gene expression was evaluated by real-time polymerase chain reaction. Succinate levels rapidly increased in the penumbral region of brain infarcts. GPR91 was foremost localized not only in neurons but also in astrocytes. Microvascular density increased at 96 hours after injury in wild-type animals; it was diminished in GPR91-null mice leading to an increased infarct size. Stimulation with succinate led to an increase in growth factors implicated in angiogenesis only in wild-type mice. To explain the mode of action of succinate\/GPR91, we investigated the role of prostaglandin E\n              <jats:sub>2<\/jats:sub>\n              \u2013prostaglandin E receptor 4, previously proposed in neural angiogenesis. Succinate-induced vascular endothelial growth factor expression was abrogated by a cyclooxygenase inhibitor and a selective prostaglandin E receptor 4 antagonist. This antagonist also abolished succinate-induced neovascularization.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              We uncover a dominant metabolic sensor responsible for post-HI neurovascular adaptation, notably succinate\/GPR91, acting via prostaglandin E\n              <jats:sub>2<\/jats:sub>\n              \u2013prostaglandin E receptor 4 to govern expression of major angiogenic factors. We propose that pharmacological intervention targeting GPR91 could improve post-HI brain recovery.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.113.302131","type":"journal-article","created":{"date-parts":[[2013,11,28]],"date-time":"2013-11-28T05:09:51Z","timestamp":1385615391000},"page":"285-293","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":82,"title":["G-Protein\u2013Coupled Receptor 91 and Succinate Are Key Contributors in Neonatal Postcerebral Hypoxia-Ischemia Recovery"],"prefix":"10.1161","volume":"34","author":[{"given":"David","family":"Hamel","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Research Center\u2014CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (D.H., O.R., J.C.H., T.Z., X.H., J.-C.L., G.A.M., S.C.); Departments of Pharmacology (D.H., F.D., S.C.) and Biomedical Sciences (O.R., M.N.-V.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Quebec, Canada; and Department of Pharmacology and Therapeutics (M.S., B.N., S.C.), Goodman Cancer Research and Metabolomics Core Facility (O.A.M.), McGill University, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Sanchez","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center\u2014CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (D.H., O.R., J.C.H., T.Z., X.H., J.-C.L., G.A.M., S.C.); Departments of Pharmacology (D.H., F.D., S.C.) and Biomedical Sciences (O.R., M.N.-V.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Quebec, Canada; and Department of Pharmacology and Therapeutics (M.S., B.N., S.C.), Goodman Cancer Research and Metabolomics Core Facility (O.A.M.), McGill University, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Duhamel","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center\u2014CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (D.H., O.R., J.C.H., T.Z., X.H., J.-C.L., G.A.M., S.C.); Departments of Pharmacology (D.H., F.D., S.C.) and Biomedical Sciences (O.R., M.N.-V.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Quebec, Canada; and Department of Pharmacology and Therapeutics (M.S., B.N., S.C.), Goodman Cancer Research and Metabolomics Core Facility (O.A.M.), McGill University, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Roy","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center\u2014CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (D.H., O.R., J.C.H., T.Z., X.H., J.-C.L., G.A.M., S.C.); Departments of Pharmacology (D.H., F.D., S.C.) and Biomedical Sciences (O.R., M.N.-V.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Quebec, Canada; and Department of Pharmacology and Therapeutics (M.S., B.N., S.C.), Goodman Cancer Research and Metabolomics Core Facility (O.A.M.), McGill University, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Honor\u00e9","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Research Center\u2014CHU Ste-Justine, Montr\u00e9al, Quebec, Canada (D.H., O.R., J.C.H., T.Z., X.H., J.-C.L., G.A.M., S.C.); 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