{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:42:42Z","timestamp":1792179762721,"version":"4.4.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose:<\/jats:title>\n            <jats:p>Brain acidosis is prevalent in stroke and other neurological diseases. Acidosis can have paradoxical injurious and protective effects. The purpose of this study is to determine whether a proton receptor exists in neurons to counteract acidosis-induced injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We analyzed the expression of proton-sensitive GPCRs (G protein-coupled receptors) in the brain, examined acidosis-induced signaling in vitro, and studied neuronal injury using in vitro and in vivo mouse models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>GPR68, a proton-sensitive GPCR, was present in both mouse and human brain, and elicited neuroprotection in acidotic and ischemic conditions. GPR68 exhibited wide expression in brain neurons and mediated acidosis-induced PKC (protein kinase C) activation. PKC inhibition exacerbated pH 6-induced neuronal injury in a GPR68-dependent manner. Consistent with its neuroprotective function, GPR68 overexpression alleviated middle cerebral artery occlusion\u2013induced brain injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>These data expand our knowledge on neuronal acid signaling to include a neuroprotective metabotropic dimension and offer GPR68 as a novel therapeutic target to alleviate neuronal injuries in ischemia and multiple other neurological diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.120.031479","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T09:00:24Z","timestamp":1602838824000},"page":"3690-3700","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia"],"prefix":"10.1161","volume":"51","author":[{"given":"Tao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology (T.W., G.Z., M.H., Yuanyuan Xu, X.-m.Z.), University of South Alabama College of Medicine, Mobile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guokun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology (T.W., G.Z., M.H., Yuanyuan Xu, X.-m.Z.), University of South Alabama College of Medicine, Mobile."},{"name":"Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, China (G.Z., Y.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mindi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology (T.W., G.Z., M.H., Yuanyuan Xu, X.-m.Z.), University of South Alabama College of Medicine, Mobile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology (T.W., G.Z., M.H., Yuanyuan Xu, X.-m.Z.), University of South Alabama College of Medicine, Mobile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.G.","family":"Rusyniak","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery (W.G.R.), University of South Alabama College of Medicine, Mobile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-7996","authenticated-orcid":true,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis (Yan Xu)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Ji","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, China (G.Z., Y.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger P.","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Morehouse School of Medicine, Atlanta, GA (R.P.S., Z.-G.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Gang","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Morehouse School of Medicine, Atlanta, GA (R.P.S., Z.-G.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-2731","authenticated-orcid":true,"given":"Xiang-ming","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology (T.W., G.Z., M.H., Yuanyuan Xu, X.-m.Z.), University of South Alabama College of Medicine, Mobile."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_6_2_2","first-page":"23","article-title":"Acidosis-related brain damage.","volume":"96","author":"Siesj\u00f6 BK","year":"1993","unstructured":"Siesj\u00f6, BK, Katsura, K, Mellerg\u00e5rd, P, Ekholm, A, Lundgren, J, Smith, ML. 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