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We tested the role of GPR37 in the ischemic brain of GPR37 knockout (KO) mice, exploring the idea that GPR37 might be protective against ischemic damage. In an ischemic stroke model, GPR37 KO mice exhibited increased infarction and cell death compared with wild\u2010type (WT) mice, measured by 2,3,5\u2010triphenyl\u20102H\u2010tetrazolium chloride and TUNEL staining 24 h after stroke. Moreover, more severe functional deficits were detected in GPR37 KO mice in the adhesive\u2010removal and corner tests. In the peri\u2010infarct region of GPR37 KO mice, there was significantly more apoptotic and autophagic cell death accompanied by caspase\u20103 activation and attenuated mechanistic target of rapamycin signaling. GPR37 deletion attenuated astrocyte activation and astrogliosis compared with WT stroke controls 24\u201372 h after stroke. Immunohistochemical staining showed more ionized calcium\u2010binding adapter molecule 1\u2013positive cells in the ischemic cortex of GPR37 KO mice, and RT\u2010PCR identified an enrichment of Ml\u2010type microglia or macrophage markers in the GPR37 KO ischemic cortex. Western blotting demonstrated higher levels of inflammatory factors IL\u20101\u03b2, IL\u20106, monocyte chemoattractant protein, and macrophage inflammatory protein\u20101\u03b1 in GPR37\u2010KO mice after ischemia. Thus, GPR37 plays a multifaceted role after stroke, suggesting a novel target for stroke therapy.\u2014McCrary, M. R., Jiang, M. Q., Giddens, M. M., Zhang, J. Y., Owino, S., Wei, Z. Z., Zhong, W., Gu, X., Xin, H., Hall, R. A., Wei, L., Yu, S. P. Protective effects of GPR37\n                    <jats:italic>via<\/jats:italic>\n                    regulation of inflammation and multiple cell death pathways after ischemic stroke in mice. FASEB J. 33, 10680\u201310691 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900070r","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T15:07:05Z","timestamp":1562166425000},"page":"10680-10691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Protective effects of GPR37\n                    <i>via<\/i>\n                    regulation of inflammation and multiple cell death pathways after ischemic stroke in mice"],"prefix":"10.1096","volume":"33","author":[{"given":"Myles R.","family":"McCrary","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Q.","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Giddens","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Owino","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng Z.","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohuan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy A.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan P.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Emory University School of Medicine Atlanta Georgia USA"},{"name":"Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical Center Decatur Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3058"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.202915"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12425"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20207"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2016.12.016"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.05.007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/j.1365-2826.2011.02268.x","article-title":"Diverse roles of G-protein coupled receptors in the regulation of neurohypophyseal hormone secretion","volume":"24","author":"Sladek C. 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