{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:54:53Z","timestamp":1780491293024,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T00:00:00Z","timestamp":1603152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81501140"],"award-info":[{"award-number":["81501140"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502656"],"award-info":[{"award-number":["81502656"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acute ischemic stroke is one of the leading causes of death in developed countries and the most common cause of disability in adults worldwide. Despite advances in the understanding of stroke pathophysiology, therapeutic options remain limited. In this study, we explored the interaction of Shrm4 and the metabotropic gamma\u2010aminobutyric acid (GABA) receptors (GABA\n                    <jats:sub>B<\/jats:sub>\n                    ) in ischemic stroke. A transient middle cerebral artery occlusion (MCAO) model was induced by filament insertion in Shrm4+\/+ and wild\u2010type C57BL\/6J mice, followed by reperfusion for up to 7\u00a0days. Baclofen was administered was used to activate GABA\n                    <jats:sub>B<\/jats:sub>\n                    in vivo during reperfusion. Neurological deficits, motor and memory functions, and infarct volume were determined in the various mouse groups. Furthermore, we also developed an oxygen\u2010glucose deprivation (OGD) cell model in primary neurons to test Shrm4\/GABA\n                    <jats:sub>B<\/jats:sub>\n                    interactions in vitro. Shrm4 was observed to decrease infarct volume and neuronal cell loss in penumbra, and rescue neurological deficits in MCAO mice. Notably, Shrm4 also increased pole climbing speed, reduced foot faults, and increased escape latency in the Morris water maze test, while reducing neuron autophagy through an interaction with GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptors. GABA\n                    <jats:sub>B<\/jats:sub>\n                    activation using baclofen further reduced OGD\u2010induced neuron damage in culture and stroke outcomes of MCAO, relative to Shrm4 alone. Taken together, Shrm4\u2010mediated GABA\n                    <jats:sub>B<\/jats:sub>\n                    activation confers neuroprotection by reducing neuronal autophagy in acute ischemic stroke.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000458rr","type":"journal-article","created":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T12:55:31Z","timestamp":1603198531000},"page":"15837-15848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Shrm4 contributes to autophagy inhibition and neuroprotection following ischemic stroke by mediating GABA\n                    <sub>B<\/sub>\n                    receptor activation"],"prefix":"10.1096","volume":"34","author":[{"given":"Ya\u2010Jing","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Anesthesia Tianjin Medical University Cancer Institute &amp; Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The Affiliated Xiangya Hospital of Center South University Changsha P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Tianjin Medical University Cancer Institute &amp; Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Tianjin Medical University Cancer Institute &amp; Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Tianjin Medical University Cancer Hospital Airport Hospital Tianjin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Hua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Tianjin Medical University Cancer Hospital Airport Hospital Tianjin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Feng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Tianjin Medical University Cancer Hospital Airport Hospital Tianjin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Ming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Tianjin Medical University Cancer Hospital Airport Hospital Tianjin P.R. China"},{"name":"Department of Radiotherapy Tianjin Medical University Cancer Institute &amp; Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Key Laboratory of Breast Cancer Prevention and Therapy Tianjin Medical University Ministry of Education Tianjin P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1212\/WNL.0000000000002925","article-title":"Global disparities in stroke and why we should care","volume":"87","author":"Shehadah A","year":"2016","journal-title":"Neurology"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61953-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70004-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-017-2938-1"},{"key":"e_1_2_9_6_1","first-page":"CD001928","article-title":"Calcium antagonists for acute ischemic stroke","volume":"2","author":"Zhang J","year":"2019","journal-title":"Cochrane Database Syst 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