{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:58:22Z","timestamp":1792497502180,"version":"4.5.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              The mitochondrial unfolded protein response (UPR\n              <jats:sup>mt<\/jats:sup>\n              ) is an evolutionarily conserved mitochondrial response that is critical for maintaining mitochondrial and energetic homeostasis under cellular stress after tissue injury and disease. Here, we ask whether UPR\n              <jats:sup>mt<\/jats:sup>\n              may be a potential therapeutic target for ischemic stroke.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We performed the middle cerebral artery occlusion and oxygen-glucose deprivation models to mimic ischemic stroke in vivo and in vitro, respectively. Oligomycin and meclizine were used to trigger the UPR\n              <jats:sup>mt<\/jats:sup>\n              . We used 2,3,5-triphenyltetrazolium chloride staining, behavioral tests, and Nissl staining to evaluate cerebral injury in vivo. The Cell Counting Kit-8 assay and the Calcein AM Assay Kit were conducted to test cerebral injury in vitro.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Inducing UPR\n              <jats:sup>mt<\/jats:sup>\n              with oligomycin protected neuronal cultures against oxygen-glucose deprivation. UPR\n              <jats:sup>mt<\/jats:sup>\n              could also be triggered with meclizine, and this Food and Drug Administration-approved drug also protected neurons against oxygen-glucose deprivation. Blocking UPR\n              <jats:sup>mt<\/jats:sup>\n              with siRNA against activating transcription factor 5 eliminated the neuroprotective effects of meclizine. In a mouse model of focal cerebral ischemia, pretreatment with meclizine was able to induce UPR\n              <jats:sup>mt<\/jats:sup>\n              in vivo, which reduced infarction and improved neurological outcomes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              These findings suggest that the UPR\n              <jats:sup>mt<\/jats:sup>\n              is important in maintaining the survival of neurons facing ischemic\/hypoxic stress. The UPR\n              <jats:sup>mt<\/jats:sup>\n              mechanism may provide a new therapeutic avenue for ischemic stroke.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.123.045550","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T19:01:05Z","timestamp":1719255665000},"page":"1904-1913","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["ATF5-Mediated Mitochondrial Unfolded Protein Response (UPR\n            <sup>mt<\/sup>\n            ) Protects Neurons Against Oxygen-Glucose Deprivation and Cerebral Ischemia"],"prefix":"10.1161","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6803-9778","authenticated-orcid":true,"given":"Hong","family":"An","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, China (H.A.)."},{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."},{"name":"Cerebrovascular and Neuroscience Research Institute, Xuanwu Hospital, Capital Medical University, Beijing, China (H.A., J.S., D.W., X.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, China (B.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-2413","authenticated-orcid":true,"given":"Kazuhide","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1679-4744","authenticated-orcid":true,"given":"Violeta","family":"Dur\u00e1n Laforet","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."},{"name":"Unidad de Investigaci\u00f3n Neurovascular, Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid (UCM), Instituto de Investigaci\u00f3n Hospital 12 de Octubre, Spain (V.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4714-930X","authenticated-orcid":true,"given":"Ji-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."},{"name":"Department of Emergency and Critical Care Medicine, Fukuoka University Hospital, Japan (Y.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-0923","authenticated-orcid":true,"given":"Emiri T.","family":"Mandeville","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-0359","authenticated-orcid":true,"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Neuroscience Research Center, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA (N.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhen","family":"Guo","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-9671","authenticated-orcid":true,"given":"Jingfei","family":"Shi","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."},{"name":"Cerebrovascular and Neuroscience Research Institute, Xuanwu Hospital, Capital Medical University, Beijing, China (H.A., J.S., D.W., X.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2717-7362","authenticated-orcid":true,"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."},{"name":"Cerebrovascular and Neuroscience Research Institute, Xuanwu Hospital, Capital Medical University, Beijing, China (H.A., J.S., D.W., X.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlu","family":"Li","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (H.A., K.H., V.D.L., J.-H.P., Y.N., E.T.M., S.G., Z.Y., J.S., D.W., W.L., E.H.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9327-2915","authenticated-orcid":true,"given":"Eng H.","family":"Lo","sequence":"additional","affiliation":[{"name":"Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts 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