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However, the effect of mild hypothermia on endoplasmic reticulum (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) stress\u2010induced apoptosis after severe <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, we used <jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c mice to investigate the efficacy of posttraumatic mild hypothermia in reducing <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress. Severe <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> was induced by controlled cortical impact injury. Mild hypothermia treatment was performed immediately after surgery and maintained for 4\u00a0hr. The animals were euthanized at 1 and 7\u00a0days after severe <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content>. The expression levels of <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress marker proteins were evaluated using Western blot and immunofluorescence. Cell apoptosis rate was analyzed by <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> staining. Neuronal functions of the mice were assessed using rotarod test and Morris water maze.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results revealed that mild hypothermia significantly attenuated <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress marker proteins, including p\u2010<jats:styled-content style=\"fixed-case\">eIF<\/jats:styled-content>2\u03b1\/<jats:styled-content style=\"fixed-case\">eIF<\/jats:styled-content>2\u03b1, <jats:styled-content style=\"fixed-case\">ATF<\/jats:styled-content>4, <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IRE<\/jats:styled-content>\u20101\u03b1, and reduced apoptosis rate in the pericontusion region at 1 and 7\u00a0days after severe <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content>. Interestingly, mild hypothermia also prevented the translocation of <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> into nucleus. In addition, posttraumatic mild hypothermia significantly improved neuronal functions after severe TBI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings illustrated that mild hypothermia could reduce <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress\u2010induced apoptosis and improve neuronal functions after severe traumatic brain injury.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1248","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T02:47:31Z","timestamp":1551754051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Mild hypothermia reduces endoplasmic reticulum stress\u2010induced apoptosis and improves neuronal functions after severe traumatic brain injury"],"prefix":"10.1002","volume":"9","author":[{"given":"Chuan\u2010Fang","family":"Wang","sequence":"first","affiliation":[{"name":"Zhongshan School of Medicine Sun Yat\u2010sen University Guangzhou Guangdong China"},{"name":"Brain Center Shenzhen Key Laboratory of Neurosurgery The First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Cheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[{"name":"Brain Center Shenzhen Key Laboratory of Neurosurgery The First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zong\u2010Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Brain Center Shenzhen Key Laboratory of Neurosurgery The 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