Open AccessMild hypothermia reduces endoplasmic reticulum stress‐induced apoptosis and improves neuronal functions after severe traumatic brain injury
Author(s) -
Wang ChuanFang,
Zhao ChengCheng,
He Yi,
Li ZongYang,
Liu WenLan,
Huang XianJian,
Deng YueFei,
Li WeiPing
Publication year - 2019
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.1248
Subject(s) - hypothermia , traumatic brain injury , apoptosis , tunel assay , morris water navigation task , chop , medicine , endoplasmic reticulum , unfolded protein response , western blot , anesthesia , endocrinology , hippocampus , biology , immunohistochemistry , chemotherapy , microbiology and biotechnology , biochemistry , psychiatry , gene
Background Mild hypothermia is wildly used in clinical treatment of traumatic brain injury ( TBI ). However, the effect of mild hypothermia on endoplasmic reticulum ( ER ) stress‐induced apoptosis after severe TBI is still unknown. Methods In the present study, we used BALB /c mice to investigate the efficacy of posttraumatic mild hypothermia in reducing ER stress. Severe TBI was induced by controlled cortical impact injury. Mild hypothermia treatment was performed immediately after surgery and maintained for 4 hr. The animals were euthanized at 1 and 7 days after severe TBI . The expression levels of ER stress marker proteins were evaluated using Western blot and immunofluorescence. Cell apoptosis rate was analyzed by TUNEL staining. Neuronal functions of the mice were assessed using rotarod test and Morris water maze. Results Our results revealed that mild hypothermia significantly attenuated ER stress marker proteins, including p‐ eIF 2α/ eIF 2α, ATF 4, CHOP and IRE ‐1α, and reduced apoptosis rate in the pericontusion region at 1 and 7 days after severe TBI . Interestingly, mild hypothermia also prevented the translocation of CHOP into nucleus. In addition, posttraumatic mild hypothermia significantly improved neuronal functions after severe TBI. Conclusions Our findings illustrated that mild hypothermia could reduce ER stress‐induced apoptosis and improve neuronal functions after severe traumatic brain injury.