Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
Brain Center, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.
Brain Behav. 2019 Apr;9(4):e01248. doi: 10.1002/brb3.1248. Epub 2019 Mar 4.
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.
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.
Our results revealed that mild hypothermia significantly attenuated ER stress marker proteins, including p-eIF2α/eIF2α, ATF4, 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.
Our findings illustrated that mild hypothermia could reduce ER stress-induced apoptosis and improve neuronal functions after severe traumatic brain injury.
轻度低温广泛应用于创伤性脑损伤（TBI）的临床治疗。然而，轻度低温对严重 TBI 后内质网（ER）应激诱导的细胞凋亡的影响尚不清楚。
在本研究中，我们使用 BALB/c 小鼠来研究创伤后轻度低温对减轻 ER 应激的疗效。采用皮质撞击伤诱导严重 TBI。手术后立即进行轻度低温治疗，并持续 4 小时。严重 TBI 后 1 天和 7 天处死动物。使用 Western blot 和免疫荧光法评估 ER 应激标志物蛋白的表达水平。通过 TUNEL 染色分析细胞凋亡率。使用转棒试验和 Morris 水迷宫评估小鼠的神经功能。
我们的结果表明，轻度低温可显著减轻严重 TBI 后 1 天和 7 天的 ER 应激标志物蛋白，包括 p-eIF2α/eIF2α、ATF4、CHOP 和 IRE-1α，减少损伤区周围的细胞凋亡率。有趣的是，轻度低温还可阻止 CHOP 向核内易位。此外，创伤后轻度低温可显著改善严重 TBI 后的神经功能。
我们的研究结果表明，轻度低温可减轻严重创伤性脑损伤后 ER 应激诱导的细胞凋亡，改善神经功能。
