Role of PERK‐mediated pathway in the effect of mild hypothermia after cerebral ischaemia/reperfusion

Abstract

BackgroundHypothermia is an effective method of reducing brain injury caused by a variety of neurological insults. It is aimed to elucidate whether a change in the expression of PERK‐mediated pathway proteins is an indicator of the neuroprotective effect of mild hypothermia after cerebral ischaemia/reperfusion.MethodsOne hundred and ninety‐two male C57BL/6 mice were randomly divided into three groups: a sham group, a cerebral normothermic ischaemia/reperfusion (I/R) group and a cerebral hypothermic I/R group. A cerebral ischaemia model was established by ligating the bilateral common carotid artery for 15 min. Mice in the hypothermia group stayed in a cage that was set at 33°C, sprayed with a spray of 70% ethanol, and blown with two high‐speed fans. The state of neurons was assessed on micropreparations stained with haematoxylin–eosin and TUNEL. The expressions of GRP78, p‐perk, p‐eif2α, ATF4 and CHOP were measured by western blot analysis 6, 12, 24 and 72 h after reperfusion.ResultsThe number of surviving cells was significantly higher in the hypothermia group than in the group without hypothermia (p < .05). The GRP78 expression in the hypothermia group was statistically higher (p < .05) than in the ischaemia/reperfusion group. Optical densities of p‐perk, p‐eif2α and ATF4 in hippocampus CA1 neurons ischaemia were statistically significantly lower in the hypothermia group than in the ischaemia/reperfusion group (p < .05). The CHOP expression in the hypothermia group was statistically lower (p < .05) than in the ischaemia/reperfusion group.ConclusionMild hypothermia for 6 h promoted moderate neuroprotection by mediating the expression of GRP78, p‐PERK, p‐eIF2α, ATF4 and CHOP.