Increased PINK1/Parkin-mediated mitophagy explains the improved brain protective effects of slow rewarming following hypothermia after cardiac arrest in rats.Cerebral ischemia-reperfusion (I/R) after cardiac arrest (CA) induces mitochondrial dysfunction, and the timely removal of damaged mitochondria by mitophagy is reported to protect against cerebral I/R injury.  Therapeutic hypothermia (TH) has become an important component of postresuscitation care for patients who return to spontaneous circulation after CA.  Here, we investigated the effects of different rewarming rates and whether mitophagy is involved in rewarming.  After 5 min of asphyxial CA following 4 h of cooling, Sprague-Dawley rats were randomized into the normothermia, hypothermia, slow rewarming (0.5 °C/h) and fast rewarming (4 °C/h) groups.  The hypothermia group was kept cool until tissue harvest, the rewarming duration for the slow rewarming group and fast rewarming group was 6 h and 45 min, respectively.  We found that slowly rewarmed rats had better survival at 72 h than normothermic rats and fast-rewarmed rats (70%, 25.71%, and 50%, respectively) and higher neurological deficit scores (NDSs), in which the medians were 57.33, 26, and 28.83, respectively.  In addition, we explored the underlying mechanism during this process and found that PINK1/Parkin-mediated mitophagy was activated during hypothermia in the slow rewarming group but was inhibited in the fast rewarming group.  Overall, our results highlighted a neuroprotective role of PINK1/Parkin-mediated mitophagy during slow rewarming after hypothermia.
THERM