Dynamin-related
protein 1 (Drp1) regulates mitochondrial fission, it has been proven that inhibition of Drp1 by
mdivi-1 improves survival and attenuates cerebral ischemic injury after
cardiac arrest. In this study, we compared the effects of Drp1 inhibition with
therapeutic hypothermia on post-
resuscitation neurologic injury in a rat model of
cardiac arrest. Rats were randomized into 4 groups:
mdivi-1 treatment group (n = 39), hypothermic group (n = 38), normothermic group (n = 41), and
sham group (n = 12). The rats in the
mdivi-1 treatment group were received intravenously 1.2 mg/kg of
mdivi-1 at 1 minute after the return of spontaneous circulation (ROSC). In rats in
hypothermia group, rapid cooling was initiated at 5 minutes after
resuscitation, and the core temperature was maintained to 33 ± 0.5°C for 2 hours. The results showed that both Drp1 inhibition and
therapeutic hypothermia increased 3-day survival time (all P <0.05) and improved neurologic function up to 72 hours post
cardiac arrest. In addition, both Drp1 inhibition and
therapeutic hypothermia decreased cell injury, apoptosis in hippocampal cornu ammonis 1 region and brain
mitochondrial dysfunction including
adenosine triphosphate production,
reactive oxygen species and mitochondrial membrane potential after
cardiac arrest. Moreover,
therapeutic hypothermia decreased mitochondrial Drp1 expression and mitochondrial fission after
cardiac arrest. In conclusion, inhibition of Drp1 has a similar effect to
therapeutic hypothermia on neurologic outcome after
resuscitation in this
cardiac arrest rat model, and the
neuroprotective effects of
therapeutic hypothermia are associated with inhibition of mitochondrial fission.