Moderate brain hypothermia started before resuscitation improves survival and neurobehavioral outcomes after CA/CPR in mice.

AIM OF THE STUDY

No definitive experimental or clinical evidence exists whether brain hypothermia before, rather than during or after, resuscitation can reduce hypoxic-ischemic brain injury following cardiac arrest/cardiopulmonary resuscitation (CA/CPR) and improve outcomes. We examined the effects of moderate brain hypothermia before resuscitation on survival and histopathological and neurobehavioral outcomes in a mouse model.

METHODS

Adult C57BL/6 male mice (age: 8-12 weeks) were subjected to 8-min CA followed by CPR. The animals were randomly divided into sham, normothermia (NT; brain temperature 37.5 °C), and extracranial hypothermia (HT; brain temperature 28-32 °C) groups. The hippocampal CA1 was assessed 7 day after resuscitation by histochemical staining. Neurobehavioral outcomes were evaluated by the Barnes maze (BMT), openfield (OFT), rotarod, and light/dark (LDT) tests. Cleaved caspase-3 and heat shock protein 60 (HSP70) levels were investigated by western blotting.

RESULTS

The HT group exhibited higher survival and lower CA1 neuronal injury than did the NT group. HT mice showed improved spatial memory in the BMT compared with NT mice. NT mice travelled a shorter distance in the OFT and tended to spend more time in the light compartment in the LDT than did sham and HT mice. The levels of cleaved caspase-3 and HSP70 were non-significantly higher in the NT than in the sham and HT groups.

CONCLUSIONS

Moderate brain hypothermia before resuscitation improved survival and reduced histological neuronal injury, spatial memory impairment, and anxiety-like behaviours after CA/CPR in mice.