The study of focal mild hypothermia on prolonging the therapeutic time window after cerebral infarct in rats

Objective To study whether focal mild hypothermia can prolong the therapeutic time window in ischemic stroke, and inquire into the protection mechanisms of focal mild hypothermia on cerebral ischemia. Methods The focal cerebral ischemia and reperfusion model of rats was achieved by intraluminal middle cerebral artery occlusion (MCAO). The adult rats were randomly divided into sham-operation group, normothermia ischemia and reperfusion group and hypothermia ischemia and reperfusion group. The two ischemic groups were respectively further divided into 5 subgroups (subjected ischemia for 2, 3, 6, 8 and 12 h respectively and then all reperfused for 4 h, n=14 per time point). Brain mild hypothermia was achieved 30 minutes after ischemia and maintained to reperfusion period. The neurological deficit scores were assessed. The infarct volumes were evaluated by TTC staining and measured with a computerized image analysis system. TUNEL method was used to observe the neuron apoptosis. The expressions of NF-κBp65 and NF-κBP65mRNA were detected by immunohistochemistry and hybridation in situ. Results The infarct volumes of hypothermia group were respectively (57.39±37.62) mm~3, (74.09±61.00) mm~3, (81.26±25.46) mm~3, (87.43±54.81) mm~3 and (111.10±43.67) mm~3, which saw significant reductions of 63%, 55%, 56%, 70% and 63% as compared with the normothermia group. In comparison with the normothermia group, focal mild hypothermia also greatly reduced the neurological deficit scores (P0.05 or P0.01), and obviously inhibited the expressions of NF-κBp65 and apoptotic neurons in penumbra (P0.05 or P0.01). Conclusions The focal mild hypothermia should possibly prolong the therapeutic time window of thrombolytic intervention in ischemic stroke. The focal mild hypothermia might reduce the infarct volume and accelerate the recovery of the neurological outcome, which might be related to inhibition, activation and translocation of the NF-κB, and thus might produce the anti-apoptosis function.