Combination treatment with 17β-estradiol and therapeutic hypothermia for transient global cerebral ischemia in rats

Objective: Therapeutic hypothermia is now regarded as the only effective treatment of global ischemic injury after cardiac arrest. Numerous studies of the neuroprotective effects of 17β-estradiol have yielded conflicting results depending on administration route and dose. Herein, we investigated the neuroprotective effect of postischemic 17β-estradiol administration combined with therapeutic hypothermia. Methods: Twenty-one rats were randomly divided into 4 groups: control (group I), therapeutic hypothermia (group II), 17β-estradiol treatment (group III), and therapeutic hypothermia combined with 17β-estradiol treatment (group IV). One rat was assigned to a sham operation group. With the exception of the sham-operated rat, all animals underwent transient global cerebral ischemia for 20 minutes by the 4-vessel occlusion method. Hypothermia was maintained at 33°C for 2 hours in groups II and IV, and 17β-estradiol (10 μg/kg) was intraperitoneally administered to rats in groups III and IV. Neurologic deficit scores and hippocampal cornu ammonis 1 neuronal injury were assessed 72 hours postischemia. Results: The neurologic deficit score was not significantly different among the groups. The percentage of normal neurons in the hippocampal cornu ammonis 1 was 7.32% ± 0.88% in group I, 53.65% ± 2.52% in group II, 51.6% ± 3.44% in group III, and 79.79% ± 1.6% in group IV. The neuroprotective effect in the combined treatment group was markedly greater than in the single treatment groups, which suggests that hypothermia and 17β-estradiol work synergistically to exert neuroprotection. Conclusion: Postischemic administration of low-dose 17β-estradiol appears to be neuroprotective after transient global ischemia, and its effect is potentiated by therapeutic hypothermia.