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

ObjectiveTherapeutic 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.MethodsTwenty-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.ResultsThe 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.ConclusionPostischemic administration of low-dose 17β-estradiol appears to be neuroprotective after transient global ischemia, and its effect is potentiated by therapeutic hypothermia.