Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Am J Emerg Med. 2013 Jan;31(1):154-60. doi: 10.1016/j.ajem.2012.06.033. Epub 2012 Sep 11.
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.
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.
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.
Postischemic administration of low-dose 17β-estradiol appears to be neuroprotective after transient global ischemia, and its effect is potentiated by therapeutic hypothermia.
低温治疗目前被认为是心脏骤停后治疗全脑缺血损伤唯一有效的方法。大量关于 17β-雌二醇神经保护作用的研究因给药途径和剂量的不同而得出相互矛盾的结果。在此，我们研究了缺血后给予 17β-雌二醇联合低温治疗的神经保护作用。
21 只大鼠随机分为 4 组：对照组（I 组）、低温治疗组（II 组）、17β-雌二醇治疗组（III 组）和低温治疗联合 17β-雌二醇治疗组（IV 组）。每组有 1 只大鼠作为假手术组。除假手术组大鼠外，其余大鼠均采用四血管阻断法制作短暂全脑缺血模型 20 分钟。II 组和 IV 组于缺血后 2 小时内维持体温在 33℃，III 组和 IV 组于大鼠腹腔内给予 17β-雌二醇（10μg/kg）。于缺血后 72 小时评估大鼠的神经功能缺损评分和海马 CA1 区神经元损伤。
各组大鼠的神经功能缺损评分无明显差异。I 组海马 CA1 区正常神经元百分比为 7.32%±0.88%，II 组为 53.65%±2.52%，III 组为 51.6%±3.44%，IV 组为 79.79%±1.6%。联合治疗组的神经保护作用明显强于单一治疗组，提示低温和 17β-雌二醇具有协同作用发挥神经保护作用。
短暂全脑缺血后缺血后给予低剂量 17β-雌二醇具有神经保护作用，低温治疗可增强其作用。
