Each year there are approximately 7000 out of hospital cardiac arrests in the pediatric population, with 30% resuscitation rate and a 6-10% rate of survival to hospital discharge. Survivors of cardiac arrest exhibit learning and memory deficits that are devastating during the school years. Delayed neuronal cell death occurs in the hippocampus following cardiac arrest and likely contributes to memory impairments. Circulating endogenous estrogen in young adult females has been shown to provide protection against ischemic cell death, as does chronic exogenous administration of 17β-estradiol (E2). Chronic estrogen benefit can have undesirable feminizing effects, particularly in pre-adolescents. Here, we tested if a single-dose of E2 is neuroprotective in our pediatric cardiac arrest mouse model performed in juvenile mice. We subjected P21P25 C57Blk6 male and female mice to 8 min of cardiac arrest followed by cardiopulmonary resuscitation (CA/CPR). This developmental stage preceded the hormonal onset and serum estradiol and testosterone levels were not different in males and females. A single dose of E2 (100μg/kg) or vehicle was administered 30 min after resuscitation. Neuronal cell death measured 3 days after CA/CPR showed reduced hippocampal cell death in E2-treated females, but not males. Benefit of E2 in females was blocked by the P38 MAPK inhibitor, SB203580. Hippocampal-dependent memory function was equally impaired in E2-and vehicle-treated females measured in the contextual fear conditioning task at 7 days. Our findings demonstrate female-specific transient neuroprotection with E2 that does not provide sustained functional benefit.

中文翻译：

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心脏骤停和心肺复苏后，单剂17β-雌二醇可为雌性幼年小鼠提供短暂的神经保护。

每年在儿科人群中约有7000次心脏骤停，其中复苏率30％，出院生存率6-10％。心脏骤停的幸存者在学习期间表现出毁灭性的学习和记忆缺陷。延迟的神经元细胞死亡发生在心脏骤停后的海马中，并可能导致记忆障碍。研究表明，成年女性中循环内源性雌激素可提供保护作用，以防止缺血性细胞死亡，慢性外源性给予17β-雌二醇（E2）也是如此。慢性雌激素的益处可能具有不良的女性化作用，尤其是在青春期前。在这里，我们测试了单剂量E2在少年小鼠中进行的小儿心脏骤停小鼠模型中是否具有神经保护作用。我们对P21P25 C57Blk6雄性和雌性小鼠进行了8分钟的心脏骤停，然后进行了心肺复苏（CA / CPR）。这个发育阶段是在荷尔蒙发作之前进行的，男性和女性的血清雌二醇和睾丸激素水平没有差异。复苏后30分钟给予单剂量E2（100μg/ kg）或赋形剂。CA / CPR 3天后测量的神经元细胞死亡显示，经E2处理的雌性海马细胞死亡减少，而雄性则没有。P38 MAPK抑制剂SB203580阻止了E2在雌性中的作用。在7天的情境恐惧调节任务中，E2和接受媒介物治疗的女性的海马依赖性记忆功能均受损。我们的研究结果表明，E2对女性的短暂性神经保护作用并不能提供持续的功能益处。