Hypoxic-ischemic encephalopathy is a common neonatal brain injury associated with significant morbidity and mortality despite the administration of therapeutic hypothermia (TH). Neonatal seizures and subsequent chronic epilepsy are frequent in this patient population and current treatments are partially effective. We used a neonatal murine hypoxia-ischemia (HI) model to test whether the severity of hippocampal and cortical injury predicts seizure susceptibility 8 days after HI and whether TH mitigates this susceptibility. HI at postnatal day 10 (P10) caused hippocampal injury not mitigated by TH in male or female pups. TH did not confer protection against flurothyl seizure susceptibility at P18 in this model. Hippocampal (R2 = 0.33, p = 0.001) and cortical (R2 = 0.33, p = 0.003) injury directly correlated with seizure susceptibility in male but not female pups. Thus, there are sex-specific consequences of neonatal HI on flurothyl seizure susceptibility in a murine neonatal HI model. Further studies are necessary to elucidate the underlying mechanisms of sex dimorphism in seizure susceptibility after neonatal HI.

中文翻译：

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新生儿缺氧缺血后接受低温治疗的雄性小鼠的癫痫易感性与脑损伤相关。

缺氧缺血性脑病是一种常见的新生儿脑损伤，尽管给予了治疗性低温 (TH)，但仍与显着的发病率和死亡率相关。在该患者群体中，新生儿癫痫发作和随后的慢性癫痫很常见，目前的治疗方法部分有效。我们使用新生小鼠缺氧缺血 (HI) 模型来测试海马和皮质损伤的严重程度是否可以预测 HI 后 8 天的癫痫易感性，以及 TH 是否能减轻这种易感性。出生后第 10 天 (P10) 的 HI 导致雄性或雌性幼崽的 TH 不能减轻海马损伤。在该模型中，TH 并未在 P18 处对氟乙基癫痫发作易感性提供保护。海马体 (R2 = 0.33, p = 0.001) 和皮质 (R2 = 0.33, p = 0。003) 损伤与雄性幼崽的癫痫易感性直接相关，但与雌性幼崽无关。因此，在小鼠新生儿 HI 模型中，新生儿 HI 对氟乙基癫痫发作易感性存在性别特异性后果。需要进一步的研究来阐明新生儿 HI 后癫痫易感性中性别二态性的潜在机制。