Background Hypoxia–ischemia (HI) is the most common cause of brain injury in newborns and the survivors often develop cognitive and sensorimotor disabilities that undermine the quality of life. In the current study, we examined the effectiveness of flupirtine, a potassium channel opener, shown previously in an animal model to have strong anti-neonatal-seizure efficacy, to provide neuroprotection and alleviate later-life disabilities caused by neonatal hypoxic–ischemic injury. Methods The rats were treated with a single dose of flupirtine for 4 days following HI induction in 7-day-old rats. The first dose of flupirtine was given after the induction of HI and during the reperfusion period. The effect of treatment was examined on acute and chronic brain injury, motor functions, and cognitive abilities. Results Flupirtine treatment significantly reduced HI-induced hippocampal and cortical tissue loss at acute time point. Furthermore, at chronic time point, flupirtine reduced contralateral hippocampal volume loss and partially reversed learning and memory impairments but failed to improve motor deficits. Conclusion The flupirtine treatment regimen used in the current study significantly reduced brain injury at acute time point in an animal model of neonatal hypoxic–ischemic encephalopathy. However, these neuroprotective effects were not persistent and only modest improvement in functional outcomes were observed at chronic time points.

中文翻译：

---

钾通道开放剂对新生儿缺氧缺血性损伤动物模型脑损伤和神经系统结局的影响

背景 缺氧-缺血 (HI) 是新生儿脑损伤的最常见原因，幸存者经常会出现认知和感觉运动障碍，从而影响生活质量。在目前的研究中，我们检查了氟吡汀（一种钾通道开放剂）的有效性，先前在动物模型中显示具有强大的抗新生儿癫痫发作功效，可提供神经保护并减轻新生儿缺氧缺血性损伤引起的晚年残疾。方法 在 7 日龄大鼠 HI 诱导后，用单剂量氟吡汀治疗大鼠 4 天。在 HI 诱导后和再灌注期间给予第一剂氟吡汀。检查治疗对急性和慢性脑损伤、运动功能和认知能力的影响。结果氟吡汀治疗在急性时间点显着减少了 HI 诱导的海马和皮质组织损失。此外，在慢性时间点，氟吡汀减少了对侧海马体积损失并部分逆转了学习和记忆障碍，但未能改善运动缺陷。结论 本研究中使用的氟吡汀治疗方案可显着减少新生儿缺氧缺血性脑病动物模型的急性时间点脑损伤。然而，这些神经保护作用不是持久的，在慢性时间点仅观察到功能结果的适度改善。氟吡汀减少了对侧海马体积损失并部分逆转了学习和记忆障碍，但未能改善运动缺陷。结论 本研究中使用的氟吡汀治疗方案可显着减少新生儿缺氧缺血性脑病动物模型的急性时间点脑损伤。然而，这些神经保护作用不是持久的，在慢性时间点仅观察到功能结果的适度改善。氟吡汀减少了对侧海马体积损失并部分逆转了学习和记忆障碍，但未能改善运动缺陷。结论 本研究中使用的氟吡汀治疗方案可显着减少新生儿缺氧缺血性脑病动物模型急性时间点的脑损伤。然而，这些神经保护作用不是持久的，在慢性时间点仅观察到功能结果的适度改善。