State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences Fudan University, Shanghai 200032, China.
Neurobiol Dis. 2010 Mar;37(3):711-22. doi: 10.1016/j.nbd.2009.12.010. Epub 2009 Dec 21.
Ethyl pyruvate (EP) is protective in experimental models of many illnesses. This study investigates whether EP can protect against neonatal hypoxic-ischemic (H-I) brain injury. Pre-treatment with EP significantly reduced brain damage at 7 days post-H-I, with 50 mg/kg EP achieving over 50% recovery in tissue loss compared to vehicle-treated animals. Delayed treatment with EP until 30 min after H-I was still neuroprotective. EP-afforded brain protection, together with neurological function improvement, was observed up to 2 months after H-I. We further demonstrated an inhibitory effect of EP on cell death, both in an in vivo model of H-I and in in vitro neuronal cultures subjected to OGD, by reducing calpain activation and calcium dysregulation. Moreover, EP exerted an anti-inflammatory effect in microglia by inhibiting NF-kappaB activation and subsequent release of inflammatory mediators. Taken together, our results suggest that EP confers potent neuroprotection against neonatal H-I brain injury via its anti-cell death and anti-inflammatory actions. EP is a potential novel therapeutic agent for neonatal H-I brain injury.
丙酮酸乙酯（EP）在许多疾病的实验模型中具有保护作用。本研究探讨了 EP 是否可以预防新生儿缺氧缺血（H-I）脑损伤。EP 的预处理显著减轻了 H-I 后 7 天的脑损伤，与 vehicle 处理的动物相比，50mg/kg EP 使组织损失的恢复超过 50%。H-I 后 30 分钟延迟给予 EP 仍具有神经保护作用。EP 提供的脑保护作用，以及神经功能的改善，在 H-I 后 2 个月内均可观察到。我们进一步通过减少钙蛋白酶激活和钙失调，证明了 EP 在体内 H-I 模型和体外神经元培养物中对细胞死亡的抑制作用。此外，EP 通过抑制 NF-κB 激活和随后炎症介质的释放，在小胶质细胞中发挥抗炎作用。总之，我们的结果表明，EP 通过其抗细胞死亡和抗炎作用对新生儿 H-I 脑损伤提供了强大的神经保护作用。EP 是治疗新生儿 H-I 脑损伤的一种有潜力的新型治疗药物。
