Department of Neurology and Neurosurgery - UNIFESP São Paulo, Brazil.
Neurochem Int. 2011 Feb;58(3):385-90. doi: 10.1016/j.neuint.2010.12.014. Epub 2010 Dec 24.
Recent research data have shown that systemic administration of pyruvate and oxaloacetate causes an increased brain-to-blood glutamate efflux. Since increased release of glutamate during epileptic seizures can lead to excitotoxicity and neuronal cell death, we tested the hypothesis that glutamate scavenging mediated by pyruvate and oxaloacetate systemic administration could have a neuroprotective effect in rats subjected to status epilepticus (SE). SE was induced by a single dose of pilocarpine (350mg/kgi.p.). Thirty minutes after SE onset, a single dose of pyruvate (250mg/kgi.p.), oxaloacetate (1.4mg/kgi.p.), or both substances was administrated. Acute neuronal loss in hippocampal regions CA1 and hilus was quantitatively determined five hours after SE onset, using the optical fractionator method for stereological cell counting. Apoptotic cascade in the hippocampus was also investigated seven days after SE using caspase-1 and -3 activity assays. SE-induced neuronal loss in CA1 was completely prevented in rats treated with pyruvate plus oxaloacetate. The SE-induced caspase-1 activation was significantly reduced when rats were treated with oxaloacetate or pyruvate plus oxaloacetate. The treatment with pyruvate and oxaloacetate caused a neuroprotective effect in rats subjected to pilocarpine-induced SE.
最近的研究数据表明，丙酮酸和草酰乙酸的全身给药会导致脑内谷氨酸向血液的流出增加。由于癫痫发作期间谷氨酸的释放增加可能导致兴奋性毒性和神经元细胞死亡，我们测试了这样一个假设，即丙酮酸和草酰乙酸的全身给药介导的谷氨酸清除作用可能对癫痫持续状态（SE）大鼠具有神经保护作用。SE 通过单次腹腔注射匹鲁卡品（350mg/kg）诱导。SE 发作后 30 分钟，单次给予丙酮酸（250mg/kg）、草酰乙酸（1.4mg/kg）或两种物质。SE 发作后 5 小时，使用光学分束器方法进行立体细胞计数定量测定海马区 CA1 和门区的急性神经元丢失。SE 后 7 天，还通过半胱氨酸天冬氨酸蛋白酶-1 和 -3 活性测定研究了海马中的凋亡级联。用丙酮酸加草酰乙酸治疗可完全防止 SE 诱导的 CA1 神经元丢失。当用草酰乙酸或丙酮酸加草酰乙酸治疗时，SE 诱导的半胱氨酸天冬氨酸蛋白酶-1 激活显著减少。用丙酮酸和草酰乙酸治疗对匹鲁卡品诱导的 SE 大鼠具有神经保护作用。
