Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux
Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux
复制标题
清除血液谷氨酸以增强脑到血液谷氨酸的流出
DOI：
10.3892/mmr.2013.1793
复制
发表时间：
2014-01-01
影响因子：
3.4
通讯作者：
Wang, Yin
中科院分区：
文献类型：
--
作者：
Li, Yunhong;Hou, Xiaolin;Wang, Yin
脑间质液中过量谷氨酸的存在表征了脑的几种急性病理状况，包括创伤性脑损伤和中风。已经证明，可以通过降低血液谷氨酸水平来消除大脑中过量的谷氨酸，并因此加速大脑到血液的谷氨酸流出。通过在各自的谷氨酸共底物存在下活化血液驻留酶来完成该过程是可行的。在本研究中，研究了几种谷氨酸辅助底物和辅助因子，试图确定降低血液谷氨酸水平的最佳条件。1 mM丙酮酸和草酰乙酸（Pyr/Oxa）的混合物给药1小时可使血液谷氨酸水平降低50%。向该混合物中添加硫辛酰胺导致血液谷氨酸水平进一步降低> 80%。此外，体内实验表明，硫辛酰胺与Pyr/Oxa一起能够比单独的Pyr/Oxa更大程度地降低血液谷氨酸水平，因此，这增强了谷氨酸从大脑到血液的流出。这些结果可能概述了一种新的神经保护策略，其在各种神经退行性疾病中清除过量脑谷氨酸的有效性增加。
The presence of excess glutamate in the brain interstitial fluid characterizes several acute pathological conditions of the brain, including traumatic brain injury and stroke. It has been demonstrated that it is possible to eliminate excess glutamate in the brain by decreasing blood glutamate levels and, accordingly, accelerating the brain-to-blood glutamate efflux. It is feasible to accomplish this process by activating blood resident enzymes in the presence of the respective glutamate cosubstrates. In the present study, several glutamate cosubstrates and cofactors were studied in an attempt to identify the optimal conditions to reduce blood glutamate levels. The administration of a mixture of 1 mM pyruvate and oxaloacetate (Pyr/Oxa) for 1 h decreased blood glutamate levels by 50%. The addition of lipoamide to this mixture resulted in a further reduction in blood glutamate levels of >80%. In addition, in vivo experiments showed that lipoamide together with Pyr/Oxa is able to decrease blood glutamate levels to a greater extent than Pyr/Oxa alone, and accordingly, this enhances the glutamate efflux from the brain to the blood. These results may outline a novel neuroprotective strategy with increased effectiveness for the removal of excess brain glutamate in various neurodegenerative conditions.