Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovak Republic.
Neurochem Int. 2013 May;62(6):854-60. doi: 10.1016/j.neuint.2013.02.019. Epub 2013 Feb 26.
In the clinic delayed post-conditioning would represent an attractive strategy for the survival of vulnerable neurons after an ischemic event. In this paper we studied the impact of ischemia and delayed post-conditioning on blood and brain tissue concentrations of glutamate and protein synthesis. We designed two groups of animals for analysis of brain tissues and blood after global ischemia and post-conditioning, and one for analysis of blood glutamate after transient focal ischemia. Our results showed elevated blood glutamate in two models of transient brain ischemia and decreases in blood glutamate to control in the first 20min of post-conditioning recirculation followed by a consecutive drop of about 20.5% on the first day. Similarly, we recorded reduced protein synthesis in hippocampus and cortex 2 and 3days after ischemia. However, increased glutamate was registered only in the hippocampus. Post-conditioning improves protein synthesis in CA1 and dentate gyrus and, surprisingly, leads to 50% reduction in glutamate in whole hippocampus and cortex. In conclusion, ischemia leads to meaningful elevation of blood and tissue glutamate. Post-conditioning activates mechanisms resulting in rapid elimination of glutamate from brain tissue and/or in the circulatory system that could otherwise impede brain-to-blood glutamate efflux mechanisms. Moreover, post-conditioning induces protein synthesis renewing in ischemia affected tissues that could also contribute to elimination of excitotoxicity. In addition, the potential of glutamate for monitoring the progress of ischemia and efficacy of therapy was shown.
在临床上，延迟后处理对于缺血事件后易损神经元的存活可能是一种有吸引力的策略。本文研究了缺血和延迟后处理对谷氨酸和蛋白质合成的血液和脑组织浓度的影响。我们设计了两组动物进行全脑缺血和后处理后的脑组织和血液分析，以及一组动物进行短暂局灶性缺血后血液谷氨酸分析。我们的结果显示，两种短暂性脑缺血模型的血液谷氨酸升高，在再灌注后的前 20 分钟内，血液谷氨酸降低到对照水平，然后在第一天连续下降约 20.5%。同样，我们记录到缺血后 2 天和 3 天海马体和皮质 2、3 区的蛋白质合成减少。然而，只有在海马体中记录到谷氨酸增加。后处理可改善 CA1 和齿状回的蛋白质合成，令人惊讶的是，可使整个海马体和皮质的谷氨酸减少 50%。总之，缺血导致血液和组织谷氨酸显著升高。后处理激活了一些机制，可使谷氨酸迅速从脑组织和/或循环系统中清除，否则这些机制会阻碍脑-血谷氨酸外排机制。此外，后处理诱导缺血影响组织中的蛋白质合成更新，这也有助于消除兴奋性毒性。此外，还显示了谷氨酸在监测缺血进展和治疗效果方面的潜力。
