Argon: long term effects after transient middle artery occlusion; the role of ERK 1/2 activation; the effect on regional cerebral glucose metabolism on neuronal viability

氩气：短暂中动脉闭塞后的长期影响；

• 批准号: 226421327
• 负责人: Professor Dr. Mark Coburn
• 金额: --
• 依托单位: Institut für Neuropathologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/226421327?language=en
• 关键词: Argon; long; term; effects; after

Originally thought to be chemically inert, the noble gases xenon, argon and helium have repeatedly exhibited remarkable biological properties. Xenon is a well known anaesthetic and, has demonstrated in various models of neuronal injury, an effective neuroprotectant. Compared to xenon, argon presents a number of pharmacodynamic distinctions. In particular, its lack of sedative properties may actually be advantageous as it allows administration to patients with neurological injury without overlooking their actual neurological status. A striking second difference involves cost and consequent ease of administration: Argon, the third most abundant element in our atmosphere and about one hundred-fold more cost effective than xenon, may be easily applied perioperatively and in intensive care units. Most important, our group has recently demonstrated that argon conveys neuroprotective effects in in vitro models of traumatic and ischemic brain injury. In consequence, we tested the neuroprotective potential of argon when applied during cerebral ischemia in an in vivo model of transient middle cerebral artery occlusion (tMCAO). We were able to demonstrate a significant reduction in overall damaged brain volume and neurologic deficit twenty-four hours after reperfusion. Ultimately, we were able to demonstrate that argon enhanced ERK 1/2 activity in microglia via the upstream kinase MEK in vitro. Within the scope of this grant application we will examine the long term effects of argon in a well established tMCAO model. Specifically, we will assess the effect of argon on the inflammatory and regenerative response to brain injury and the role of extracellular signal-regulated kinase (ERK) activation. Furthermore, we will study whether argon modulates regional cerebral metabolic rate of glucose (rCMRglc) and neuronal viability by employing various established tracers for autoradiography.

惰性气体氙、氩和氦最初被认为具有化学惰性，但它们却多次表现出显着的生物特性。氙是一种众所周知的麻醉剂，并且已在各种神经元损伤模型中证明是一种有效的神经保护剂。与氙气相比，氩气具有许多药效学差异。特别是，它缺乏镇静特性实际上可能是有利的，因为它允许对神经损伤患者进行给药，而不会忽视他们的实际神经状态。第二个显着的差异涉及成本和随之而来的管理便利性：氩是大气中第三丰富的元素，其成本效益比氙高约一百倍，可以在围手术期和重症监护病房中轻松使用。最重要的是，我们的小组最近证明，氩气在创伤性和缺血性脑损伤的体外模型中具有神经保护作用。因此，我们在短暂性大脑中动脉闭塞 (tMCAO) 体内模型中测试了脑缺血期间应用氩气的神经保护潜力。我们能够证明，再灌注二十四小时后，总体受损脑容量和神经功能缺损显着减少。最终，我们能够在体外证明氩气通过上游激酶 MEK 增强小胶质细胞中的 ERK 1/2 活性。在本次拨款申请的范围内，我们将在完善的 tMCAO 模型中研究氩气的长期影响。具体来说，我们将评估氩气对脑损伤炎症和再生反应的影响以及细胞外信号调节激酶 (ERK) 激活的作用。此外，我们将通过使用各种已建立的放射自显影示踪剂来研究氩气是否调节局部脑葡萄糖代谢率（rCMRglc）和神经元活力。