The Parkinson's and Movement Disorder Research Laboratory, Long Beach Memorial Medical Center, Long Beach, California, United States of America.
PLoS One. 2013 Apr 8;8(4):e60309. doi: 10.1371/journal.pone.0060309. Print 2013.
It has been reported that both activation of N-methyl-D-aspartate receptors and acid-sensing ion channels during cerebral ischemic insult contributed to brain injury. But which of these two molecular targets plays a more pivotal role in hypoxia-induced brain injury during ischemia is not known. In this study, the neuroprotective effects of an acid-sensing cation channel blocker and an N-methyl-D-aspartate receptor blocker were evaluated in a rat model of cardiac arrest-induced cerebral hypoxia. We found that intracisternal injection of amiloride, an acid-sensing ion channel blocker, dose-dependently reduced cerebral hypoxia-induced neurodegeneration, seizures, and audiogenic myoclonic jerks. In contrast, intracisternal injection of memantine, a selective uncompetitive N-methyl-D-aspartate receptor blocker, had no significant effect on cerebral hypoxia-induced neurodegeneration, seizure and audiogenic myoclonic jerks. Intracisternal injection of zoniporide, a specific sodium-hydrogen exchanger inhibitor, before cardiac arrest-induced cerebral hypoxia, also did not reduce cerebral hypoxia-induced neurodegeneration, seizures and myoclonic jerks. These results suggest that acid-sensing ion channels play a more pivotal role than N-methyl-D-aspartate receptors in mediating cerebral hypoxia-induced brain injury during ischemic insult.
据报道，在脑缺血损伤过程中，N-甲基-D-天冬氨酸受体和酸感应离子通道的激活都有助于脑损伤。但在缺血期间缺氧诱导的脑损伤中，这两个分子靶点中哪一个起更关键的作用尚不清楚。在这项研究中，我们评估了酸感应阳离子通道阻滞剂和 N-甲基-D-天冬氨酸受体阻滞剂在心脏骤停诱导的脑缺氧大鼠模型中的神经保护作用。我们发现，蛛网膜下腔注射酸感应离子通道阻滞剂阿米洛利可剂量依赖性地减轻脑缺氧诱导的神经变性、癫痫发作和听源性肌阵挛性抽搐。相比之下，蛛网膜下腔注射选择性非竞争性 N-甲基-D-天冬氨酸受体阻滞剂美金刚对脑缺氧诱导的神经变性、癫痫发作和听源性肌阵挛性抽搐没有显著影响。心脏骤停诱导脑缺氧前蛛网膜下腔注射特异性钠-氢交换抑制剂扎尼普隆也不能减轻脑缺氧诱导的神经变性、癫痫发作和肌阵挛性抽搐。这些结果表明，在缺血性损伤过程中，酸感应离子通道在介导脑缺氧诱导的脑损伤方面比 N-甲基-D-天冬氨酸受体发挥更关键的作用。
