Exocytosis, calcium oscillations, and novel glutamate release blockers as resolved by rapid superfusion.
Exocytosis, calcium oscillations, and novel glutamate release blockers as resolved by rapid superfusion.
复制标题
胞吐作用、钙振荡和新型谷氨酸释放阻滞剂可通过快速灌注解决。
DOI：
10.1111/j.1749-6632.1994.tb26635.x
复制
发表时间：
1994
影响因子：
5.2
通讯作者：
Subbarao,K
中科院分区：
文献类型：
--
作者：
Goldin,SM;Finch,EA;Reddy,NL;Hu,LY;Subbarao,K
脑缺血损伤，如中风或创伤性脑损伤，从去极化神经末梢产生过量和长时间的谷氨酸释放。阻断谷氨酸突触后作用的药物已被研究作为限制缺血性脑损伤的候选药物。谷氨酸受体n -甲基+-天冬氨酸（NMDA）敏感亚类拮抗剂的明确适应症是急性局灶性脑缺血的治疗，如中风和创伤性脑损伤。NMDA拮抗剂在局灶性脑缺血模型（如大鼠大脑中动脉闭塞（MCAO）模型）中非常有效，但在全局性脑缺血模型中效果较差。相反，非nmda谷氨酸受体拮抗剂，如NBQX[2,3 -二羟基-6-硝基-7-磺胺酰基-苯并(f)喹啉]在大鼠全脑缺血模型中非常有效，但在局灶性脑缺血模型中效果较差。通过阻断控制胞吐的突触前电压敏感离子通道来阻止谷氨酸释放，可能在病理生理级联的早期阶段中止导致神经细胞死亡的过程。4.6* 7谷氨酸释放阻滞剂，通过在过程的早期阶段起作用，应防止NMDA和非NMDA谷氨酸受体亚类的过度激活，并可能联合使用
Ischemic insults to the brain, as occur in stroke or traumatic brain injury, produce excessive and prolonged release of glutamate from depolarized nerve terminals.'. 2 Agents that block the postsynaptic actions of glutamate have been investigated as candidates for the limitation of ischemic brain damage. A clear indication for the therapeutic use of antagonists of the N-methyl+-aspartate (NMDA)-sensitive subclass of glutamate receptors is in the acute treatment of focal cerebral ischemia, as occurs in stroke and traumatic brain injury. NMDA antagonists are highly effective in models of focal cerebral ischemia, such as the rat middle cerebral artery occlusion (MCAO) model, 3 but appear to be less effective in models of global cerebral i~ chemia.~ In contrast, non-NMDA glutamate receptor antagonists such as NBQX [2, 3-di-hydroxy-6-nitro-7-sulfamoyl-benzo (f) quinoxaline] are highly effective in rat models of global cerebral is~ hemia,~ but are much less effective in models of focal cerebral ischemia.Prevention of glutamate release by blockade of the presynaptic voltage-sensitive ion channels controlling exocytosis may, at an early stage in the pathophysiological cascade, abort the process leading to nerve cell death. 4.6* 7 A blocker of glutamate release, by acting at an earlier stage of the process, should prevent excessive activation of both NMDA and non-NMDA glutamate receptor subclasses and may combine