Kawakita Fumihiro, Kanamaru Hideki, Asada Reona, Suzuki Yume, Nampei Mai, Nakajima Hideki, Oinaka Hiroki, Suzuki Hidenori
Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.
Histol Histopathol. 2022 Nov;37(11):1041-1051. doi: 10.14670/HH-18-509. Epub 2022 Sep 6.
Aneurysmal subarachnoid hemorrhage (SAH) is a stroke type with a high rate of mortality and morbidity. Post-SAH brain injury as a determinant of poor outcome is classified into the following two types: early brain injury (EBI) and delayed cerebral ischemia (DCI). EBI consists of various acute brain pathophysiologies that occur within the first 72 hours of SAH in a clinical setting. The underlying mechanisms of DCI are considered to be cerebral vasospasm or microcirculatory disturbance, which develops mostly 4 to 14 days after clinical SAH. Glutamate is the principal neurotransmitter in the central nervous system, but excessive glutamate is known to induce neurotoxicity. Experimental and clinical studies have revealed that excessive glutamates are released after SAH. In addition, many studies have reported the relationships between excessive glutamate release or overactivation of glutamate receptors and excitotoxicity, cortical spreading depolarization, seizure, increased blood-brain barrier permeability, neuroinflammation, microthrombosis formation, microvasospasm, cerebral vasospasm, impairments of brain metabolic supply and demand, impaired neurovascular coupling, and so on, all of which potentially contribute to the development of EBI or DCI. As glutamates always exert their functions through one or more of 4 major receptors of glutamates, it would be valuable to know the mechanisms as to how glutamates cause these pathologies, and the possibility that a glutamate receptor antagonist may block the pathologies. To prevent the mechanistic steps leading to glutamate-mediated neurotoxicity may ameliorate SAH-induced brain injuries and improve the outcomes. This review addresses the current knowledge of glutamate-mediated neurotoxicity, focusing on EBI and DCI after SAH.
动脉瘤性蛛网膜下腔出血（SAH）是一种死亡率和发病率都很高的中风类型。作为不良预后决定因素的SAH后脑损伤可分为以下两种类型：早期脑损伤（EBI）和迟发性脑缺血（DCI）。EBI包括在临床环境中SAH后72小时内发生的各种急性脑病理生理过程。DCI的潜在机制被认为是脑血管痉挛或微循环紊乱，其大多在临床SAH后4至14天出现。谷氨酸是中枢神经系统中的主要神经递质，但已知过量的谷氨酸会诱发神经毒性。实验和临床研究表明，SAH后会释放过量的谷氨酸。此外，许多研究报道了过量谷氨酸释放或谷氨酸受体过度激活与兴奋性毒性、皮层扩散性去极化、癫痫发作、血脑屏障通透性增加、神经炎症、微血栓形成、微血管痉挛、脑血管痉挛、脑代谢供需受损、神经血管耦合受损等之间的关系，所有这些都可能导致EBI或DCI的发生。由于谷氨酸总是通过4种主要谷氨酸受体中的一种或多种发挥作用，了解谷氨酸如何导致这些病理变化的机制以及谷氨酸受体拮抗剂可能阻断这些病理变化的可能性将是很有价值的。预防导致谷氨酸介导的神经毒性的机制步骤可能会改善SAH引起的脑损伤并改善预后。本综述阐述了谷氨酸介导的神经毒性的当前知识，重点关注SAH后的EBI和DCI。
