Effects of in situ administration of excitatory amino acid antagonists on rapid microglial and astroglial reactions in rat hippocampus following traumatic brain injury
Effects of in situ administration of excitatory amino acid antagonists on rapid microglial and astroglial reactions in rat hippocampus following traumatic brain injury
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DOI：
10.1179/016164107x251745
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发表时间：
2008-05-01
影响因子：
1.9
通讯作者：
Katayama, Yoichi
中科院分区：
文献类型：
--
作者：
Suma, Takeshi;Koshinaga, Morimichi;Katayama, Yoichi
目的：小胶质细胞和星形胶质细胞对创伤性脑损伤（TBI）均有即时反应。本研究旨在探讨兴奋性氨基酸（EAA）拮抗剂是否能减弱这种神经胶质反应。EAA拮抗剂，包括广谱EAA拮抗剂犬尿烯酸（KYN）、特异性N-甲基-D-天冬氨酸（NMDA）受体阻断剂2-氨基-5-膦酰基戊酸（AP-5）和AMPA-KA受体阻断剂6，7-二硝基喹喔啉-2，3-二酮（DNQX），以及电压依赖性离子通道阻断剂河豚毒素（TTX），通过透析探针注入大鼠单侧海马30分钟，然后诱导单侧控制性皮质撞击损伤。损伤后10分钟处死大鼠，并对它们的脑进行化学处理以检测OX 42（小胶质细胞的标记物）和胶质细胞酸性蛋白（GFAP;星形胶质细胞的标记物）。目的：损伤后10分钟，在整个半球（包括损伤侧的海马）中，具有增加的OX 42免疫反应性的小胶质细胞活化是明显的。同样，肿胀的星形胶质细胞与GFAP表达增加，可以检测到专门的损伤侧。当KYN在损伤前原位给药时，海马中的快速小胶质细胞和星形胶质细胞反应均显著减弱。然而，AP-5，DNQX和TTX，电压依赖性离子通道阻滞剂，在剂量，可以抑制每个通道激活，未能减弱这些神经胶质reactions.Discussion：这些研究结果表明，大量的离子通量和/或伴随发生的EAA释放可能是密切相关的小胶质细胞和星形胶质细胞的反应TBI后的启动。
Objective: Both microglia and astrocytes respond immediately to traumatic brain injury (TBI). The present study was undertaken to examine whether or not excitatory amino acid (EAA) antagonists could attenuate such glial responses.Methods: EAA antagonists, including the broad spectrum EAA antagonist, kynurenic acid (KYN), specific N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovalerate (AP-5), and AMPA-KA receptor blocker, 6,7-dinitroquinoxaline-2,3-dione (DNQX), as well as the voltage-dependent ion channel blocker, tetrodotoxin (TTX), were administered into the unilateral hippocampus of rats through a dialysis probe for 30 minutes before the induction of unilateral controlled cortical impact injury. The rats were killed 10 minutes after injury and their brains were processed immunohistochemically for OX42 (marker for microglia) and glial fibrillary acidic protein (GFAP; marker for astrocytes).Objective: Ten minutes after injury, microglial activation with increased OX42 immunoreactivity was evident in the entire hemisphere including the hippocampus ipsilateral to the injury side. Similarly, swollen astrocytes with increased GFAP expression could be detected exclusively on the injury side. When KYN was administered in situ before injury, both the rapid microglial and astroglial responses in the hippocampus were significantly attenuated. However, AP-5, DNQX and TTX, the voltage-dependent ion channel blocker, at doses which can inhibit each channel activation, failed to attenuate these glial reactions.Discussion: These findings indicate that massive ionic fluxes and/or concomitantly occurring EAA release may be closely related to the initiation of microglial and astroglial responses following TBI.