Increase in peripheral benzodiazepine receptors and loss of glutamate NMDA receptors in a mouse model of closed head injury: a quantitative autoradiographic study
Increase in peripheral benzodiazepine receptors and loss of glutamate NMDA receptors in a mouse model of closed head injury: a quantitative autoradiographic study
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DOI：
10.1016/j.neuroimage.2003.06.003
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发表时间：
2003-12-01
期刊：
影响因子：
5.7
通讯作者：
Biegon, A
中科院分区：
文献类型：
--
作者：
Grossman, R;Shohami, E;Biegon, A
外周型苯二氮卓类受体(PTBR)的增加已被用于检测大脑中的神经炎症和神经毒性。我们用定量放射自显影技术研究了闭合性脑损伤小鼠PTBR与NMDA受体结合密度的关系。9只小鼠体重下降诱发CHI，其中4只在伤后1小时单次注射大鼠肉瘤(RAS)抑制剂法米松硫代水杨酸盐(FTS)。假手术对照组接受麻醉，但没有挫伤。使用神经严重程度评分(NSS)在1h和7天内对小鼠的神经状态进行评估。在CHI后7天处死动物，连续切片与PTBR拮抗剂[H-3]PK11195或n-甲基-d-天冬氨酸受体(NMDAR)使用依赖性拮抗剂[H-3]MK801孵育。CHI使创伤半球的PK11195结合显著增加(两到三倍)，而NMDAR结合显著减少(20%-40%)，仅限于病变附近的区域。组织学上，这些区域以胶质细胞增殖和神经元丢失为特征。在远离病变的几个区域，包括对侧腹外侧纹状体和同侧丘脑腹侧，发现PTBR结合显著增加，但NMDAR没有随之减少。药物治疗可明显改善患者的神经功能缺失，但对PTBR的影响不大。这些结果支持在CHI的背景下胶质细胞激活和PTBR增加的复杂作用。(C)2003 Elsevier Inc.保留所有权利。
Increases in peripheral type benzodiazepine receptors (PTBR) have been utilized for the detection of neuroinflammation and neurotoxicity in the brain. We have investigated the relationship between PTBR and NMDA receptor binding density in mice with closed head injury (CHI) using quantitative autoradiography. CHI was induced by a weight drop in nine mice, four of which received a single injection of the rat sarcoma (Ras) inhibitor famesyl thiosalicylate (FTS) 1 h after the insult. Sham controls received anesthesia but no contusion. The neurological status of the mice was evaluated at 1 h, and hence up to 7 days using a neurological severity score (NSS). Animals were killed 7 days after CHI and consecutive brain sections were incubated with [H-3]PK11195, a PTBR antagonist, or [H-3]MK801, an n-methyl-d-aspartate receptor (NMDAR) use-dependent antagonist. CHI produced large (two- to threefold), widespread increases in PK11195 binding in the traumatized hemisphere and a significant decrease (20%-40%) in NMDAR binding limited to regions at close proximity to the lesion. Histologically, these regions were characterized by glial proliferation and neuronal loss. Significant increases in PTBR binding, but no concomitant decrease in NMDAR, were identified in several regions remote from the lesion, including the contralateral ventrolateral striatum and the ipsilateral ventral thalamus. Drug treatment significantly improved the neurological deficits but had only a marginal effect on PTBR. These results support a complex role for glial activation and PTBR increases in the context of CHI. (C) 2003 Elsevier Inc. All rights reserved.