Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat
Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat
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DOI：
10.1016/s0006-8993(02)02366-1
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发表时间：
2002-05-03
期刊：
影响因子：
2.9
通讯作者：
Uwahodo, Y
中科院分区：
文献类型：
--
作者：
Aoyama, N;Katayama, Y;Uwahodo, Y
在本研究中，我们观察了超氧阴离子自由基清除剂OPC-14117对控制性皮质撞击所致大鼠脑挫伤后继发性细胞损伤和认知功能障碍的影响。组织学检查显示，未治疗组挫伤坏死体积达13.6+/-5.3 mm(3)，OPC-14117治疗组为1.9+/-0.6 mm(3)(P<0.01)。正常对照组CA3区细胞数为120.0+/-12.4个/mm，非治疗组为73.6+/-19.9个/分，OPC-14117组为111.2+/-10.2个/mm，提示OPC-14117可减轻CCI诱导的选择性神经元死亡。用蒸汽压渗透仪测定正常脑组织渗透压为314.5+/-15.4mmo1/kg，在CCI后12h升至426.0+/-20.1mmo1/kg。组织渗透压的增加可被OPC-14117显著减轻(P<0.01)。OPC-14117给药也减轻了CCI所致的认知障碍。经OPC-14117处理的动物在Morris水迷宫测试中表现出改善的趋势。OPC-14117可显著减轻CCI引起的小鼠探索活动习惯性损伤(P<；005)。总而言之，OPC-14117可能具有减少创伤性脑损伤引起的继发性细胞损伤的潜力，因为它与在该模型中测试的任何其他化合物一样有效。(C)2002 Elsevier Science B.V.保留所有权利。
In the present study, we examined the effects of OPC-14117, a superoxide radical scavenger, on the secondary cellular damage and cognitive dysfunction occurring in a rat model of cerebral contusion induced by a controlled cortical impact (CCI). Histological examinations revealed that the contusion necrosis volume reached 13.6 +/- 5.3 mm(3) in non-treated animals and declined to 1.9 +/- 0.6 mm(3) in OPC-14117-treated animals (P < 0.01). The cell number of the CA3 region was 120.0 +/- 12.4 cells/mm in the normal controls, 73.6 +/- 19.9 cells/min in the non-treated animals, and 111.2 +/- 10.2 cells/mm in the OPC-14117-treated animals, indicating that CCI-induced selective neuronal cell death in the CA3 region was attenuated by the OPC-14117 administration (P < 0.01). The tissue osmolality, as determined with a vapor pressure osmometer, was 314.5 +/- 15.4 mmol/kg in the normal brain and increased to 426.0 +/- 20.1 mmol/kg at 12 h following CCI. The increase in tissue osmolality was significantly attenuated by OPC-14117 administration (P < 0.01). The OPC-14117 administration also attenuated the CCI-induced cognitive deficits. The OPC-14117-treated animals showed a tendency to improve on the Morris water maze performance test. The impairment of the habituation of exploratory activity elicited by CCI was significantly attenuated by OPC-14117 administration (P < 0.05). In conclusion, OPC-14117 may have a potential for decreasing secondary cellular damage due to traumatic brain injury since it is as efficacious as any other compound tested in this model. (C) 2002 Elsevier Science B.V. All rights reserved.