期刊
BRAIN RESEARCH
卷 1490, 期 -, 页码 184-192出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2012.09.011
关键词
Traumatic axonal injury; Edaravone; Free radical; Memory deficits; Amyloid precursor protein
资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology [24592133, 22791349]
- General Insurance Association of Japan
- Grants-in-Aid for Scientific Research [24592133, 22791349] Funding Source: KAKEN
Traumatic axonal injury (TAI), a feature of traumatic brain injury (TBI), progressively evolves over hours through impaired axonal transport and is thought to be a major contributor to cognitive dysfunction. In spite of various studies suggesting that pharmacologic or physiologic interventions might reduce TAI, clinical neuroprotective treatments are still unavailable. Edaravone, a free radical scavenger, has been shown to exert neuroprotective effects in animal models of several brain disorders. In this study, to evaluate whether edaravone suppresses TAI following TBI, mice were subjected to weight drop injury and had either edaravone (3.0 mg/kg) or saline administered intravenously immediately after impact. Axonal injury and oxidative stress were assessed using immunohistochemistry with antibodies against amyloid precursor protein, a marker of impaired axonal transport, and with 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage. Edaravone significantly suppressed axonal injury and oxidative stress in the cortex, corpus callosum, and hippocampus 24 h after injury. The neuroprotective effects of edaravone were observed in mice receiving 1.0, 3.0, or 10 mg/kg of edaravone immediately after impact, but not after 0.3 mg/kg of edaravone. With treatment 1 h after impact, axonal injury was also significantly suppressed and this therapeutic effect persisted up to 6 h after impact. Furthermore, behavioral tests performed 9 days after injury showed memory deficits in saline-treated traumatized mice, which were not evident in the edaravone-treated group. These results suggest that edaravone protects against memory deficits following TBI and that this protection is mediated by suppression of TAI and oxidative stress. (c) 2012 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据