• Manabu Ohta, Youichirou Higashi, Toshio Yawata, Masahiro Kitahara, Atsuya Nobumoto, Eri Ishida, Masayuki Tsuda, Yasunori Fujimoto, and Keiji Shimizu.
• Department of Neurosurgery, Kochi Medical School, Kohasu, Okoh-cho, Nankoku, Kochi 783-8505, Japan. b08d6b05@s.kochi-u.ac.jp
• Brain Res. 2013 Jan 15;1490:184-92.

AbstractTraumatic 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 (3.0mg/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 24h after injury. The neuroprotective effects of edaravone were observed in mice receiving 1.0, 3.0, or 10mg/kg of edaravone immediately after impact, but not after 0.3mg/kg of edaravone. With treatment 1h after impact, axonal injury was also significantly suppressed and this therapeutic effect persisted up to 6h 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.Copyright © 2012 Elsevier B.V. All rights reserved.

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