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 (3.0mg/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.