Lipid peroxidation is caused by reactive oxygen species (ROS) and is involved in 
traumatic brain injury (TBI). Consequently, a therapeutic strategy for TBI may 
be to control lipid peroxidation. The only drug approved to date for blocking 
lipid peroxidation is edaravone (MCI-186), a novel free-radical scavenger shown 
to exert neuroprotective effects in acute ischemic stroke. Although edaravone 
scavenges hydroxyl and nitric oxide radicals, its effect on alkoxyl radicals 
(OR-), which also contribute to lipid peroxidation, is unknown. To date, the 
study of free radicals in blood has been severely hampered by technical 
difficulties in their detection. We used an in vitro and ex vivo electron spin 
resonance (ESR) method employing 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap 
to investigate whether edaravone can scavenge OR-. By mixing either 
methemoglobin or human blood with tert-butyl hydroperoxide, we found that this 
technique can detect OR- generated in vitro. We also found that generated OR- 
can be completely absorbed by administration of edaravone in vitro (400 microM). 
Analysis of jugular venous blood collected from 17 TBI patients immediately 
before and 20 minutes after the administration of edaravone (30 mg, i.v.) 
revealed higher OR- levels in the untreated patients blood than in normal 
control blood samples. However, treatment with edaravone suppressed these OR- 
levels by 24.6% (radical intensity = 71.1 +/- 5.2-53.6 +/- 5.2; p < 0.01). Thus, 
edaravone can scavenge OR- and significantly reduce levels of these radicals in 
TBI patients. The novel ex vivo ESR method described here provides a valuable 
clinical measure of oxidative stress.