Neuroprotective effect of edaravone in rat traumatic brain injury model - The kinetics of oxidative stress and antioxidant potency

INTRODUCTION: A large number of studies have reported that oxidative stress plays a key role in the development of TBI. Consequently, one of the keys to managing TBI may be to control lipid peroxidation. Edaravone (MCI-186), a novel free radical scavenger, was developed to prevent lipid peroxidation in neurological conditions, and is currently the only such drug approved for use on cerebral infarction patients, having been shown to improve the functional outcome as compared to placebo following ischemic stroke. Since ischemic damage contributes to the complicated pathophysiology of TBI, edaravone was also thought to have therapeutic potential in such cases. However, it has not yet been determined whether it exerts a protective effect in TBI. In the present study, we investigated the neuroprotective effect of edaravone in a rat TBI model. We also analyzed its effect on alkoxyl radicals (RO?), hydroperoxide and antioxidant potency by assaying jugular vein serum. MATERIALS AND METHODS: Animals were anesthetized with a 50 mg/kg of sodium pentobarbital. After craniectomy, a sterile metal rod 4 mm in diameter which is the device for cold injury, was chilled in liquid nitrogen, then applied to the surface of the parietal cortex for 1min. After a 10 min injury period, edaravone (3 mg/kg i.v) was administered via the right femoral artery (edaravone (+) group). Blood alkoxyl radical intensities were measured with electron spin resonance (ESR). Blood hydroperoxide levels (d-ROM) and bio antioxidant potential (BAP) were evaluated using using the free radical electron evaluator (FREE). RESULTS: The damaged area was significantly smaller in animals treated with edaravone. Jugular blood alkoxy radical intensity was suppressed 24 hours after TBI. Edaravone also suppressed serum ROM concentrations in the jugular vein at 6 and 12 hours. Serum antioxidant potency and α-tocopherol concentrations were higher in edaravone-treated animals 6 hours after TBI. CONCLUSION: In conclusion, this study provides that edaravone, a free radical scavenger, can exert neuroprotective and antiradical effects following TBI in the rat. Given that lipid peroxidation plays an important role in neurotrauma, the investigation of free radical generation, as well as determining antioxidant abilities and the effects of antioxidants including ?-tocopherol, may be important for evaluating the overall balance of oxidative stress following acute brain injury.