Free Radical Reactions and Effects of Edaravone on Experimental Brain Injury

Introduction: This study investigates the relationship between the mechanism of traumatic brain injury and free radicals, and the influence of a novel free radical scavenger, edaravone, on experimental brain injury. Materials and Methods: Male Wistar rats were anesthetized with 1–2% halothane in a mixture of 50% oxygen and 50% air. Brain injury was produced using a controlled cortical impact injury device. Experimental rats were divided into 3 groups. In the edaravone group, edaravone (3 mg/kg) was administered twice intravenously for 30 minutes, starting at 20 minutes and then at 80 minutes after the brain injury. In the saline group, saline solution was administered in the same way as in the edaravone group. In the sham group, a burr hole was drilled without causing brain injury. This administration of edaravone or saline solution made it possible to evaluate the relative effects of edaravone by assessment of free radical reaction, lipid peroxidation, and water content. We adopted 300 MHz in vivo electron spin resonance (ESR) spectroscopy and used a spin trapping method to study free radical reactions. 3-carbamoyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (C-PROXYL) was used as the spin trapping drug. The kinetic constants (/mm) of spin clearance for C-PROXYL were used to assess the level of free radical reactions in the head. We measured the amounts of malondialdehyde (MDA), which is a by-product of lipid peroxidation. To assess brain edema, we adopted water content using the dry weight method. Results: The kinetic constants of spin clearance for C-PROXYL at several time points from 20 to 180 minutes after brain injury and the amounts of MDA in the cerebral tissue at 80, 110, and 180 minutes after brain injury were significantly higher in the saline group than in the sham group. The kinetic constants of spin clearance for CPROXYL at 50 minutes after brain injury and the amounts of MDA in the cerebral tissue at 80, 110, and 180 minutes after brain injury were significantly lower in the edaravone group than in the saline group. The water content in the injured brain at 180 minutes was significantly higher in the saline and edaravone groups than in the sham group. The water content in the injured brain at 180 minutes was significantly lower in the edaravone group than in the saline group. Conclusions: 1) Free radical reaction plays an important role in traumatic brain injury. 2) Edaravone may be effective for treatment of head injury.