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Figure 1: Establishment of TBI model and experimental protocol. (a) Brain images following TBI. The contusion was conducted over the right parietotemporal cortex 2.0 mm caudal of bregma and 3.0 mm lateral of the midline. (b) High power images of the CCI device showing a rounded tip of approximately 1.2 mm in diameter. (c) Coronal cryosections (thickness 50 μm) from bregma to approximately 3.9 mm caudal of bregma encompassing the injury region were used to determine the injury area. The core-injury area was defined as the direct impact region 1.2 mm to 2.4 mm caudal of bregma. The peri-injury area was defined as being <1.2 mm and >2.4 mm caudal of bregma. (d) The free radical scavenger edaravone was injected intravenously into the jugular vein following CCI. To determine the possible therapeutic time window, edaravone (3.0 mg/kg, for each time point) was administered either immediately (0) or 3 or 6 hours following CCI. As a vehicle-treated control group, saline was administered immediately (0 hour) following CCI ( ). (e) Temporal profiles of ROS, oxidative stress, and neuronal death in the brain following CCI were determined immediately (0) and at 3, 6 and 24 hours after CCI ( ). (f) Edaravone treatment to ROS was investigated. Edaravone was administered to group 1: immediately (0 hour) or group 2: 3 hours after the CCI and in situ detection of were performed 4 hours post-CCI. As the control, Group 3: vehicle was administered 3 hours post-CCI and in situ detection of was also performed 4 hours following CCI.