title: Free-radical scavenger edaravone treatment confers neuroprotection against traumatic brain injury in rats.
abstract: Traumatic brain injury (TBI) is one of the leading causes of neurological disability in young adults. Edaravone, a novel synthetic small-molecule free-radical scavenger, has been shown to have a neuroprotective effect in both animal models of cerebral ischemia and stroke patients; however, the underlying mechanism is poorly understood. In this report, we investigated the potential mechanisms of edaravone treatment in a rat model of TBI. TBI was induced in the right cerebral cortex of male adult rats using Feeney's weight-drop method. Edaravone (0.75, 1.5, or 3 mg/kg) or vehicle (normal saline) was intravenously administered at 2 and 12 h after TBI. Edaravone treatment significantly decreased hippocampal CA3 neuron loss, reduced oxidative stress, and decreased neuronal programmed cell death compared to vehicle treatment. The protective effects of edaravone treatment were also related to the pathology of TBI on non-neuronal cells, as edaravone decreased astrocyte and glial activation. Lastly, edaravone treatment significantly reduced the presence of inflammatory cytokines, cerebral edema, blood-brain barrier (BBB) permeability, and, importantly, neurological deficits following TBI. Our results suggest that edaravone exerts a neuroprotective effect in the rat model of TBI. The likely mechanism is via inhibiting oxidative stress, leading to a decreased inflammatory response and glial activation, and thereby reducing neuronal death and improving neurological function.
authors: Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Nantong, Jiangsu, China.
authors: Guo-Hua
authors: GH
authors: Wang
authors: Zheng-Lin
authors: ZL
authors: Jiang
authors: Yong-Cai
authors: YC
authors: Li
authors: Xia
authors: X
authors: Li
authors: Hong
authors: H
authors: Shi
authors: Yan-Qin
authors: YQ
authors: Gao
authors: Peter S
authors: PS
authors: Vosler
authors: Jun
authors: J
authors: Chen
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology; D001834:Body Water / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004396:Coloring Agents; D000077553:Edaravone; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008297:Male; D017628:Microglia / Q000187:drug effects; D008854:Microscopy, Electron; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004396:Coloring Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D018696:Neuroprotective Agents; D000077553:Edaravone; D000983:Antipyrine