TY - JOUR
T1 - Free-radical scavenger edaravone treatment confers neuroprotection against traumatic brain injury in rats
AU - Wang, Guo Hua
AU - Jiang, Zheng Lin
AU - Li, Yong Cai
AU - Li, Xia
AU - Shi, Hong
AU - Gao, Yan Qin
AU - Vosler, Peter S.
AU - Chen, Jun
PY - 2011/10/1
Y1 - 2011/10/1
N2 - 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 3mg/kg) or vehicle (normal saline) was intravenously administered at 2 and 12h 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.
AB - 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 3mg/kg) or vehicle (normal saline) was intravenously administered at 2 and 12h 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.
KW - TBI
KW - edaravone
KW - inflammatory cytokines
KW - neuroprotection
KW - oxidative stress
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U2 - 10.1089/neu.2011.1939
DO - 10.1089/neu.2011.1939
M3 - Article
C2 - 21732763
AN - SCOPUS:80054722837
SN - 0897-7151
VL - 28
SP - 2123
EP - 2134
JO - Journal of neurotrauma
JF - Journal of neurotrauma
IS - 10
ER -