Free-radical scavenger edaravone treatment confers neuroprotection against traumatic brain injury in rats

Guo Hua Wang, Zheng Lin Jiang, Yong Cai Li, Xia Li, Hong Shi, Yan Qin Gao, Peter S. Vosler, Jun Chen

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)2123-2134
Number of pages12
JournalJournal of neurotrauma
Volume28
Issue number10
DOIs
StatePublished - Oct 1 2011

Keywords

  • TBI
  • edaravone
  • inflammatory cytokines
  • neuroprotection
  • oxidative stress

ASJC Scopus subject areas

  • Clinical Neurology

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