Edaravone ameliorates oxidative stress associated cholinergic dysfunction and limits apoptotic response following focal cerebral ischemia in rat
Edaravone ameliorates oxidative stress associated cholinergic dysfunction and limits apoptotic response following focal cerebral ischemia in rat
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DOI：
10.1007/s11010-012-1335-6
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发表时间：
2012-08-01
影响因子：
4.3
通讯作者：
Islam, Fakhrul
中科院分区：
文献类型：
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作者：
Ahmad, Ajmal;Khan, Mohd. Moshahid;Islam, Fakhrul
脑卒中是一种危及生命的疾病，是世界范围内死亡和发病的主要原因。脑缺血后的神经元损伤是脑卒中患者的严重危险因素。氧化应激和凋亡损伤在脑缺血发病机制中起重要作用，并可能成为治疗的靶点。本研究的目的是验证依达拉奉（Edv）给药可维持大鼠脑内抗氧化状态，改善胆碱能功能障碍并抑制凋亡反应进展的假设。为了验证这一假设，雄性Wistar大鼠进行大脑中动脉闭塞（MCAO）2小时，然后再灌注22小时。在缺血发作前30分钟和再灌注后1小时，腹腔注射Edv（10 mg/kg bwt）。再灌注后，检测大鼠的神经行为活动，并处死大鼠，测量梗死体积，估计氧化损伤标志物。Edv治疗显著减少缺血性病变体积，改善神经功能缺损，对抗氧化负荷，并抑制凋亡损伤。总之，Edv治疗改善了MCA闭塞大鼠的神经和组织学结局，提高了内源性抗氧化剂状态，并减少了对细胞凋亡反应的诱导。我们推测Edv是减少自由基及其相关胆碱能功能障碍和凋亡损伤的药理学药物之一，并且已发现其限制中风后脑损伤的程度。
Stroke is a life-threatening disease with major cause of mortality and morbidity worldwide. The neuronal damage following cerebral ischemia is a serious risk to stroke patients. Oxidative stress and apoptotic damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The objective of this study was to test the hypothesis that administration of edaravone (Edv) maintains antioxidant status in brain, improves the cholinergic dysfunction and suppresses the progression of apoptosis response in rat. To test this hypothesis, male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) of 2 h followed by reperfusion for 22 h. Edv was administered (10 mg/kg bwt) intraperitoneally 30 min before the onset of ischemia and 1 h after reperfusion. After reperfusion, rats were tested for neurobehavioral activities and were sacrificed for the infarct volume, estimation of oxidative damage markers. Edv treatment significantly reduced ischemic lesion volume, improved neurological deficits, contended oxidative loads, and suppressed apoptotic damage. In conclusion, treatment with Edv ameliorated the neurological and histological outcomes with elevated endogenous anti-oxidants status as well as reduced induction of apoptotic responses in MCA occluded rat. We theorized that Edv is among the pharmacological agents that reduce free radicals and its associated cholinergic dysfunction and apoptotic damage and have been found to limit the extent of brain damage following stroke.