Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage
Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage
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DOI：
10.1161/strokeaha.107.486654
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发表时间：
2008-02-01
期刊：
影响因子：
8.3
通讯作者：
Itano, Toshifumi
中科院分区：
文献类型：
--
作者：
Nakamura, Takehiro;Kuroda, Yasuhiro;Itano, Toshifumi
背景和目的-我们以前的研究已经证明脑出血（ICH）后大脑中发生氧化性DNA损伤。因此，我们研究是否依达拉奉，自由基清除剂，可以减少ICH-诱导的brain injury.Methods -这些实验使用戊巴比妥麻醉，雄性Sprague-Dawley大鼠接受了100 μ L自体全血（ICH），FeCl 2，或凝血酶到右基底神经节的输液。24小时后，这些老鼠被人道地杀死。共有4组实验。首先，通过测量脑水肿和神经功能缺损检查依达拉奉对ICH诱导的脑损伤的剂量依赖性作用。在第二组中，在ICH治疗后研究了脱嘌呤/脱嘧啶脱碱基位点和8-羟基-2 '-脱氧鸟苷，它们是DNA氧化的标志。在第三，延迟治疗依达拉奉对ICH诱导的损伤的效果进行了测定，而第四检查依达拉奉对铁和凝血酶诱导的brain injury.Results的影响依达拉奉系统给药后立即或2小时ICH减少脑含水量24小时后，与车辆（P < 0.05）。依达拉奉治疗后即刻或2 h也能改善神经功能缺损（P < 0.05）。依达拉奉还减弱ICH诱导的脱嘌呤/脱嘧啶脱碱基位点和8-羟基-2 '-脱氧鸟苷的变化，并减少铁和凝血酶诱导的脑损伤。它还可以减少铁和凝血酶引起的脑损伤。这些结果表明依达拉奉是一种潜在的治疗ICH的药物。
Background and Purpose - Our previous studies have demonstrated that oxidative DNA injury occurs in the brain after intracerebral hemorrhage (ICH). We therefore examined whether edaravone, a free-radical scavenger, could reduce ICH-induced brain injury.Methods - These experiments used pentobarbital-anesthetized, male Sprague-Dawley rats that received an infusion of either 100 mu L autologous whole blood (ICH), FeCl2, or thrombin into the right basal ganglia. The rats were humanely killed 24 hours later. There were 4 sets of experiments. In the first, the dose-dependent effects of edaravone on ICH-induced brain injury were examined by measuring brain edema and neurologic deficits. In the second set, apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine, which are hallmarks of DNA oxidation, were investigated after treatment for ICH. In the third, the effect of delayed treatment with edaravone on ICH-induced injury was determined, whereas the fourth examined the effects of edaravone on iron- and thrombin-induced brain injury.Results - Systemic administration of edaravone immediately or 2 hours after ICH reduced brain water content 24 hours after ICH compared with vehicle (P < 0.05). Edaravone treatment immediately or 2 hours after ICH also ameliorated neurologic deficits (P < 0.05). Edaravone also attenuated ICH-induced changes in apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine and reduced iron- and thrombin-induced brain injury.Conclusions - Edaravone attenuates ICH-induced brain edema, neurologic deficits, and oxidative injury. It also reduces iron- and thrombin-induced brain injury. These results suggest that edaravone is a potential therapeutic agent for ICH.