Inhibition of the cerebral ischemic injury by ethyl pyruvate with a wide therapeutic window
Inhibition of the cerebral ischemic injury by ethyl pyruvate with a wide therapeutic window
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DOI：
10.1161/01.str.0000181779.83472.35
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发表时间：
2005-10-01
期刊：
影响因子：
8.3
通讯作者：
Lee, JK
中科院分区：
文献类型：
--
作者：
Yu, YM;Kim, JB;Lee, JK
背景和目的-丙酮酸乙酯（EP）是一种丙酮酸衍生物，最近有报道称其可预防已建立致死性脓毒症和全身炎症的小鼠的致死性。在这项研究中，我们研究了EP在大鼠大脑中动脉闭塞（MCAO）的脑缺血模型中的神经保护作用。方法-雄性Sprague-Dawley大鼠进行1小时的MCAO，并在MCAO之前或之后的不同时间点给予EP。评价脑梗死、神经功能缺损、小胶质细胞活化和促炎细胞因子表达的变化。BV 2小胶质细胞也被用来评估EP的抗炎作用。结果-在MCAO前30分钟或在MCAO后4小时或12小时腹腔内给予EP使梗塞体积减少至10.3 +/- 3.4%。（n=6; P < 0.05）、21.5 ± 2.7%（n =6; P < 0.05）和44.3 ± 4.0%（n =6; P < 0.05）。梗死体积的显著减少伴随着与脑缺血相关的临床表现的抑制，包括运动障碍和神经功能缺损、小胶质细胞活化和促炎细胞因子表达。当在MCAO/再灌注后24小时给予EP时，其神经保护作用仍然明显（76.5 ± 4.70%; n=; P < 0.05）。EP抑制脂多糖诱导的激活BV 2 cells，证明了减少NO的释放和伴随的诱导的促炎cytokines.Conclusions -这些结果表明，EP提供了强有力的保护迟发性脑缺血性损伤具有广泛的治疗窗口。
Background and Purpose - Ethyl pyruvate (EP) is a pyruvate derivative that has been reported recently to prevent lethality in mice with established lethal sepsis and systemic inflammation. In this study, we examined the neuroprotective effect of EP in a rat cerebral ischemia model of middle cerebral artery occlusion (MCAO).Methods - Male Sprague-Dawley rats were subjected to 1 hour of MCAO, and EP was administered at various time points before or after MCAO. The changes in the brain infarction, neurological deficits, microglia activation, and proinflammatory cytokine expression were evaluated. BV2 microglial cells were also used to access the anti-inflammatory effect of EP.Results - The administration of EP intraperitoneally at 30 minutes before or at 4 or 12 hours after MCAO reduced the infarct volume to 10.3 +/- 3.4% (n=6; P < 0.05), 21.5 +/- 2.7% ( n =6; P < 0.05), and 44.3 +/- 4.0% (n =6; P < 0.05), respectively, of that of the control group. The significant reduction in infarct volume was accompanied by the suppression of the clinical manifestations associated with cerebral ischemia, including motor impairment and neurological deficits, microglial activation, and proinflammatory cytokine expression. The neuroprotective effect of EP was yet evident when it was administered as late as 24 hours after MCAO/ reperfusion (76.5 +/- 4.70%; n=; P < 0.05). EP suppressed lipopolysaccharide induced activation of BV2 cells, as was evidenced by a reduction in NO release and the accompanying induction of proinflammatory cytokines.Conclusions - These results suggest that EP affords the strong protection of the delayed cerebral ischemic injury with a wide therapeutic window.