Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke
Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke
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DOI：
10.1002/jnr.20087
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发表时间：
2004-05-15
影响因子：
4.2
通讯作者：
Singh, AK
中科院分区：
文献类型：
--
作者：
Khan, M;Sekhon, B;Singh, AK
自由基和炎症介质参与短暂性局灶性脑缺血（FCI）。n -乙酰半胱氨酸（NAC）可减轻实验性脑卒中大鼠脑缺血再灌注损伤。本研究旨在探讨NAC对实验性脑卒中缺血性事件后的神经保护作用。阻断大脑中动脉（MCA）诱导FCI 30min。NAC （150 mg/kg）在再灌注时腹腔注射，6小时后再给药。再灌注24小时后处死。脑梗死始终累及皮层和纹状体。脑梗死用2,3,5-三苯四唑氯染色。用NAC治疗的动物显示梗死面积和梗死体积显著减少，神经学评分和谷胱甘肽水平改善。即使在再灌注6小时时给予单剂量NAC，梗死的减少也是显著的。免疫组织化学和实时荧光定量PCR研究显示，与车辆处理的动物相比，NAC中促炎细胞因子如肿瘤坏死因子α (TNFalpha)、白细胞介素1 β (il -1 β)和诱导型一氧化氮合酶（NOS）的表达减少。NAC还降低了缺血脑组织中活化的巨噬细胞/小胶质细胞（ED1）的表达和凋亡细胞的死亡。这些结果表明，在实验性脑卒中大鼠模型中，即使在缺血发作后给药NAC也能保护大脑免受自由基损伤、细胞凋亡和炎症，并且治疗窗口很宽。(C) 2004 Wiley-Liss, Inc。
Free radicals and inflammatory mediators are involved in transient focal cerebral ischemia (FCI). Preadministration of N-acetylcysteine (NAC) has been found to attenuate the cerebral ischemia-reperfusion injury in a rat model of experimental stroke. This study was undertaken to investigate the neuroprotective potential of NAC administered after ischemic events in experimental stroke. FCI was induced for 30 min by occluding the middle cerebral artery (MCA). NAC (150 mg/kg) was administered intraperitoneally at the time of reperfusion followed by another dose 6 hr later. Animals were sacrificed after 24 hr of reperfusion. The cerebral infarct consistently involved the cortex and striatum. Infarction was assessed by staining the brain sections with 2,3,5-triphenyltetrazolium chloride. Animals treated with NAC showed a significant reduction in infarct area and infarct volume and an improvement in neurologic scores and glutathione level. Reduction in infarction was significant even when a single dose of NAC was administered at 6 hr of reperfusion. Immunohistochemical and quantitative real-time PCR studies demonstrated a reduction in the expression of proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) and inducible nitric oxide synthase (NOS) in NAC compared to that in vehicle-treated animals. The expression of activated macrophage/microglia (ED1) and apoptotic cell death in ischemic brain was also reduced by NAC treatment. These results indicate that in a rat model of experimental stroke, administration of NAC even after ischemia onset protected the brain from free radical injury, apoptosis, and inflammation, with a wide treatment window. (C) 2004 Wiley-Liss, Inc.