Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks
Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks
复制标题
DOI：
10.1097/00000542-200405000-00017
复制
发表时间：
2004-05-01
期刊：
影响因子：
8.8
通讯作者：
Cechetto, DF
中科院分区：
文献类型：
--
作者：
Bayona, NA;Gelb, AW;Cechetto, DF
背景：脑卒中后立即使用异丙酚具有神经保护作用。异丙酚在神经保护中的治疗窗口期、给药时间和抗氧化机制尚不清楚。研究了异丙酚在清醒动物脑卒中后的作用。作者先前已经证明，即使在缺血发生后延迟1小时，轻异丙酚麻醉(25mg (.) kg （-1) h(-1)）持续4小时，也能减少卒中后3天的梗死面积。方法：清醒Wistar大鼠纹状体局部注射强效血管收缩剂内皮素（6 pmol / 3 μ l）诱导脑缺血。缺血后异丙酚治疗延迟至4小时，输注时间从4小时缩短至1小时。卒中后3天或21天评估梗死体积。缺血后第14-21天评估神经功能。组织抗坏血酸和谷胱甘肽浓度分别于缺血后4小时和3天测定。结果：与脂质对照组（2.4 +/- 0.7 mm(3)）相比，异丙酚治疗(25mg (.) kg(-1) （.) h(-1)）延迟2小时（0.5 +/- 0.3 mm(3)）但不延迟4小时（2.0 +/- 0.9 mm(3)），缺血后3天梗死体积减少。异丙酚输注时间为3小时而非1小时可减少梗死体积。异丙酚治疗并没有减少脑卒中后21天的梗死面积，尽管在脑卒中后14-21天观察到运动功能的改善（蒙托亚阶梯试验）。异丙酚的神经保护作用与组织抗坏血酸和谷胱甘肽浓度无关。结论：缺血后3天同时或延迟给药异丙酚对神经有保护作用。虽然缺血后21天梗死体积没有差异，但异丙酚治疗的动物在此时功能有所改善。
Background: Propofol is neuroprotective when administered immediately after stroke. The therapeutic window, duration of administration, and antioxidant mechanisms of propofol in neuroprotection are not known. The effects of propofol after stroke were examined in the conscious animal. The authors have previously shown that light propofol anesthesia (25 mg (.) kg (-1 .) h(-1)) for a period of 4 h, even if delayed 1 h after the onset of ischemia, decreases infarct volume 3 days after the stroke.Methods: Cerebral ischemia was induced in awake Wistar rats by a local intracerebral injection of the potent vasoconstrictor, endothelin (6 pmol in 3 mul) into the striatum. Propofol treatment after ischemia was delayed up to 4 h, and the infusion period shortened from 4 h to 1 h. Infarct volume was assessed 3 or 21 days after the stroke. Neurologic outcome was evaluated on days 14-21 after ischemia. Tissue ascorbate and glutathione concentrations were evaluated at 4 h and 3 days after ischemia.Results: Infarct volumes were reduced 3 days after ischemia when propofol treatment (25 mg (.) kg(-1) (.) h(-1)) was delayed for 2 h (0.5 +/- 0.3 mm(3)) but not 4 h (2.0 +/- 0.9 mm(3)), compared with intralipid controls (2.4 +/- 0.7 mm(3)). The propofol infusion period of 3 h but not 1 h reduced infarct volume. Propofol treatment did not reduce infarct volume 21 days after the stroke, although motor function improvements (Montoya staircase test) were observed 14-21 days after the stroke. Propofol neuroprotection was independent of tissue ascorbate and glutathione concentrations.Conclusions: Concurrent or delayed administration of propofol is neuroprotective 3 days after ischemia. Although there were no differences in infarct volume 21 days after ischemia, propofol-treated animals had functional improvements at this time.