Combination drug therapy and mild hypothermia after transient focal cerebral ischemia in rats
Combination drug therapy and mild hypothermia after transient focal cerebral ischemia in rats
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DOI：
10.1161/01.str.0000083622.65684.21
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发表时间：
2003-09-01
期刊：
影响因子：
8.3
通讯作者：
Schmid-Elsaesser, R
中科院分区：
文献类型：
--
作者：
Zausinger, S;Schöller, K;Schmid-Elsaesser, R
背景和目的--我们最近证实，在局灶性短暂性脑缺血大鼠模型中，镁（钙和谷氨酸拮抗剂）和替拉扎德（抗氧化剂）预处理联合缺血内亚低温（33 ℃）（MTH）可提供上级神经保护作用。在本研究中，我们调查了这个治疗策略的时间窗与posttreatment方案，以确定其作用为中风patients. Methods，我们进行了48 Sprague-Dawley大鼠90分钟的大脑中动脉闭塞的管腔内细丝。激光多普勒血流仪连续记录双侧局部脑血流。在诱导缺血后0、1、3和5小时开始与MTH的联合治疗。每隔1小时给药一次，维持低温2小时。每天评估神经功能缺损。术后第7天通过平面测量法测定脑梗死面积。结果：与常温对照组相比，在诱导缺血后0、1和3小时联合应用MTH治疗可显著减少梗死体积，分别为-74%、-49%和-45%。此外，这些治疗组在缺血后第1天和第2天表现出更少的神经功能缺损（P
Background and Purpose-We have recently demonstrated that pretreatment with magnesium (calcium and glutamate antagonist) and tirilazad ( antioxidant) in combination with intraischemic mild hypothermia (33degreesC) (MTH) offers superior neuroprotective efficacy in a rat model of focal transient cerebral ischemia. In the present study, we investigated the time window of this treatment strategy with a posttreatment regimen to define its role for stroke patients.Methods-We subjected 48 Sprague-Dawley rats to 90 minutes of middle cerebral artery occlusion by an intraluminal filament. Bilateral regional cerebral blood flow was continuously recorded by laser Doppler flowmetry. Combination therapy with MTH was started at 0, 1, 3, and 5 hours after induction of ischemia. Drugs were given in 1-hour intervals, and hypothermia was maintained for 2 hours. Neurological deficits were assessed daily. Infarct size was planimetrically determined on postoperative day 7.Results-Combination therapy with MTH significantly reduced infarct volume compared with normothermic controls by -74%, -49%, and -45% when applied at 0, 1, and 3 hours after induction of ischemia. Furthermore, these treatment groups showed less neurological deficits on postischemic days 1 and 2 (P