Ren C, Gao X, Steinberg G K, Zhao H
Department of Neurosurgery, Stanford University School of Medicine, MSLS Building, P306, 1201 Welch Road, Room P306, Stanford, CA 94305-5327, USA.
Neuroscience. 2008 Feb 19;151(4):1099-103. doi: 10.1016/j.neuroscience.2007.11.056. Epub 2007 Dec 15.
Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 min occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 min occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for two or three cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with three cycles of 15 min performed immediately before stroke reduced infarct size from 47.7+/-7.6% of control ischemia to 9.8+/-8.6%; at two cycles of 15 min, infarct was reduced to 24.7+/-7.3%; at two cycles of 5 min, infarct was not reduced. Delayed preconditioning with three cycles of 15 min conducted 2 days before stroke also reduced infarct to 23.0+/-10.9%, but with two cycles of 15 min it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with three cycles of 15 min performed 12 h before stroke also reduced infarct to 24.7+/-4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia.
远程缺血预处理是一种新兴的中风治疗概念，但其对局灶性中风的保护作用尚未得到证实。我们测试了在同侧后肢进行的远程预处理是否能预防局灶性中风，并探索了其保护参数。通过永久性闭塞雄性大鼠左侧大脑中动脉远端（MCA）并同时闭塞双侧颈总动脉（CCA）30分钟来诱导中风。通过闭塞左后股动脉5或15分钟，随后进行相同时间的再灌注来产生肢体预处理，并重复两或三个周期。2天后测量梗死面积。结果显示，在中风前立即进行三个周期15分钟的快速预处理可使梗死面积从对照缺血的47.7±7.6%降至9.8±8.6%；两个周期15分钟时，梗死面积降至24.7±7.3%；两个周期5分钟时，梗死面积未减少。在中风前2天进行三个周期15分钟的延迟预处理也可使梗死面积降至23.0±10.9%，但两个周期15分钟时则无保护作用。远程预处理在这两个治疗时间窗的保护作用与传统预处理一致，传统预处理是在大脑自身诱导预处理缺血。出乎意料的是，在中风前12小时进行三个周期15分钟的中间预处理也可使梗死面积降至24.7±4.7%，这与传统预处理治疗时间窗的当前教条相矛盾，传统预处理在这个时间点没有保护作用。总之，在一个肢体进行的远程预处理可保护大脑局灶性缺血后的缺血损伤。
