Hoyte Lisa C, Papadakis Michalis, Barber Philip A, Buchan Alastair M
Calgary Stroke Program, Hotchkiss Brain Institute, University of Calgary, Canada.
Brain Res. 2006 Nov 22;1121(1):231-7. doi: 10.1016/j.brainres.2006.08.107. Epub 2006 Sep 29.
Ischemic preconditioning (IPC) induces protection to cerebral ischemia. However, it was previously unclear whether this protection resulted from altered susceptibility to ischemia. The current study examines the effects of late phase ischemic preconditioning in a mouse model of middle cerebral artery occlusion (MCAO). Specific examination of the regional cerebral blood flow (rCBF) was conducted.
Intra-abdominal radiofrequency probes were implanted in animals and core temperature was regulated. Mice were subjected to MCAO: (1) brief 15 min duration (preconditioning ischemia) and (2) 45 min MCAO (injurious ischemia). Naive (i.e. not preconditioned) animals were compared with preconditioned animals (preconditioning ischemia plus injurious ischemia at 72 h reperfusion). rCBF was measured using laser Doppler flowmetry (LDF) and magnetic resonance cerebral perfusion (MRP) arterial spin labeling. Percentage of brain infarcted was compared between groups.
rCBF was significantly improved in the preconditioned cohorts of mice. Naive animals showed flow reductions to 16+/-3.59% (MCAO_45; injurious, unpreconditioned) and 17.1+/-8.6% (MCAO_15; preconditioning ischemia alone) of baseline, while preconditioned animals had flows 33.9+/-13.2% (IPC_45; preconditioned animals with injurious ischemia at 72 h reperfusion) of baseline (p=0.001). Percentage of brain infarcted was 17.2+/-6.2% in naive animals, while it was 5.1+/-4.6% in the preconditioned animals (p=0.003). MRP of the perfusion to the ischemic hemisphere, in a striatal coronal slice of the brain was 26.7+/-5.8% of the contralateral hemisphere in naive animals while preconditioned mice had flows of 38.7+/-6.8% of contralateral (p=0.04).
Improved rCBF is an important factor in the protection of IPC, during injurious MCAO in the mouse. Stringent monitoring of rCBF is required in future studies of IPC.
缺血预处理（IPC）可诱导对脑缺血的保护作用。然而，此前尚不清楚这种保护作用是否源于对缺血易感性的改变。本研究在大脑中动脉闭塞（MCAO）小鼠模型中考察了晚期缺血预处理的作用。对局部脑血流量（rCBF）进行了具体检测。
在动物体内植入腹腔射频探头并调节核心体温。小鼠接受MCAO：（1）持续15分钟的短暂缺血（预处理缺血）和（2）45分钟的MCAO（损伤性缺血）。将未进行预处理的动物（即未预处理组）与预处理动物（预处理缺血加72小时再灌注时的损伤性缺血）进行比较。使用激光多普勒血流仪（LDF）和磁共振脑灌注（MRP）动脉自旋标记法测量rCBF。比较两组之间脑梗死的百分比。
预处理组小鼠的rCBF显著改善。未预处理动物的血流量降至基线的16±3.59%（MCAO_45；损伤性，未预处理）和17.1±8.6%（MCAO_15；仅预处理缺血），而预处理动物的血流量为基线的33.9±13.2%（IPC_45；72小时再灌注时接受损伤性缺血的预处理动物）（p = 0.001）。未预处理动物的脑梗死百分比为17.2±6.2%，而预处理动物为5.1±4.6%（p = 0.003）。在大脑纹状体冠状切片中，未预处理动物缺血半球的灌注MRP为对侧半球的26.7±5.8%，而预处理小鼠的血流量为对侧的38.7±6.8%（p = 0.04）。
在小鼠损伤性MCAO期间，rCBF的改善是IPC保护作用的一个重要因素。在未来的IPC研究中需要严格监测rCBF。
