A forebrain ischemic preconditioning model established in C57Black/Crj6 mice

Although many kinds of rat and gerbil cerebral ischemic preconditioning mod els are available, only a focal ischemic preconditioning model in mice has been reported. As most genetic alterations have been performed in mice, it is urgent to develop mouse ischemic preconditioning models for investigatin g the molecular mechanisms of ischemic preconditioning in transgenic mice. In the present study, we developed a forebrain ischemic preconditioning mod el in C57Black/Crj6 (C57BL/6) mice. Forebrain ischemia was induced in C57BL /6 mice (8-10 weeks old) by bilateral common carotid artery occlusion (BCCA O) for 18 min. The conditioning ischemic insult lasting for 6 min was carri ed out 48 h before the 18-min BCCAO. On the seventh day after BCCAO, neuron al damage was visualized by microtubule-associated protein-2 immunohistoche mistry and quantified by cresyl violet staining. Terminal deoxytransferase- mediated dUTP-nick end labeling (TUNEL) was performed 72 h after reperfusio n to detect DNA fragmentation. Ischemia for 18 min resulted in injury to th e striatum, cortex and hippocampus. In comparison to the hippocampus, stria tal neuronal injury was more severe and reproducible. Although the conditio ning ischemia itself caused neither noticeable striatal neuronal damage nor DNA fragmentation, it significantly reduced striatal neuronal damage and D NA fragmentation caused by the subsequent Is-min ischemia. These results in dicate that striatal neuronal injury after transient BCCAO can be strongly reduced by a sublethal ischemic episode in C57BL/6 mice. As many kinds of g ene-altered C57BL/6 mice are available, this preconditioning model may be u seful for investigating the molecular mechanisms of ischemic preconditionin g in transgenic mice. (C) 2001 Elsevier Science B.V. All rights reserved.