Conclusions And Future Directions

Proper application of global ischemia models requires considerable attention to procedural details. Rigorous temperature control and monitoring during both intraischemic and early postischemic intervals is essential for even the most rudimentary experiment, and continuous temperature telemetry should be the requirement for a definitive intervention study. Survival times of at least 2 weeks must be the standard for evaluations of delayed hippocampal neuronal injury in such protection experiments. Electrophysiologic assessment of ischemic depolarization, although invasive and time consuming, provides a quantitative index of insult severity that identifies model inconsistencies and markedly reduces the number of animals required to draw firm conclusions. Applying current standards of monitoring and control, widely used rat and gerbil models demonstrate strikingly concordant thresholds for hippocampal neuronal damage. However, no mouse model yet meets the standards of robust injury and reproduc-ibility that have been achieved in other rodents, and further progress is needed on this front to take full advantage of genetic resources.

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