Colbourne F, Li H, Buchan A M
Department of Pathology, Faculty of Medicine, University of Calgary, Alberta, Canada.
J Cereb Blood Flow Metab. 1999 Jul;19(7):742-9. doi: 10.1097/00004647-199907000-00003.
Considerable controversy exists about whether postischemic hypothermia can permanently salvage hippocampal CA1 neurons or just postpone injury. Studies of very brief cooling in rat have found transient benefit, whereas experiments in gerbil using protracted hypothermia report lasting protection. This discrepancy might be because of the greater efficacy of longer cooling or it might, for example, represent an important species difference. In the present study, a 48-hour period of mild hypothermia was induced starting 6 hours after 10 minutes of severe four-vessel occlusion ischemia in rats. Untreated normothermic ischemia resulted in total CA1 cell loss (99%), whereas delayed hypothermia treatment reduced neuronal loss to 14% at a 28-day survival. In unregulated rats, brain temperature spontaneously fell during ischemia, and stayed subnormal for an extended period after ischemia. This mild cooling resulted in more variable and less severe CA1 injury (75%). Finally, vertebral artery cauterization under halothane anesthesia caused an approximately 2 degrees C drop in brain temperature for 1 hour, but prevention of this hypothermia did not significantly affect CA1 damage. In summary, protracted postischemic hypothermia provided robust and long-term CA1 protection in rat. These results encourage the clinical assessment of prolonged hypothermia and its use as a model to understand ischemic CA1 injury.
关于缺血后低温是能永久性挽救海马CA1神经元还是仅仅推迟损伤，存在相当大的争议。对大鼠进行极短暂冷却的研究发现有短暂益处，而在沙鼠中使用长时间低温的实验则报告有持久保护作用。这种差异可能是由于较长时间冷却的效果更好，或者例如可能代表了一个重要的物种差异。在本研究中，在大鼠严重四动脉闭塞缺血10分钟后6小时开始诱导48小时的轻度低温。未经处理的正常体温缺血导致CA1细胞完全丧失（99%），而延迟低温治疗在28天存活时将神经元丧失减少至14%。在未调控的大鼠中，脑温在缺血期间自发下降，并在缺血后长时间保持低于正常水平。这种轻度冷却导致CA1损伤更具变异性且程度较轻（75%）。最后，在氟烷麻醉下烧灼椎动脉导致脑温下降约2摄氏度持续1小时，但防止这种低温并未显著影响CA1损伤。总之，长时间缺血后低温在大鼠中提供了强大而长期的CA1保护。这些结果鼓励对长时间低温进行临床评估，并将其用作理解缺血性CA1损伤的模型。
