Coimbra C, Boris-Möller F, Drake M, Wieloch T
Laboratory for Experimental Brain Research, Lund University Hospital, Sweden.
Acta Neuropathol. 1996 Nov;92(5):447-53. doi: 10.1007/s004010050545.
It has been shown that changes in body core temperature several hours after a transient ischemic insult affect neuronal survival. We report that body core temperature in normal rats fluctuates over a 24-h period, while in rats subjected to 10 min transient ischemia induced by occlusion of the common carotid arteries in combination with hypotension, body temperature persistently increases to above 38.5 degrees C from 21 to 63 h following recirculation. The antipyretic drug dipyrone administered from 12 to 72 h recovery depresses body temperature to normothermic values and markedly diminishes neuronal damage in the neocortex and hippocampus when evaluated at 7 days of survival. Cooling the animals down to normothermic levels provided similar protection to that obtained with dipyrone treatment. These results suggest that hyperthermia occurring late during reperfusion aggravates delayed neuronal damage and can be effectively prevented by antipyretic drugs. The data imply that: (1) temperature-dependent processes occurring late during recovery are involved in delayed neuronal death, (2) inflammation may be an important factor in delayed neuronal death, (3) prostanoids and interleukins may contribute to this process (4) postischemic prolonged (days) temperature control is required for proper evaluation of drug therapy in brain ischemia models, and (5) fever in patients suffering brain ischemia should be impeded.
研究表明，短暂性缺血损伤数小时后，体核温度的变化会影响神经元存活。我们报告称，正常大鼠的体核温度在24小时内波动，而在通过颈总动脉闭塞联合低血压诱导10分钟短暂性缺血的大鼠中，再灌注后21至63小时体温持续升高至38.5摄氏度以上。在恢复后12至72小时给予解热药物安乃近可将体温降至正常体温水平，并在存活7天时评估时显著减少新皮层和海马体中的神经元损伤。将动物体温降至正常体温水平可提供与安乃近治疗相似的保护。这些结果表明，再灌注后期出现的体温过高会加重迟发性神经元损伤，解热药物可有效预防。数据表明：（1）恢复后期发生的温度依赖性过程与迟发性神经元死亡有关；（2）炎症可能是迟发性神经元死亡的重要因素；（3）前列腺素和白细胞介素可能促成这一过程；（4）在脑缺血模型中，为正确评估药物治疗，需要对缺血后延长（数天）的体温进行控制；（5）脑缺血患者的发热应得到抑制。
