Yang Xiao-Feng, Chang Jong Hee, Rothman Steven M
Department of Neurology, Washington University School of Medicine and St. Louis Children's Hospital, One Children's Place, St. Louis, MO 63110, U.S.A.
Epilepsia. 2003 Dec;44(12):1500-5. doi: 10.1111/j.0013-9580.2003.23003.x.
Previous clinical and experimental observations have demonstrated that cooling the brain can rapidly terminate focal seizures. We wished to determine whether cooling at regular intervals could prevent or attenuate the development of seizures in a model of focal epilepsy.
We induced focal neocortical seizures in halothane-anesthetized rats by the microinjection of 4-aminopyridine (4-AP) into the motor cortex. With a small thermoelectric device, the site of the 4-AP injection was either cooled intermittently (PostCool) for 30 s every 2 min, starting 15 min after the 4-AP injection, or precooled (PreCool) for 30 min before 4-AP injection, by using the same 30-s cooling cycle. Seizures were quantified in 30-min observation periods for 1.5 h.
The average durations of PostCool and PreCool seizures were shorter than those of controls (p < 0.001). In addition, total seizure duration was significantly reduced in both groups, compared with controls (p < 0.01). The ratio of the root mean square power during a seizure to power in the immediate preseizure period was reduced in both PostCool and PreCool groups (p < 0.001). The number of seizures significantly declined over a 30- to 60-min period in both experimental groups, and by 60 min, no seizures were evident.
These experiments show that gentle cooling to 20 degrees C is capable of markedly reducing subsequent seizure frequency and intensity. The effects in our model, which generates very frequent and intense ictal activity, were robust, suggesting that prophylactic cooling might be even more beneficial in clinical situations. The physiologic mechanism for this preventive effect requires elucidation.
先前的临床和实验观察表明，冷却大脑可迅速终止局灶性癫痫发作。我们希望确定定期冷却是否能预防或减轻局灶性癫痫模型中癫痫发作的发展。
我们通过向氟烷麻醉的大鼠运动皮层微量注射4-氨基吡啶（4-AP）来诱发局灶性新皮层癫痫发作。使用小型热电装置，在4-AP注射后15分钟开始，每隔2分钟将4-AP注射部位间歇性冷却（PostCool）30秒，或在4-AP注射前30分钟进行预冷却（PreCool），采用相同的30秒冷却周期。在1.5小时的30分钟观察期内对癫痫发作进行量化。
PostCool和PreCool组癫痫发作的平均持续时间均短于对照组（p < 0.001）。此外，与对照组相比，两组的癫痫发作总持续时间均显著缩短（p < 0.01）。PostCool组和PreCool组癫痫发作期间的均方根功率与发作前即刻功率之比均降低（p < 0.001）。在30至60分钟期间，两个实验组的癫痫发作次数均显著减少，到60分钟时，无明显癫痫发作。
这些实验表明，温和冷却至20摄氏度能够显著降低随后的癫痫发作频率和强度。在我们产生非常频繁和强烈发作期活动的模型中，这种效果很显著，表明预防性冷却在临床情况下可能更有益。这种预防作用的生理机制需要阐明。
