Ren Guoping, Yan Jiaqing, Tao Guoxian, Gan Yunmeng, Li Donghong, Yan Xi, Fu Yongjuan, Wang Leiming, Wang Weimin, Zhang Zhiming, Yue Feng, Yang Xiaofeng
Neuroelectrophysiological Laboratory, Xuanwu Hospital, Capital Medical University, Beijing, China; Center of Epilepsy, Center for Brain Disorders Research, Capital Medical University, Beijing, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China.
College of Electrical and Control Engineering, North China University of Technology, Beijing, China.
Exp Neurol. 2017 Sep;295:202-210. doi: 10.1016/j.expneurol.2017.06.008. Epub 2017 Jun 7.
Rapid focal cooling is an attractive nondestructive strategy to control and possibly prevent focal seizures. However, the temperature threshold necessary to abort seizures in primates is still unknown. Here, we explored this issue in a primate epilepsy model and observed the effect of rapid cooling on different electroencephalogram frequency bands, aiming at providing necessary experimental data for future clinical translational studies and exploring the mechanism of focal cooling in terminating seizures. We induced focal neocortical seizures using microinjection of 4-aminopyridine into premotor cortex in five anesthetized cynomolgus monkeys. The rapid focal cooling was implemented by using a thermoelectric (Peltier) device. As a result, the average durations of seizures and interictal intervals before cooling were 94.3±4.0s and 62.3±6.9s, respectively. When the cortex was cooled to 20°C or 18°C, there was no effect on seizure duration (109.4±30.0s, 91.3±19.3s) or interictal duration (99.4±26.8s, 83.2±11.5s, P>0.05). But when the cortex was cooled to 16°C, the seizure duration was reduced to 54.1±4.9s and the interictal duration was extended to 175.0±16.7s (P<0.05). Electroencephalogram spectral analysis showed that the power of delta, alpha, beta, gamma and ripples bands in seizures were significantly reduced at 20°C and 18°C. At 16°C, the power of theta band in seizures was also significantly reduced along with the other bands. Our data reveal that the temperature threshold in rapid focal cooling required to significantly shorten neocortical seizures in nonhuman primates is 16°C, and inhibition of electroencephalogram broadband spectrum power, especially power of theta band, may be the underlying mechanism to control seizures.
快速局部冷却作为一种有吸引力的非破坏性策略，可用于控制甚至预防局灶性癫痫发作。然而，在灵长类动物中终止癫痫发作所需的温度阈值仍不清楚。在此，我们在灵长类癫痫模型中探讨了这一问题，并观察了快速冷却对不同脑电图频段的影响，旨在为未来的临床转化研究提供必要的实验数据，并探索局部冷却终止癫痫发作的机制。我们通过向五只麻醉的食蟹猴的运动前皮质微量注射4-氨基吡啶来诱发局灶性新皮质癫痫发作。快速局部冷却是通过使用热电（珀耳帖）装置实现的。结果，冷却前癫痫发作的平均持续时间和发作间期分别为94.3±4.0秒和62.3±6.9秒。当皮质冷却至20°C或18°C时，对癫痫发作持续时间（109.4±30.0秒，91.3±19.3秒）或发作间期持续时间（99.4±26.8秒，83.2±11.5秒，P>0.05）没有影响。但是当皮质冷却至16°C时，癫痫发作持续时间缩短至54.1±4.9秒，发作间期持续时间延长至175.0±16.7秒（P<0.05）。脑电图频谱分析表明，在20°C和18°C时，癫痫发作时δ、α、β、γ和涟漪频段的功率显著降低。在16°C时，癫痫发作时θ频段的功率与其他频段一起也显著降低。我们的数据表明，在非人灵长类动物中显著缩短新皮质癫痫发作所需的快速局部冷却温度阈值为16°C，抑制脑电图宽带频谱功率，尤其是θ频段的功率，可能是控制癫痫发作的潜在机制。
