Chinese Journal of Contemporary Neurology and Neurosurgery ›› 2023, Vol. 23 ›› Issue (3): 179-188. doi: 10.3969/j.issn.1672-6731.2023.03.006

• Epilepsy and Related Disorder • Previous Articles     Next Articles

Differential effects of rapid hypothermia on pyramidal neurons and interneurons in epileptogenic tissue of epileptic patients

REN Guo-ping1, YU Tao2, XING Yue3, CHENG Li-peng4, WANG Jiao-yang3, YAN Xiao-ming2, WANG Qun1,5, ZHANG Guo-jun6, YANG Xiao-feng3   

  1. 1 Department of Epilepsy, Center of Neurology, Beijing Tiantan Hospital, Capital Medical University;China National Clinical Research Center for Neurological Diseases, Beijing 100070, China;
    2 Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
    3 Guangzhou Laboratory, Guangzhou 510006, Guangdong, China;
    4 Department of Intensive Care Unit, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100038, China;
    5 Beijing Institude for Brain Disorders, Beijing 100069, China;
    6 Department of Functional Neurosurgery, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China
  • Received:2023-02-18 Online:2023-03-25 Published:2023-04-10
  • Supported by:
    This study was supported by National Key Research and Development Program of China "Common Disease Prevention and Control Research" Key Project (No. 2022YFC2503800), the National Natural Science Foundation of China (No. 81801280), and Capital Health Research and Development of Special Project (No. 2016-1-2011).

快速低温对癫痫患者致痫灶锥体神经元和中间神经元的差异性影响

任国平1, 遇涛2, 邢悦3, 程莉鹏4, 王娇阳3, 闫晓明2, 王群1,5, 张国君6, 杨小枫3   

  1. 1 100070 首都医科大学附属北京天坛医院神经病学中心癫痫科 国家神经系统疾病临床医学研究中心;
    2 100069 北京脑重大疾病研究院;
    3 100053 北京, 首都医科大学宣武医院功能神经外科;
    4 510006 广州实验室;
    5 100038 北京中西医结合医院重症医学科;
    6 100045 首都医科大学附属北京儿童医院儿童功能神经外科
  • 通讯作者: 杨小枫,Email:xiaofengyang@yahoo.com
  • 基金资助:
    国家重点研发计划“常见多发病防治研究”重点专项(项目编号:2022YFC2503800);国家自然科学基金资助项目(项目编号:81801280);首都卫生发展科研专项(项目编号:2016-1-2011)

Abstract: Objective To explore the different effects of electrophysiological characteristics of pyramidal neurons and interneurons in epileptic patients. Methods A total of 13 brain tissue samples were selected from patients with focal drug-resistant underwent epileptogenic lesion resection in Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University from June to December 2016. Using perfusion method, the brain tissue slice temperature was quickly reduced to 20 ℃ in a step manner, then rewarmed to 30 ℃, and maintained at 30 ℃ for 10 min (the target temperature was changed by 5 ℃ every 10 min). Patch clamping technique was used to record the resting membrane potential, synaptic activity and action potential of pyramidal neurons (n = 18) and interneurons (n = 6) in epileptic cerebral cortex. Results 1) Resting membrane when the temperature dropped to 20 ℃, the resting membrane potential of the two kinds of neurons showed slight depolarization, but there was no statistical significance in the changes of resting membrane at different temperatures and the changes of resting membrane potential of the two kinds of neurons at the same temperature (P > 0.05, for all). 2) Synaptic activity: after cooling, the amplitude of excitatory postsynaptic current (EPSC) of interneuron was smaller (F = 5.332, P = 0.034). The normalized percentages of EPSC (F = 8.811, P = 0.000) and inhibitory postsynaptic current (IPSC; F = 9.843, P = 0.000) amplitude, EPSC event interval (F = 7.065, P = 0.001), EPSC (F = 6.281, P = 0.002) and IPSC (F = 8.266, P = 0.000) peak area were statistically significant. 3) Action potential: there were no significant differences in the effects of temperature change on the normalized percentages of the threshold, frequency, amplitude and half-width time of the action potential of the two kinds of neurons (P > 0.05, for all). However, the differences of normalized percentages of action potential frequency (F = 4.801, P = 0.008), amplitude (F = 3.680, P = 0.015) (F = 28.951, P = 0.000) of neuronal action potentials at different temperatures statistically significant. Conclusions When the temperature was reduced to 20 ℃, the electrophysiological activities of the two kinds of neurons were significantly inhibited. The inhibition of EPSC amplitude of synaptic activity in interneurons was stronger than that in pyramidal neurons. Inhibition of interneuron activity may be one of the reasons for hypothermia prevention and termination of epilepsy.

Key words: Epilepsy, Hypothermia, induced, Pyramidal cells, Interneurons, Electrophysiological phenomena

摘要: 目的 探讨快速低温对癫痫患者锥体神经元和中间神经元电生理学特性的影响。方法 选择2016 年6-12 月在首都医科大学宣武医院功能神经外科行手术切除的局灶性耐药性癫痫患者皮质致痫灶组织标本共13 份(13 例),经人工脑脊液灌注使其温度呈阶梯式快速降至20 ℃,随后阶梯式复温至 30 ℃并维持 10 min(每 10 min 目标温度改变 5 ℃);应用膜片钳技术记录温度变化过程中锥体神经元(18 个)和中间神经元(6 个)静息膜电位、突触活动和动作电位变化。结果 (1)静息膜电位:当温度降至20 ℃时,两种神经元静息膜电位呈轻微去极化,但不同温度以及同一温度下二者变化差异未达到统计学意义(均 P > 0.05)。(2)突触活动:随着温度降低,中间神经元兴奋性突触后电流(EPSC)波幅更小(F = 5.332,P = 0.034);且两种神经元EPSC(F = 8.811,P = 0.000)和抑制性突触后电流(IPSC;F = 9.843, P = 0.000)波幅、EPSC 事件间隔时间(F = 7.065,P = 0.001)、EPSC(F = 6.281,P = 0.002)和IPSC(F = 8.266,P = 0.000)峰面积标准化百分比差异均有统计学意义。(3)动作电位:温度变化对两种神经元动作电位阈值、频率、波幅、半宽时间标准化百分比的影响差异无统计学意义(均P > 0.05);但不同温度下神经元动作电位频率(F = 4.801,P = 0.008)、波幅(F = 3.680,P = 0.015)、半宽时间(F = 28.951,P = 0.000)标准化百分比差异具有统计学意义。结论 当温度降至20 ℃时,锥体神经元和中间神经元电生理活动被明显抑制,且对中间神经元突触活动EPSC 波幅的抑制作用更强,提示快速低温对中间神经元电活动的强抑制作用可能是其预防癫痫发生、终止癫痫发作的机制之一。

关键词: 癫痫, 低温, 人工, 锥体细胞, 中间神经元, 电生理学现象