腺苷 A1 受体激动剂在 Sturge-Weber 综合征伴耐药性癫痫患者腺苷增效治疗中的作用：一项体外电生理学研究。

The role of adenosine A1 receptor agonist in adenosine augmentation therapy for patients with refractory epilepsy in Sturge-Weber syndrome: An in vitro electrophysiological study.

机构信息

Department of Neurosurgery, Sanbo Brain Hospital Capital Medical University, Beijing, China; Brain Research Institute, Sanbo Brain Hospital Capital Medical University, Beijing, China; Beijing Key Laboratory of Epilepsy, Beijing, China.

State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, 19 Xinjiekou Wai Street, Beijing, 100875, China.

出版信息

Epilepsy Behav. 2020 May;106:107034. doi: 10.1016/j.yebeh.2020.107034. Epub 2020 Mar 21.

DOI:10.1016/j.yebeh.2020.107034

PMID:32208337

Abstract

PURPOSES

This study was to further explore the adenosine dysfunction in refractory epilepsy in Sturge-Weber Syndrome (SWS), to evaluate the neuronal-level effect of the A1 receptor (A1R) agonist on both excitatory pyramidal neurons and inhibitory interneurons, to discuss the possibility of adenosine augmentation therapy (AAT) using A1R agonist for treating refractory epilepsy in SWS.

MATERIALS AND METHODS

The intrinsic excitatory properties of pyramidal cells (PCs) and fast-spiking (FS) interneurons from human brain tissues with SWS cases and malformations of cortical development (MCD) cases were compared using electrophysiology. With application of either A1R agonist or antagonist, the neuronal-level effect of A1R agonist was evaluated in vitro in PCs and FS interneurons from SWS cases and MCD cases.

RESULTS

No significant difference of passive excitatory properties of PCs and FS interneurons was found between SWS cases and MCD cases. In terms of the neuronal-level effect of A1R agonist, with 22.88 ± 1.12% percentage of decreased frequency, FS interneurons showed relatively highest sensitivity of A1R agonist application, compared with PCs from SWS cases and FS interneurons and PCs from MCD cases.

CONCLUSION

Our results supported the potential of AATs using A1R agonist to be a novel therapy for reducing life burden from patients with refractory epilepsy in SWS, with application to epileptic generation region but not propagation region.

摘要

目的

本研究旨在进一步探讨脑颜面血管瘤病（Sturge-Weber syndrome，SWS）难治性癫痫中海马腺苷功能障碍，评估 A1 受体（A1R）激动剂对兴奋性锥体神经元和抑制性中间神经元的神经元水平效应，探讨使用 A1R 激动剂增强腺苷（adenosine augmentation therapy，AAT）治疗 SWS 难治性癫痫的可能性。

材料和方法

采用电生理学方法比较伴有 SWS 病例和皮质发育畸形（malformations of cortical development，MCD）病例的人脑组织中锥体神经元（pyramidal cells，PCs）和快速放电（fast-spiking，FS）中间神经元的固有兴奋性特性。应用 A1R 激动剂或拮抗剂，评估 A1R 激动剂在 SWS 病例和 MCD 病例的 PCs 和 FS 中间神经元中的神经元水平效应。