調節麩胺酸轉運蛋白於治療癲癇及其認知缺陷的可能效果：以頭孢曲松為例

Possible Effects of Glutamate Transporter-1 Modulation on Seizure and Cognitive Deficits: an Example of Ceftriaxone

洪菁穗(Ching-Sui Hung) ； 陳安芝(An-Chih Chen) ； 董欣(Hsin Tung) ； 王瑋翰(Wei-Han Wang) ； 何應瑞(Ying-Jui Ho)

《北市醫學雜誌》 預刊文章 Pp. 1-11

https://doi.org/10.6200/TCMJ.202101/PP.0011

摘要

癲癇主要的病理機轉涉及麩胺酸（glutamate）神經系統過度活化，以致神經受損、運動障礙與認知缺陷。過量的麩胺酸，透過N-methyl-D-aspartic acid （NMDA）受體的活化，引起神經過度興奮，增加細胞內鈣離子負荷，進而引發細胞凋亡。經由麩胺酸轉運蛋白-1（glutamate transporter-1; GLT-1），可回收清除突觸間隙的麩胺酸而降低神經之興奮性，減輕癲癇發作並產生神經保護之效果。本人及國外之研究文獻顯示促進GLT-1之表現藥物如頭孢曲松（ceftriaxone, CEF），可加速清除突觸間隙的麩胺酸，進而降低神經之興奮性，減輕癲癇發作並產生神經保護之效果。此臨床前研究顯示CEF可能具有抗癲癇及神經保護之功能，因此值得進一步推動臨床試驗，驗證CEF應用於癲癇患者的效果；以提供仍無法經由市面上的抗癲癇藥物獲得妥善控制，甚至出現神經抑制、行為鎮靜及認知障礙等副作用的30% 癲癇患者，另一可能的藥物。

關鍵字

頭孢曲松 ； 癲癇 ； 麩胺酸 ； 麩胺酸轉運蛋白 ； 神經保護

並列摘要

The primary pathologic mechanism of epilepsy is glutamate over-excitation, leading to neuronal damages, motor impairments, and cognitive deficits. Through stimulating N-methyl-D-aspartic acid (NMDA) receptors, excessive glutamates cause over-neuroexcitation and overloading of intracellular calcium and subsequent neuronal apoptosis. Glutamate transporter-1 (GLT-1) plays a role in removing excessive glutamates from the synapse cleft. Therefore, enhancing GLT-1 expression may reduce neuronal excitability, suppress seizures, and protect neurons. Approximately 30% of epileptic patients are unmanageable by conventional anti-epileptics and may even suffer from side effects of the drugs, e.g., neuronal suppression, behavioral sedation, and cognitive impairments. Ceftriaxone (CEF) can promote GLT-1 expression, accelerate the cleaning of synaptically released glutamate, thus preventing its excitotoxic action. Preclinical studies have suggested that CEF has anti-epileptic and neuroprotective efficacy. Therefore, it may be worthy to conduct clinical trials to further evaluate its effects in patients with epilepsy.

並列關鍵字

ceftriaxone ； epilepsy ； glutamate ； glutamate transporter-1 ； neuroprotection