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

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 antiepileptics 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

參考文獻

Chen CC, Chen TF, Hwang YC, et al . Population-based survey on prevalence of adult patients with epilepsy in Taiwan (Keelung community-based integrated screening no. 12). Epilepsy Res 2006; 72(1): 67-74.

Hussein AM, Ghalwash M, Magdy K, Abulseoud OA. Beta Lactams Antibiotic Ceftriaxone Modulates Seizures, Oxidative Stress and Connexin 43 Expression in Hippocampus of Pentylenetetrazole Kindled Rats. J Epilepsy Res 2016; 6(1): 8-15.

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