舒巴坦:一种具有癫痫神经保护作用的β-内酰胺化合物。

IF 3 Q2 CLINICAL NEUROLOGY
Fang-Chia Chang, Chiung-Hui Liu, Wen-Chieh Liao, Yu-Shiuan Tzeng, Ru-Yin Tsai, Li-Ho Tseng, Ching-Sui Hung, Shey-Lin Wu, Ying-Jui Ho
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引用次数: 0

摘要

背景:癫痫的病理生理特征是由于兴奋性神经递质谷氨酸过量和抑制性神经递质γ -氨基丁酸(GABA)缺乏导致神经元活动增加。癫痫表现为癫痫发作、神经元丢失和丘脑下核(STN)过度活跃。星形胶质细胞通过谷氨酸转运蛋白-1 (glutamate transporter-1, GLT-1)吸收细胞外谷氨酸,从而减少神经元兴奋,在其中起着至关重要的作用。上调星形胶质细胞GLT-1的表达是一种很有前途的治疗癫痫的策略。舒巴坦(SUL)是一种β-内酰胺类抗生素,已被证明通过上调GLT-1的表达来发挥神经保护作用。目的:采用戊四唑(PTZ)诱导的癫痫大鼠模型,研究磺胺乙酮对癫痫神经元和行为改变的影响。方法:大鼠分别给予生理盐水、SUL(50和150 mg/kg)或SUL与GLT-1阻滞剂二氢海碱盐(DHK)联合治疗20天。随后,进行行为任务来评估认知、焦虑和记忆。结果:组织学分析显示,SUL改善了神经元缺陷,增加了星形细胞GLT-1的表达,并减少了STN的过度活跃。此外,SUL促进星形胶质细胞增殖,表明其神经保护特性的新维度。然而,DHK阻止了SUL的有益作用。结论:这项开创性的研究强调了SUL的多重益处,包括癫痫发作抑制、GLT-1表达增加和星形胶质细胞增殖,强调了其作为癫痫治疗的巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sulbactam: A β-Lactam Compound with Neuroprotective Effects in Epilepsy.

Background: The pathophysiology of epilepsy is characterized by increased neuronal activity due to an excess of the excitatory neurotransmitter glutamate and a deficiency in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Epilepsy presents with seizures, neuronal loss, and hyperactivity in the subthalamic nucleus (STN). Astrocytes play a crucial role by absorbing extracellular glutamate through glutamate transporter-1 (GLT-1), thereby reducing neuronal excitation. Upregulating the expression of astrocytic GLT-1 is a promising therapeutic strategy for epilepsy. Sulbactam (SUL), a β-lactam antibiotic, has been demonstrated to exert neuroprotective effects by upregulating GLT-1 expression. Objectives: This study investigated the impact of SUL on neuronal and behavioral changes in epilepsy by using a pentylenetetrazol (PTZ)-induced rat model of epilepsy. Methods: Rats were treated with saline, SUL (50 and 150 mg/kg), or a combination of SUL and the GLT-1 blocker dihydrokainate (DHK) for 20 days. Subsequently, behavioral tasks were conducted to assess recognition, anxiety, and memory. Results: Histological analyses revealed that SUL ameliorated neuronal deficits, increased astrocytic GLT-1 expression, and reduced hyperactivity in the STN. Additionally, SUL promoted astrocyte proliferation, indicating a new dimension of its neuroprotective properties. However, the beneficial effects of SUL were prevented by DHK. Conclusions: This pioneering study highlights multiple benefits of SUL, including seizure suppression, increased GLT-1 expression, and astrocyte proliferation, underscoring its high potential as a treatment for epilepsy.

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来源期刊
Neurology International
Neurology International CLINICAL NEUROLOGY-
CiteScore
3.70
自引率
3.30%
发文量
69
审稿时长
11 weeks
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