Chang Fang-Chia, Liu Chiung-Hui, Liao Wen-Chieh, Tzeng Yu-Shiuan, Tsai Ru-Yin, Tseng Li-Ho, Hung Ching-Sui, Wu Shey-Lin, Ho Ying-Jui
Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan.
Neurobiology and Cognitive Science Center, National Taiwan University, Taipei 10617, Taiwan.
Neurol Int. 2025 Aug 27;17(9):135. doi: 10.3390/neurolint17090135.
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. This study investigated the impact of SUL on neuronal and behavioral changes in epilepsy by using a pentylenetetrazol (PTZ)-induced rat model of epilepsy. 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. 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. 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.
癫痫的病理生理学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、神经元丧失和丘脑底核（STN）的活动亢进。星形胶质细胞通过谷氨酸转运体-1（GLT-1）吸收细胞外谷氨酸，从而减少神经元兴奋，发挥关键作用。上调星形胶质细胞GLT-1的表达是一种有前景的癫痫治疗策略。舒巴坦（SUL）是一种β-内酰胺类抗生素，已被证明可通过上调GLT-1表达发挥神经保护作用。本研究使用戊四氮（PTZ）诱导的大鼠癫痫模型，研究了SUL对癫痫中神经元和行为变化的影响。大鼠分别用生理盐水、SUL（50和150mg/kg）或SUL与GLT-1阻滞剂二氢海因酸盐（DHK）的组合治疗20天。随后，进行行为任务以评估认知、焦虑和记忆。组织学分析显示，SUL改善了神经元缺陷，增加了星形胶质细胞GLT-1的表达，并降低了STN的活动亢进。此外，SUL促进了星形胶质细胞的增殖，表明了其神经保护特性的新维度。然而，DHK阻止了SUL的有益作用。这项开创性研究突出了SUL的多种益处，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药物的巨大潜力。
