{"title":"Sulbactam: A β-Lactam Compound with Neuroprotective Effects in Epilepsy.","authors":"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","doi":"10.3390/neurolint17090135","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Objectives:</b> This study investigated the impact of SUL on neuronal and behavioral changes in epilepsy by using a pentylenetetrazol (PTZ)-induced rat model of epilepsy. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"17 9","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477837/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology International","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/neurolint17090135","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.