Bartoszek Adrian, Fornal Emilia
Department of Bioanalytics, Medical University of Lublin, Lublin, Poland.
PLoS One. 2025 Mar 4;20(3):e0317241. doi: 10.1371/journal.pone.0317241. eCollection 2025.
Epilepsy is a prevalent neurological condition marked by seizures that lead to neurobiological and behavioral impairments. Caffeine (CAF), the world's most consumed stimulant, reportedly affects both epileptic seizures and the efficacy of antiepileptic drugs, particularly topiramate (TPM). This study aimed to investigate the effects of CAF on TPM in a pentylenetetrazol (PTZ)-induced seizure model using zebrafish larvae. Four days post-fertilization Danio rerio larvae were incubated for 18 hours with CAF, TPM, or CAF+TPM, followed by an assessment of locomotor activity. Seizures were induced by adding PTZ to achieve a final concentration of 20 mM. In the PTZ-induced seizure model, the application of CAF in doses over 50 mg/L resulted in a decrease in the average movement. TPM ( > 50 μM) significantly protected larvae against the PTZ. The addition of 15 mg/L CAF to TPM did not affect larval activity at any TPM concentration tested; however, higher doses of CAF significantly reduced larval activity. CAF doses above 25 mg/L altered the activity of larvae treated with TPM in the PTZ-induced seizure model. Larvae exhibited differential heart rate (HR) responses to CAF exposure across doses. CAF at 75 mg/L significantly increased HR, while doses of 175 mg/L and higher induced bradycardia. TPM, across all tested doses, did not independently influence HR. The study provides valuable insights into the interactions between CAF and TPM, which may inform future research on human epilepsy. However, the extrapolation of these results to other species should be approached cautiously due to physiological differences.
癫痫是一种常见的神经系统疾病，其特征为发作会导致神经生物学和行为障碍。咖啡因（CAF）是全球消费最多的兴奋剂，据报道它会影响癫痫发作以及抗癫痫药物的疗效，尤其是托吡酯（TPM）。本研究旨在使用斑马鱼幼体，在戊四氮（PTZ）诱导的癫痫模型中研究CAF对TPM的影响。受精后4天的斑马鱼幼体与CAF、TPM或CAF + TPM一起孵育18小时，随后评估运动活性。通过添加PTZ使其最终浓度达到20 mM来诱导癫痫发作。在PTZ诱导的癫痫模型中，应用超过50 mg/L的CAF会导致平均运动减少。TPM（> 50 μM）能显著保护幼体免受PTZ的影响。在任何测试的TPM浓度下，向TPM中添加15 mg/L的CAF均不影响幼体活性；然而，更高剂量的CAF会显著降低幼体活性。在PTZ诱导的癫痫模型中，高于25 mg/L的CAF剂量会改变用TPM处理的幼体的活性。幼体对不同剂量的CAF暴露表现出不同的心率（HR）反应。75 mg/L的CAF会显著增加心率，而175 mg/L及更高剂量会诱导心动过缓。在所有测试剂量下，TPM均未独立影响心率。该研究为CAF与TPM之间的相互作用提供了有价值的见解，这可能为未来关于人类癫痫的研究提供参考。然而，由于生理差异，将这些结果外推至其他物种时应谨慎对待。
