Lee Vanessa Lin Lin, Norazit Anwar, Noor Suzita Mohd, Shaikh Mohd Farooq
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor, Malaysia.
Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Front Pharmacol. 2022 Apr 4;13:821618. doi: 10.3389/fphar.2022.821618. eCollection 2022.
Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Mounting evidence suggests the link between epileptogenesis and neuroinflammation. We hypothesize that eliminating neuroinflammation can alleviate seizure severity and prolong seizure onset. (CS) is a snakehead murrel commonly consumed by locals in Malaysia, believed to promote wound healing and mitigate inflammation. This study aims to unravel the anticonvulsive potential of CS extract on neuroinflammation-induced seizures using an adult zebrafish model. Neuroinflammation was induced cerebroventricular microinjection of lipopolysaccharides from and later challenged with a second-hit pentylenetetrazol at a subconvulsive dose of 80 mg/kg. Zebrafish behaviour and swimming pattern analysis, as well as gene expression analysis, were done to study the pharmacological property of CS. CS extract pre-treatment in all doses significantly reduced seizure score, prolonged seizure onset time and slightly improved the locomotor swimming pattern of the zebrafish. CS extract pre-treatment at all doses significantly reduced the expression of NFB gene in the brain, and CS extract at 25 mg/L significantly reduced the IL-1 gene expression suggesting anti-neuroinflammatory properties. However, there were no significant changes in the TNFα. Besides, CS extract at 50 mg/L also elevated the expression of the CREB gene, which exerts neuroprotective effects on the neurons and the NPY gene, which plays a role in modulating the inhibition of the excitatory neurotransmission. To sum up, CS extract demonstrated some anticonvulsive and anti-inflammatory activity on neuroinflammation-induced seizures. Still, more studies need to be done to elucidate the mechanism of action of CS extract.
癫痫是一种以反复发作的无诱因癫痫发作为特征的神经系统疾病。越来越多的证据表明癫痫发生与神经炎症之间存在联系。我们假设消除神经炎症可以减轻癫痫发作的严重程度并延长癫痫发作的起始时间。(CS)是马来西亚当地人常食用的一种乌鳢,据信具有促进伤口愈合和减轻炎症的作用。本研究旨在使用成年斑马鱼模型揭示CS提取物对神经炎症诱导的癫痫发作的抗惊厥潜力。通过脑室内微量注射脂多糖诱导神经炎症,随后以80mg/kg的亚惊厥剂量用第二次打击戊四氮进行挑战。进行斑马鱼行为和游泳模式分析以及基因表达分析以研究CS的药理特性。所有剂量的CS提取物预处理均显著降低癫痫发作评分,延长癫痫发作起始时间,并略微改善斑马鱼的运动游泳模式。所有剂量的CS提取物预处理均显著降低大脑中NFB基因的表达,25mg/L的CS提取物显著降低IL-1基因表达,表明具有抗神经炎症特性。然而,TNFα没有显著变化。此外,50mg/L的CS提取物还提高了对神经元具有神经保护作用的CREB基因和在调节兴奋性神经传递抑制中起作用的NPY基因的表达。综上所述,CS提取物对神经炎症诱导的癫痫发作表现出一定的抗惊厥和抗炎活性。然而,仍需要更多的研究来阐明CS提取物的作用机制。