PDF(Pubmed)
Abstract：
In animal models of epilepsy, cranial surgery is often required to implant electrodes for electroencephalography (EEG) recording. However, electrode implants can lead to the activation of glial cells and interfere with physiological neuronal activity. In this study, we evaluated the impact of epidural electrode implants in the pilocarpine mouse model of temporal lobe epilepsy. Brain neuroinflammation was assessed 1 and 3 weeks after surgery by cytokines quantification, immunohistochemistry, and western blotting. Moreover, we investigated the effect of pilocarpine, administered two weeks after surgery, on mice mortality rate. The reported results indicate that implanted mice suffer from neuroinflammation, characterized by an early release of pro-inflammatory cytokines, microglia activation, and subsequent astrogliosis, which persists after three weeks. Notably, mice subjected to electrode implants displayed a higher mortality rate following pilocarpine injection 2 weeks after the surgery. Moreover, the analysis of EEGs recorded from implanted mice revealed a high number of single spikes, indicating a possible increased susceptibility to seizures. In conclusion, epidural electrode implant in mice promotes neuroinflammation that could lower the seizure thresholds to pilocarpine and increase the death rate. An improved protocol considering the persistent neuroinflammation induced by electrode implants will address refinement and reduction, two of the 3Rs principles for the ethical use of animals in scientific research.
摘要：
在癫痫动物模型中,颅脑手术通常需要植入电极以进行脑电图（EEG）记录。然而,电极植入物可导致神经胶质细胞的活化并干扰生理神经元活动。在这项研究中,我们评估了硬膜外电极植入物对毛果芸香碱颞叶癫痫小鼠模型的影响。术后1周和3周通过细胞因子定量评估脑神经炎症，免疫组织化学，和西方印迹。此外，我们研究了毛果芸香碱的作用,手术后两周给药，小鼠死亡率。报道的结果表明，植入小鼠患有神经炎症，以促炎细胞因子的早期释放为特征，小胶质细胞激活，以及随后的星形胶质增生，三周后仍然存在。值得注意的是,接受电极植入物的小鼠在手术后2周注射毛果芸香碱后显示出更高的死亡率。此外，对植入小鼠记录的脑电图的分析揭示了大量的单尖峰，表明癫痫发作的易感性可能增加。总之,在小鼠中植入硬膜外电极会促进神经炎症，从而降低毛果芸香碱的癫痫发作阈值并增加死亡率。考虑到电极植入物引起的持续性神经炎症的改进方案将解决细化和减少，在科学研究中伦理使用动物的两个3Rs原则。
