PDF(Pubmed)
Abstract：
A lack of treatment options for temporal lobe epilepsy (TLE) demands an urgent quest for new therapies to recover neuronal damage and reduce seizures, potentially interrupting the neurotoxic cascades that fuel hyper-excitability. Endogenous opioids, along with their respective receptors, particularly dynorphin and kappa-opioid-receptor, present as attractive candidates for controlling neuronal excitability and therapeutics in epilepsy. We perform a critical review of the literature to evaluate the role of opioids in modulating microglial function and morphology in epilepsy. We find that, in accordance with anticonvulsant effects, acute opioid receptor activation has unique abilities to modulate microglial activation through toll-like 4 receptors, regulating downstream secretion of cytokines. Abnormal activation of microglia is a dominant feature of neuroinflammation, and inflammatory cytokines are found to aggravate TLE, inspiring the challenge to alter microglial activation by opioids to suppress seizures. We further evaluate how opioids can modulate microglial activation in epilepsy to enhance neuroprotection and reduce seizures. With controlled application, opioids may interrupt inflammatory cycles in epilepsy, to protect neuronal function and reduce seizures. Research on opioid-microglia interactions has important implications for epilepsy and healthcare approaches. However, preclinical research on opioid modulation of microglia supports a new therapeutic pathway for TLE.
摘要：
颞叶癫痫（TLE）缺乏治疗选择，迫切需要寻求新的治疗方法来恢复神经元损伤并减少癫痫发作。可能会中断刺激过度兴奋性的神经毒性级联反应。内源性阿片类药物，以及它们各自的受体，特别是强啡肽和κ阿片受体，作为控制癫痫神经元兴奋性和治疗的有吸引力的候选人。我们对文献进行了严格的审查，以评估阿片类药物在调节癫痫小胶质细胞功能和形态中的作用。我们发现,根据抗惊厥作用，急性阿片受体激活具有通过toll样4受体调节小胶质细胞激活的独特能力，调节细胞因子的下游分泌。小胶质细胞的异常激活是神经炎症的主要特征，发现炎性细胞因子会加重TLE，激发了通过阿片类药物改变小胶质细胞激活以抑制癫痫发作的挑战。我们进一步评估阿片类药物如何调节癫痫中的小胶质细胞激活，以增强神经保护作用并减少癫痫发作。使用受控的应用程序，阿片类药物可能会中断癫痫的炎症周期，保护神经元功能和减少癫痫发作。阿片类药物-小胶质细胞相互作用的研究对癫痫和医疗保健方法具有重要意义。然而,阿片类药物调控小胶质细胞的临床前研究支持了TLE的新治疗途径。
