PDF(Pubmed)
Abstract：
Postoperative cognitive dysfunction (POCD) is a kind of serious postoperative complication in surgery with general anesthesia and it may affect patients\' normal lives. Activated microglia are thought to be one of the key factors in the regulation of POCD process. Once activated, resident microglia change their phenotype and secrete kinds of cytokines to regulate inflammatory response in tissues. Among these secretory factors, brain-derived neurotrophic factor (BDNF) is considered to be able to inhibit inflammation response and protect nervous system. Therefore, the enhancement of BDNF expression derived from resident microglia is suggested to be potential treatment for POCD. In our study, we focused on the role of C8-ceramide (a kind of interventional drug) and assessed its regulatory effect on improving the expression of BDNF secreted from microglia to treat POCD. According to the results of our study, we observed that C8-ceramide stimulated primary microglia to up-regulate the expression of BDNF mRNA after being treated with lipopolysaccharide (LPS) in vitro. We proved that C8-ceramide had ability to effectively improve POCD of mice after being accepted carotid artery exposure and their abnormal behavior recovered better than that of mice from the surgery group. Furthermore, we also demonstrated that C8-ceramide enhanced the cognitive function of mice via the PKCδ/NF-κB signaling pathway. In general, our study has confirmed a potential molecular mechanism that led to the occurrence of POCD caused by surgery and provided a new clinical strategy to treat POCD.
摘要：
术后认知功能障碍（POCD）是全麻手术中的一种严重并发症，可能影响患者的正常生活。活化的小胶质细胞被以为是POCD进程调控的症结因子之一。一旦激活,常驻小胶质细胞改变其表型并分泌多种细胞因子来调节组织炎症反应。在这些分泌因子中,脑源性神经营养因子(BDNF)被认为具有抑制炎症反应和保护神经系统的作用。因此,来自常驻小胶质细胞的BDNF表达增强被认为是POCD的潜在治疗方法。在我们的研究中,我们重点研究了C8-神经酰胺（一种干预药物）的作用，并评估了其对改善小胶质细胞分泌的BDNF表达治疗POCD的调节作用。根据我们的研究结果,我们观察到，在体外用脂多糖（LPS）处理后，C8-神经酰胺刺激原代小胶质细胞上调BDNFmRNA的表达。我们证明，C8-神经酰胺在接受颈动脉暴露后具有有效改善小鼠POCD的能力，其异常行为恢复优于手术组小鼠。此外，我们还证明C8-神经酰胺通过PKCδ/NF-κB信号通路增强小鼠的认知功能。总的来说,我们的研究证实了导致手术引起POCD发生的潜在分子机制,为POCD的治疗提供了新的临床策略.
