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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
C8-ceramide modulates microglia BDNF expression to alleviate postoperative cognition dysfunction via PKCδ/NF-κB
Guangqian Li1, Yuhao Wang2,3, Lei Qian1
1Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, #32 West Second Section, First-Ring Road, Chengdu, 610072, People's Republic of China.
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.
Insights
C8-ceramide enhances brain-derived neurotrophic factor (BDNF) expression in microglia, offering a potential treatment for postoperative cognitive dysfunction (POCD). This drug improved cognitive function in mice by targeting the PKCδ/NF-κB pathway.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Postoperative cognitive dysfunction (POCD) is a significant complication following general anesthesia, impacting patient recovery.
- Activated microglia and their inflammatory cytokine secretions play a key role in POCD pathogenesis.
- Brain-derived neurotrophic factor (BDNF) exhibits anti-inflammatory and neuroprotective properties, making it a target for POCD treatment.
Purpose of the Study:
- To investigate the regulatory effect of C8-ceramide on BDNF expression in microglia.
- To assess the therapeutic potential of C8-ceramide in a mouse model of POCD.
- To elucidate the molecular mechanism underlying C8-ceramide's effects on POCD.
Main Methods:
- Primary microglia were treated with lipopolysaccharide (LPS) and C8-ceramide in vitro.
- A mouse model of POCD was established using carotid artery exposure.
- Cognitive function and the PKCδ/NF-κB signaling pathway were analyzed in treated mice.
Main Results:
- C8-ceramide upregulated BDNF mRNA expression in LPS-stimulated primary microglia.
- C8-ceramide treatment significantly improved cognitive deficits in mice with POCD.
- The drug enhanced cognitive function through the PKCδ/NF-κB signaling pathway.
Conclusions:
- C8-ceramide stimulates microglia to increase BDNF expression, counteracting POCD.
- This study identifies a novel molecular mechanism involving PKCδ/NF-κB signaling in C8-ceramide's therapeutic effects.
- C8-ceramide presents a promising new clinical strategy for treating postoperative cognitive dysfunction.
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