Resolvin D1 protects against sepsis-associated encephalopathy in mice by inhibiting neuro-inflammation induced by microglia
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Updated: Aug 25, 2025
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Bing Xu1, Mi Li2, Tingting Cheng3
1Department of Anesthesiology, Changhai Hospital, Naval Medical University Shanghai 200433, China.
Objectives:
Neuro-inflammation induced by microglia is crucial in the pathogenesis of sepsis-associated encephalopathy (SAE). The endogenous lipid mediator, Resolvin D1 (RvD1), which is synthesized from docosahexaenoic acid, has been extensively reported to attenuate inflammation in various diseases by its anti-inflammation and pro-resolving functions. However, the effect of RvD1 on SAE remains unclear. In this study, we aimed to ex the function and mechanism of RvD1 on SAE mice.
Methods:
In our study, the SAE mice model was established by the method of cecal ligation and perforation (CLP). C57BL/6J mice were randomly divided into three groups: the Sham group, the CLP group and the CLP+RvD1 group. Cognitive impairment of the mice was assessed by Morris water maze. Iba1 immunohistochemistry was conducted to observe the activation of microglia in hippocampus of the mice from different groups. The production of cytokines, including TNF-α, IL-6 and IL-1β, and their mRNA levels were evaluated by ELISA and Q-PCR. The expression of the molecules from inflammatory signaling pathways was assessed by Western blot.
Results:
xaRvD1 treatment significantly improved the learning and cognitive ability of SAE mice. The activation of microglia and the production of inflammatory cytokines in hippocampal tissues were inhibited in CLP+RvD1 group. We also found that the inflammation of microglia was attenuated by RvD1 treatment both in vivo and in vitro. Moreover, the activation of NF-κB, MAPK and STAT signaling pathways were inhibited by RvD1 treatment, which partly explained the anti-inflammation function of RvD1 on SAE mice.
Conclusions:
RvD1 could improve the learning and cognitive ability of SAE mice by inhibiting the systemic and local inflammation. It could attenuate the inflammation in microglia by inhibiting the activation of inflammatory signaling pathways and then decreasing the production of cytokines. These findings are helpful to better understand the pathophysiology of SAE, which also provide a novel therapeutic method in clinic.
Insights
Resolvin D1 (RvD1) treatment improved cognitive function in sepsis-associated encephalopathy (SAE) mice by reducing neuroinflammation. RvD1 inhibited microglial activation and inflammatory pathways, offering a potential therapeutic strategy for SAE.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Sepsis-associated encephalopathy (SAE) involves crucial neuroinflammation mediated by microglia.
- Resolvin D1 (RvD1), a lipid mediator from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties.
- The therapeutic potential of RvD1 in SAE remains largely unexplored.
Purpose of the Study:
- To investigate the functional role and underlying mechanisms of RvD1 in a mouse model of SAE.
- To evaluate RvD1's efficacy in mitigating cognitive deficits and neuroinflammation associated with SAE.
Main Methods:
- A cecal ligation and perforation (CLP) model was used to induce SAE in C57BL/6J mice.
- Cognitive function was assessed using the Morris water maze.
- Microglial activation, cytokine production (TNF-α, IL-6, IL-1β), and inflammatory signaling pathways (NF-κB, MAPK, STAT) were analyzed.
Main Results:
- RvD1 treatment significantly ameliorated learning and cognitive impairments in SAE mice.
- RvD1 administration reduced microglial activation and pro-inflammatory cytokine levels in hippocampal tissues.
- RvD1 inhibited the activation of NF-κB, MAPK, and STAT signaling pathways, demonstrating its anti-inflammatory effects both *in vivo* and *in vitro*.
Conclusions:
- RvD1 effectively improves cognitive function in SAE mice by suppressing systemic and local neuroinflammation.
- RvD1 attenuates microglial inflammation by inhibiting key inflammatory signaling pathways and cytokine production.
- These findings highlight RvD1 as a promising therapeutic agent for SAE, offering insights into its pathophysiology.
