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Updated: Jan 11, 2026
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Cordycepin Mitigates Sepsis-Associated Encephalopathy by Promoting Microglial M2 Polarization via the
Ying Yuan1, Ganyue Fu2, Yunqiang Zhu2
1Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, NanchangUniversity, Nanchang, Jiangxi, 330006, China.
Abstract:
Sepsis-associated encephalopathy (SAE) is a serious neurological complication of systemic infection, marked by cognitive deficits, neuroinflammation, and increased mortality. Microglial activation and proinflammatory signaling pathways, particularly involving IL-17a and NF-κB, are key contributors to SAE pathogenesis. Cordycepin (3'-deoxyadenosine), a bioactive nucleoside analog from Cordyceps militaris, exhibits potent anti-inflammatory and immunomodulatory effects, yet its role in SAE remains largely unexplored. In this study, a cecal ligation and puncture (CLP) mouse model was used to evaluate the neuroprotective effects of cordycepin. Behavioral tests showed that cordycepin significantly improved cognitive performance in septic mice. 16S rRNA sequencing showed that cordycepin restored gut microbial diversity disrupted by sepsis. Immunofluorescence analysis demonstrated preserved hippocampal neuronal integrity and attenuated neuroinflammation following treatment. Mechanistically, cordycepin suppressed peripheral Th17 cell expansion, reduced IL-17a levels in both circulation and brain tissue, and downregulated IL-17RA/NF-κB signaling in hippocampal microglia. Furthermore, it promoted polarization of microglia toward the anti-inflammatory M2 phenotype. Collectively, these findings suggest that cordycepin alleviates SAE by modulating the gut-immune-brain axis, suppressing IL-17a/IL-17RA/NF-κB signaling, and enhancing microglial M2 polarization, thereby offering a promising therapeutic strategy for sepsis-related cognitive impairment.
Insights
Cordycepin, a natural compound, shows promise in treating sepsis-associated encephalopathy (SAE). It improves cognitive function, reduces brain inflammation, and restores gut health in a mouse model of sepsis.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Sepsis-associated encephalopathy (SAE) causes cognitive deficits and neuroinflammation.
- Key factors in SAE include microglial activation and IL-17a/NF-κB signaling.
- Cordycepin's effects on SAE are not well understood.
Purpose of the Study:
- To investigate the neuroprotective potential of cordycepin in a mouse model of SAE.
- To elucidate the mechanisms underlying cordycepin's effects on SAE.
Main Methods:
- Cecal ligation and puncture (CLP) model in mice.
- Behavioral tests for cognitive function.
- 16S rRNA sequencing for gut microbiota analysis.
- Immunofluorescence for neuronal integrity and neuroinflammation.
- Analysis of cytokine levels (IL-17a) and signaling pathways (IL-17RA/NF-κB).
Main Results:
- Cordycepin treatment improved cognitive performance in septic mice.
- Cordycepin restored gut microbial diversity.
- It reduced neuroinflammation, preserved hippocampal neurons, and suppressed peripheral Th17 cells.
- Cordycepin decreased IL-17a levels and inhibited IL-17RA/NF-κB signaling in microglia.
- It promoted M2 microglial polarization.
Conclusions:
- Cordycepin alleviates SAE by modulating the gut-immune-brain axis.
- It suppresses IL-17a/IL-17RA/NF-κB signaling and enhances M2 microglial polarization.
- Cordycepin represents a potential therapeutic strategy for sepsis-related cognitive impairment.
