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Sodium butyrate attenuates microglia-mediated neuroinflammation by modulating the TLR4/MyD88/NF-κB pathway and microbiome-gut-brain axis in cardiac arrest mice.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101468876 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-6606 (Electronic) Linking ISSN: 17566606 NLM ISO Abbreviation: Mol Brain Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central
    • Subject Terms:
      Myeloid Differentiation Factor 88*/metabolism ; Toll-Like Receptor 4*/metabolism ; Microglia*/drug effects ; Microglia*/metabolism ; Microglia*/pathology ; NF-kappa B*/metabolism ; Butyric Acid*/pharmacology ; Butyric Acid*/therapeutic use ; Gastrointestinal Microbiome*/drug effects ; Signal Transduction*/drug effects ; Mice, Inbred C57BL* ; Neuroinflammatory Diseases* ; Heart Arrest*/complications ; Brain-Gut Axis*/drug effects ; Brain-Gut Axis*/physiology; Animals ; Male ; Mice ; Cell Line ; Inflammation/pathology
    • Abstract:
      Cardiac arrest (CA) is one of the most common illnesses worldwide. Post-CA brain injury (PCABI) is a major cause of death and poor recovery in CA patients and the current CA treatments are not very effective. The microbiome-gut-brain axis has been found to significantly affect brain ischemia injury. Furthermore, in ischemic stroke patients, short-chain fatty acids (SCFA), especially sodium butyrate (SB), have been observed to promote neuroprotective effects by modulating inflammatory response and microglial polarization in the cortex. However, the precise mechanism of SB on CA-induced injury remains elusive. Therefore, this research study established an oxygen-glucose deprivation and reoxygenation (OGD/R) model using BV-2 microglial and HT22 cells to simulate cerebral ischemia/reperfusion injury in vitro and a potassium chloride-induced CA mouse model to mimic CA in vivo. The data revealed that SB markedly improved neurological scores and reduced neuronal death and apoptosis. Moreover, it reduced M1 microglia and neuroinflammation in CA mice. In addition, SB increased intestinal integrity and alleviated systemic inflammation. The 16S rDNA sequencing analysis indicated that SB intervention mitigated CA-induced gut microbiota dysbiosis and SCFA depletion. It was also observed that CA mice's brain and OGD/R-exposed BV2 cells had substantially increased levels of MyD88, phosphorylated NF-κB p65, and TLR4 proteins, which were reduced after SB treatment. In summary, this study revealed that SB can protect against cerebral ischemia-reperfusion injury by controlling microglia polarization and microbiome-gut-brain axis to inhibit brain inflammation via the TLR4/MyD88/NF-κB pathway.
      Competing Interests: Declarations. Ethics approval and consent to participate: All in vivo analyses were authorized by the Laboratory Animal Centre of Wuhan University (No. WDRM 20171204). Consent for publication: All authors approved the final manuscript and the submission to this journal. Competing Interests: The authors declare no competing interests.
      (© 2025. The Author(s).)
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    • Grant Information:
      No. 81772039 National Natural Science Foundation of China; No. 2022020801010474 Knowledge Innovation Program Project of Wuhan Municipal Science and Technology Bureau; CZ2024020001 Project of Healthcare Talent "Chutian Talent Program" in Hubei Province
    • Contributed Indexing:
      Keywords: Cardiac arrest; Gut microbiota; Microglia; Neuroinflammation; Sodium butyrate; TLR4/MyD88/NF-κB pathway
    • Accession Number:
      0 (Myeloid Differentiation Factor 88)
      0 (Toll-Like Receptor 4)
      0 (NF-kappa B)
      107-92-6 (Butyric Acid)
    • Publication Date:
      Date Created: 20250218 Date Completed: 20250218 Latest Revision: 20250220
    • Publication Date:
      20250220
    • Accession Number:
      PMC11834616
    • Accession Number:
      10.1186/s13041-025-01179-w
    • Accession Number:
      39962509