Annexin A1 Mitigates Blood-Brain Barrier Disruption in a Sepsis-Associated Encephalopathy Model by Enhancing the Expression of Occludin and Zonula Occludens-1 (ZO-1).

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford, UK : Wiley-Blackwell, c2008-
    • Subject Terms:
    • Abstract:
      Aims: This study investigated the protective role of Annexin A1 (ANXA1) in sepsis-associated encephalopathy (SAE) by examining its effects on brain vascular endothelium and blood-brain barrier (BBB) integrity.
      Methods: Mice were divided into four groups: wild type (WT), cecal ligation and puncture (CLP), ANXA1 knockout (ANXA1[-/-]), and ANXA1(-/-) with CLP. Neurobehavioral changes were assessed using the Y-maze test, while BBB integrity was evaluated through Evans blue dye (EBD) staining and permeability tests with fluorescein isothiocyanate (FITC)-dextran.
      Results: Results showed that ANXA1 levels were reduced in septic mice, and its deficiency exacerbated cognitive impairment and survival rate reduction. ANXA1 deficiency also upregulated proinflammatory cytokines and adhesion molecules, worsened BBB impairment, and altered expression of tight junction proteins and VEGF-A/VEGF-R2. In vitro, ANXA1 Ac2-26 prevented LPS-induced increased permeability in bEnd.3 cells by restoring tight junction proteins and reducing VEGF-A/VEGF-R2 expression. Notably, VEGF-A negated the protective effects of ANXA1 Ac2-26.
      Conclusion: The study concludes that ANXA1 reduces BBB permeability to protect against sepsis-induced brain dysfunction via VEGF-A/VEGF-R2 regulation of tight junction proteins, suggesting ANXA1 as a potential therapeutic for SAE.
      (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
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    • Grant Information:
      Sichuan Provincial People's Hospital
    • Contributed Indexing:
      Keywords: VEGF; annexin A1; blood brain barrier; occludin; sepsis‐associated encephalopathy
    • Accession Number:
      0 (Annexin A1)
      0 (Zonula Occludens-1 Protein)
      0 (Occludin)
      0 (Tjp1 protein, mouse)
      0 (annexin A1, mouse)
      0 (Ocln protein, mouse)
    • Publication Date:
      Date Created: 20241227 Date Completed: 20241227 Latest Revision: 20250104
    • Publication Date:
      20250104
    • Accession Number:
      PMC11672249
    • Accession Number:
      10.1111/cns.70173
    • Accession Number:
      39727329