Acute hypoxia activates the neuroimmune system, which diabetes exacerbates

Daniel R. Johnson, Jason C. O'Connor, Matthew E. Hartman, Richard I. Tapping, Gregory G. Freund

    Research output: Contribution to journalArticlepeer-review


    Acute hypoxia is experienced in an array of ailments and conditions, including asthma, chronic obstructive pulmonary disease, heart failure, sleep apnea, acute hypotension, and blast lung injury. Classically, infection activates the neuroimmune system, causing loss of interest in the social environment. We report that the non-infectious stimulus acute hypoxia triggers neuroimmune system activation (NSA), causing loss of interest in the social environment, and that recovery from hypoxia-induced NSA is impaired in a mouse model of type 2 diabetes. Importantly, recovery from the behavioral consequences of hypoxia-induced NSA was nearly ablated in MyD88 (myeloid differentiation factor 88) knock-out mice and in mice intracerebroventricularly administered the caspase-1 inhibitor ac-YVAD-CMK (ac-Tyr-Val-Asp-2,6- dimethylbenzoyloxymethylketone). Diabetic mice had prolonged recovery from NSA that could be halved by administration of subcutaneous interleukin-1 (IL-1) receptor antagonist (RA). These results show that acute hypoxia activates the IL-1β arm of the neuroimmune system, which diabetes exacerbates and treatment with IL-1RA ameliorates.

    Original languageEnglish (US)
    Pages (from-to)1161-1166
    Number of pages6
    JournalJournal of Neuroscience
    Issue number5
    StatePublished - Jan 31 2007


    • Caspase-1
    • Hypoxia
    • IL-1 receptor antagonist
    • IL-1β
    • Innate immunity
    • Myeloid differentiation factor 88
    • Neuroimmunity
    • Type 2 diabetes

    ASJC Scopus subject areas

    • General Neuroscience


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