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NF-κB contributes to the detrimental effects of social isolation after experimental stroke

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Abstract

Social isolation (SI) is increasingly recognized as a risk factor for stroke. Individuals with lack of social support systems have an increased incidence of stroke, poorer recovery, and greater functional decline after injury compared to individuals with social support. Attesting to the importance of social factors in stroke outcome is that these same effects can be reproducibly demonstrated in animals; social interaction improves behavioral deficits and reduces damage after experimental stroke, whereas SI enhances injury. The mechanism by which SI exacerbates injury is unclear. We investigated the role of nuclear factor-kappaB (NF-κB) signaling in male mice that were pair housed (PH) with an ovariectomized female prior to random assignment into continued PH or SI for 7 days prior to middle cerebral artery occlusion. The effects of SI on infarct volume and functional recovery were assessed at 72 h post-stroke. Nuclear NF-κB levels and activity were assessed by Western blot and transcriptional assays. SI significantly exacerbated infarct size in both male and female mice compared to PH mice. SI mice had delayed functional recovery compared to PH mice. An elevation of systemic IL-6 levels, increased nuclear NF-κB transcriptional activity, and enhanced nuclear translocation of NF-κB was seen in SI stroke animals. Interference with NF-κB signaling using either a pharmacological inhibitor or genetically engineered NF-κB p50 knockout mice abolished the detrimental effects of SI on both infarct size and functional recovery. This suggests that NF-κB mediates the detrimental effects of SI.

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Acknowledgments

This work was supported by National Institutes of Health grants R01 NSO77769 and NS055215 (to L.D.M.) and American Heart Association grant 11POST7430045 to V.R.V, 09SDG2261435 to J.L.

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Authors and Affiliations

  1. Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Venugopal Reddy Venna, Gillian Weston, Sharon E. Benashski, Sami Tarabishy, Fudong Liu, Jun Li & Louise D. McCullough

  2. Department of Neurology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030, USA

    Louise D. McCullough

  3. Department of Psychiatry, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030, USA

    Lisa H. Conti

  4. The Stroke Center at Hartford Hospital, 85 Jefferson Street, Hartford, CT, 06102, USA

    Louise D. McCullough

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  1. Venugopal Reddy Venna
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Correspondence to Louise D. McCullough.

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Venna, V.R., Weston, G., Benashski, S.E. et al. NF-κB contributes to the detrimental effects of social isolation after experimental stroke. Acta Neuropathol 124, 425–438 (2012). https://doi.org/10.1007/s00401-012-0990-8

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