Social isolation alters neuroinflammatory response to stroke
Edited by William T. Greenough, University of Illinois, Urbana, IL, and approved February 24, 2009
Abstract
Social isolation has dramatic long-term physiological and psychological consequences; however, the mechanisms by which social isolation influences disease outcome are largely unknown. The purpose of the present study was to investigate the effects of social isolation on neuronal damage, neuroinflammation, and functional outcome after focal cerebral ischemia. Male mice were socially isolated (housed individually) or pair housed with an ovariectomized female before induction of stroke, via transient intraluminal middle cerebral artery occlusion (MCAO), or SHAM surgery. In these experiments, peri-ischemic social isolation decreases poststroke survival rate and exacerbates infarct size and edema development. The social influence on ischemic damage is accompanied by an altered neuroinflammatory response; specifically, central interleukin-6 (IL-6) signaling is down-regulated, whereas peripheral IL-6 is up-regulated, in isolated relative to socially housed mice. In addition, intracerebroventricular injection of an IL-6 neutralizing antibody (10 ng) eliminates social housing differences in measures of ischemic outcome. Taken together, these data suggest that central IL-6 is an important mediator of social influences on stroke outcome.
Acknowledgments.
We thank Zachary Weil and James Walton for technical support and assistance with data analysis and Zachary Weil for critiquing the manuscript. This work was supported by grants from the American Heart Association (Established Investigator Award to A.C.D. and predoctoral fellowship to K.K.), National Institute of Neurological Disorders and Stroke Behavioral Core Grant P30 NS045758 (to A.C.D.), National Institute of Neurological Disorders and Stroke Grant RO1NS40267–05 (to A.C.D.), and National Heart, Lung, and Blood Institute Grant RO1HL080249–01 (to A.C.D.).
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© 2009.
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Received: October 24, 2008
Published online: April 7, 2009
Published in issue: April 7, 2009
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Acknowledgments
We thank Zachary Weil and James Walton for technical support and assistance with data analysis and Zachary Weil for critiquing the manuscript. This work was supported by grants from the American Heart Association (Established Investigator Award to A.C.D. and predoctoral fellowship to K.K.), National Institute of Neurological Disorders and Stroke Behavioral Core Grant P30 NS045758 (to A.C.D.), National Institute of Neurological Disorders and Stroke Grant RO1NS40267–05 (to A.C.D.), and National Heart, Lung, and Blood Institute Grant RO1HL080249–01 (to A.C.D.).
Notes
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0810737106/DCSupplemental.
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The authors declare no conflict of interest.
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Social isolation alters neuroinflammatory response to stroke, Proc. Natl. Acad. Sci. U.S.A.
106 (14) 5895-5900,
https://doi.org/10.1073/pnas.0810737106
(2009).
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