Social isolation alters neuroinflammatory response to stroke

Edited by William T. Greenough, University of Illinois, Urbana, IL, and approved February 24, 2009
April 7, 2009
106 (14) 5895-5900

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.

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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.).

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 106 | No. 14
April 7, 2009
PubMed: 19307557

Classifications

Submission history

Received: October 24, 2008
Published online: April 7, 2009
Published in issue: April 7, 2009

Keywords

  1. focal cerebral ischemia
  2. neuroinflammation

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.

Authors

Affiliations

Kate Karelina
Departments of aNeuroscience and
Greg J. Norman
Ning Zhang
John S. Morris
Haiyan Peng
Departments of aNeuroscience and
A. Courtney DeVries1 [email protected]
Departments of aNeuroscience and
Psychology and
Institute of Behavioral Medicine Research, Ohio State University, 29 Psychology Building, 1835 Neil Avenue, Columbus, OH 43210

Notes

1
To whom correspondence should be addressed at: Departments of Psychology and Neuroscience and Institute of Behavioral Medicine Research, Ohio State University, 51 Psychology Building, 1835 Neil Avenue, Columbus, OH 43210. Email: [email protected]
Author contributions: K.K. and A.C.D. designed research; K.K., G.J.N., N.Z., J.S.M., and H.P. performed research; K.K. and A.C.D. analyzed data; and K.K. and A.C.D. wrote the paper.

Competing Interests

The authors declare no conflict of interest.

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    Social isolation alters neuroinflammatory response to stroke
    Proceedings of the National Academy of Sciences
    • Vol. 106
    • No. 14
    • pp. 5451-6023

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