Article

Social isolation alters neuroinflammatory response to stroke

Departments of Neuroscience and Psychology and Institute of Behavioral Medicine Research, Ohio State University, 29 Psychology Building, 1835 Neil Avenue, Columbus, OH 43210, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/2009; 106(14):5895-900. DOI: 10.1073/pnas.0810737106
Source: PubMed

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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    • "Mechanistically, rodent models have shown that inflammation acts as a mediator between the amount of social isolation and reduced white matter integrity (Hermes et al., 2006; Karelina et al., 2009). Our results are also qualitatively consistent with this pathway in that reduced social network diversity correlated with reduced white matter integrity and increased systemic inflammation. "
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    • "It should perhaps not be surprising that the absence of these connections threatens the health, life, and genetic legacy of members of many different social species. For instance, social isolation has been shown to decrease the lifespan of the fruit fly, Drosophilia melanogaster (Ruan & Wu, 2008); promote the development of obesity and type 2 diabetes in mice (Nonogaki, Nozue, & Oka, 2007); exacerbate the infarct size and edema and decrease post-stroke survival rate following experimentally induced stroke in mice (Karelina et al., 2010); delay the positive effects of running on adult neurogenesis in rats (Stranahan, Khalil, & Gould, 2006); increase the activation of the sympathetic adrenomedullary response to acute stressors in rats (Dronjak, Gavrilovic, Filipovic, & Radojcic, 2004); decrease the expression of genes regulating glucocorticoid response in the frontal cortex of piglets (Poletto, Steibel, Siegford, & Zanella, 2006); decrease open field activity, increase basal cortisol concentrations, and decrease lymphocyte proliferation to mitogens in pigs (Kanitz, Tuchscherer, Puppe, Tuchschere, & Stabenow, 2004); increase morning rises in cortisol in squirrel monkeys (Lyons, Ha, & Levine, 1995); and elevate 24 hr urinary catecholamines and oxidative stress in the Watanabe heritable hyperlipidemic rabbit (Nation et al., 2008). Humans are born to one of the longest periods of dependency of any species and are dependent on conspecifics across the lifespan to survive and prosper. "
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    • "It should perhaps not be surprising that the absence of these connections threatens the health, life, and genetic legacy of members of many different social species. For instance, social isolation has been shown to decrease the lifespan of the fruit fly, Drosophilia melanogaster (Ruan & Wu, 2008); promote the development of obesity and type 2 diabetes in mice (Nonogaki, Nozue, & Oka, 2007); exacerbate the infarct size and edema and decrease post-stroke survival rate following experimentally induced stroke in mice (Karelina et al., 2010); delay the positive effects of running on adult neurogenesis in rats (Stranahan, Khalil, & Gould, 2006); increase the activation of the sympathetic adrenomedullary response to acute stressors in rats (Dronjak, Gavrilovic, Filipovic, & Radojcic, 2004); decrease the expression of genes regulating glucocorticoid response in the frontal cortex of piglets (Poletto, Steibel, Siegford, & Zanella, 2006); decrease open field activity, increase basal cortisol concentrations, and decrease lymphocyte proliferation to mitogens in pigs (Kanitz, Tuchscherer, Puppe, Tuchschere, & Stabenow, 2004); increase morning rises in cortisol in squirrel monkeys (Lyons, Ha, & Levine, 1995); and elevate 24 hr urinary catecholamines and oxidative stress in the Watanabe heritable hyperlipidemic rabbit (Nation et al., 2008). Humans are born to one of the longest periods of dependency of any species and are dependent on conspecifics across the lifespan to survive and prosper. "
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