Social isolation alters neuroinflammatory response to stroke

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.focal cerebral ischemia ͉ neuroinflammation

Social interaction modulates autonomic, inflammatory, and depressive-like responses to cardiac arrest and cardiopulmonary resuscitation

“…Previous reports have demonstrated the ability of social behavior to modulate immune function (23,30,31) and inflammatory responses to cerebral ischemia (23,24,29). Although the present study did not find significant housing differences in central IL-6, robust differences were detected for the proinflammatory cytokines IL-1β and TNFα.…”

“…Related to, but distinct from, levels of depression, perceived social isolation is a significant predictor of all-cause morbidity and mortality, on par with obesity and smoking (9). Similarly, socially isolated rodents display elevated depressive-like behavior following nerve injury (22), and social isolation exacerbates neuroinflammation and cell death following cerebral ischemia (23,24).…”

Individual housing of female mice: influence on postsurgical behaviour and recovery

“…However, male mice also show a preference for social contact, preferring to sleep in proximity to a familiar male 23 and seem to profit from social housing after challenging events like stroke or nerve injury. 24,25 In conclusion, although behaviours related to subjective wellbeing of mice decreased after surgery and anaesthesia, most behaviours, except burrowing performance, were too variable to reveal significant differences between housing conditions. From the overall results of our study, we cannot claim that postsurgical social housing is truly superior over single housing.…”

When is it socially acceptable to feel sick?

“…A study of female mice bearing ovarian carcinoma suggested that social housing was able to reduce depressive-like symptoms [61], as quantified by a sucrose intake test. In an experimental model of stroke in rats, social housing (males housed with ovariectomized females) reduced ischaemic damage and mortality through a mechanism that appears to be mediated by changes in the inflammatory response [62]. While this study did not focus on behavioural alterations, it illustrates how for certain diseases social housing might be beneficial.…”