Social interaction modulates the neuroinflammatory response to global cerebral ischemia in male mice

• Published in: Brain research Vol. 1673; pp. 86 - 94
• Main Authors: Gaudier-Diaz, Monica M., Zhang, Ning, Haines, Adam H., Surbhi, Zhou, Min, DeVries, A. Courtney
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2017
• Subjects: Animals; Brain Ischemia - immunology; Brain Ischemia - pathology; Brain Ischemia - psychology; Disease Models, Animal; Gene Expression; Global cerebral ischemia; Glucose - deficiency; Hippocampus - immunology; Hippocampus - pathology; Housing, Animal; Inflammation - metabolism; Inflammation - pathology; Inflammation - psychology; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Male; Mice, Inbred C57BL; Microglia - immunology; Microglia - pathology; Myosin Heavy Chains - metabolism; Neuroinflammation; NF-kappa B p50 Subunit - metabolism; Prefrontal Cortex - immunology; Prefrontal Cortex - pathology; RNA, Messenger - metabolism; Social Behavior; Social isolation; Tumor Necrosis Factor-alpha - metabolism; rtPCR; MHC II; Nfκb; Neuroinflammation; CA/CPR; IL-1β; OGD; IL-6; TNF-α; Social isolation; aCSF; Global cerebral ischemia; Iba-1
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2017.08.008

•Isolation-induced increase of MHC II expression is suggestive of microglial priming.•Social isolation exacerbates the neuroinflammatory response to CA/CPR.•Housing condition prior to an ischemic event is sufficient to modulate inflammation. Social isolation is a risk factor for cardiovascular and cerebrovascular diseases, although the underlying mechanisms remain underspecified. Considering the potential of microglia to become sensitized by stressors and their role in neuroinflammation, we hypothesized that social isolation primes microglia, resulting in an exaggerated neuroimmune response to experimental cerebral ischemia. First, major histocompatibility complex II (MHC II) gene expression, an indicator of microglial priming, was compared between mice that were socially isolated or pair-housed. MHC II increased in the hippocampus and cortex of socially isolated mice, which is suggestive of isolation-induced microglial priming. In experiment 2, isolated and pair-housed mice underwent ∼8min of global cerebral ischemia. Hippocampal mRNA expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was significantly increased among both isolated and pair-housed ischemia groups relative to sham controls. Hippocampal expression of interleukin 1 beta (IL-1β) and cortical TNF-α, IL-1β and IL-6, were significantly increased 24-h post ischemia in isolated mice, but not pair-housed mice, relative to controls. Ischemia-induced increases in microglial cell body area and percent area fraction of ionized calcium binding adaptor molecule 1 (Iba-1) positive staining were also observed in isolated, but not pair-housed mice, relative to controls. For experiment 3, brain sections from socially isolated and pair-housed mice underwent 15min of oxygen glucose deprivation (OGD), an ex vivo model of cerebral ischemia. IL-6 gene expression was significantly elevated following OGD only in hippocampi from mice that had been socially isolated, indicating that isolation prior to ischemia is sufficient to modulate the neuroinflammatory response. Together, these data suggest microglial priming as a possible mechanism underlying the detrimental effects of social isolation on cerebral ischemia outcome.