Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
Acta Neuropathol. 2012 Sep;124(3):425-38. doi: 10.1007/s00401-012-0990-8. Epub 2012 May 5.
Social isolation (SI) is increasingly recognized as a risk factor for stroke. Individuals with lack of social support systems have an increased incidence of stroke, poorer recovery, and greater functional decline after injury compared to individuals with social support. Attesting to the importance of social factors in stroke outcome is that these same effects can be reproducibly demonstrated in animals; social interaction improves behavioral deficits and reduces damage after experimental stroke, whereas SI enhances injury. The mechanism by which SI exacerbates injury is unclear. We investigated the role of nuclear factor-kappaB (NF-κB) signaling in male mice that were pair housed (PH) with an ovariectomized female prior to random assignment into continued PH or SI for 7 days prior to middle cerebral artery occlusion. The effects of SI on infarct volume and functional recovery were assessed at 72 h post-stroke. Nuclear NF-κB levels and activity were assessed by Western blot and transcriptional assays. SI significantly exacerbated infarct size in both male and female mice compared to PH mice. SI mice had delayed functional recovery compared to PH mice. An elevation of systemic IL-6 levels, increased nuclear NF-κB transcriptional activity, and enhanced nuclear translocation of NF-κB was seen in SI stroke animals. Interference with NF-κB signaling using either a pharmacological inhibitor or genetically engineered NF-κB p50 knockout mice abolished the detrimental effects of SI on both infarct size and functional recovery. This suggests that NF-κB mediates the detrimental effects of SI.
社交隔离（SI）日益被认为是中风的一个风险因素。与具有社会支持系统的个体相比，缺乏社会支持系统的个体中风发病率更高，康复效果更差，受伤后功能下降幅度更大。证明社会因素在中风结果中的重要性的是，这些相同的影响可以在动物中重复证明；社交互动可改善行为缺陷，并减少实验性中风后的损伤，而 SI 则会加重损伤。SI 加剧损伤的机制尚不清楚。我们研究了核因子-κB（NF-κB）信号在雄性小鼠中的作用，这些雄性小鼠在随机分配到继续 PH 或 SI 之前，与去卵巢的雌性小鼠进行配对饲养（PH），并在进行大脑中动脉闭塞前进行了 7 天的 SI。在中风后 72 小时评估 SI 对梗死体积和功能恢复的影响。通过 Western blot 和转录测定评估核 NF-κB 水平和活性。与 PH 小鼠相比，SI 显著加重了雄性和雌性小鼠的梗死体积。与 PH 小鼠相比，SI 小鼠的功能恢复延迟。在 SI 中风动物中观察到全身 IL-6 水平升高、核 NF-κB 转录活性增加和 NF-κB 核易位增强。使用药理学抑制剂或基因工程 NF-κB p50 敲除小鼠干扰 NF-κB 信号通路，消除了 SI 对梗死体积和功能恢复的不利影响。这表明 NF-κB 介导了 SI 的有害影响。
