BACKGROUND:Stroke, traumatic brain injury, or other forms of central nervous system (CNS) injury initiate a local inflammatory response. Compensatory anti-inflammatory pathways are activated to limit secondary damage due to inflammation. The associated release of immunosuppressing neuromodulators can result in system-wide immune dysregulation (CNS injury-induced immune-depression syndrome –CIDS). OBJECTIVE:To establish an experimental stroke model where CIDS can be studied by intravital microscopy (IVM). METHODS:We used the photothrombotic stroke (PTS) model in C57BL/6 mice and studied its effects on peripheral immunity following challenge with lipopolysaccharide (LPS). Leukocyte activation, as well as capillary perfusion of the microcirculation, were assessed using intestinal intravital microscopy (IVM). RESULTS:PTS caused a significant reduction in the number of adhering leukocytes in submucosal venules of the terminal ileum of mice challenged with LPS compared to LPS-challenged animals without stroke. Leukocyte rolling was also impacted by PTS in the submucosal venules. Following stroke, we also observed decreased mucosal functional capillary density (FCD). CONCLUSIONS:Our results suggest that PTS with subsequent LPS challenge poses as a viable model to further study CIDS using intravital microscopy of the intestinal microcirculation.

中文翻译：

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肠道活体显微镜在 CNS 损伤诱导的免疫抑制综合征 (CIDS) 研究中的应用

背景：中风、外伤性脑损伤或其他形式的中枢神经系统 (CNS) 损伤会引发局部炎症反应。补偿性抗炎通路被激活以限制炎症引起的继发性损伤。免疫抑制性神经调节剂的相关释放可导致全系统免疫失调（中枢神经系统损伤诱导的免疫抑制综合征 – CIDS）。目的：建立可通过活体显微镜（IVM）研究CIDS的实验性脑卒中模型。方法：我们在 C57BL/6 小鼠中使用光血栓形成中风 (PTS) 模型并研究其对脂多糖 (LPS) 攻击后外周免疫的影响。使用肠道活体显微镜 (IVM) 评估白细胞活化以及微循环的毛细血管灌注。结果：与没有中风的 LPS 攻击的动物相比，PTS 导致用 LPS 攻击的小鼠回肠末端黏膜下微静脉中粘附的白细胞数量显着减少。白细胞滚动也受到粘膜下静脉中 PTS 的影响。中风后，我们还观察到黏膜功能性毛细血管密度 (FCD) 降低。结论：我们的结果表明，PTS 与随后的 LPS 挑战是一个可行的模型，可以使用肠道微循环的活体显微镜进一步研究 CIDS。