Utility of intestinal intravital microscopy for the study of CNS injury-induced immunodepression syndrome (CIDS)

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 rollingwas 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.