Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses
CNS neuroscience & therapeutics
Cerebral ischemia, Cytokine, Immune cells, Limb remote ischemic preconditioning
AIMS: Remote ischemic preconditioning (RIPC) of a limb is a clinically feasible strategy to protect against ischemia-reperfusion injury after stroke. However, the mechanism underlying RIPC remains elusive. METHODS: We generated a rat model of noninvasive RIPC by four repeated cycles of brief blood flow constriction (5 min) in the hindlimbs using a tourniquet. Blood was collected 1 h after preconditioning and 3 days after brain reperfusion. The impact of RIPC on immune cell and cytokine profiles prior to and after transient middle cerebral artery occlusion (MCAO) was assessed. RESULTS: Remote ischemic preconditioning protects against focal ischemia and preserves neurological functions 3 days after stroke. Flow cytometry analysis demonstrated that RIPC ameliorates the post-MCAO reduction of CD3(+)CD8(+) T cells and abolishes the reduction of CD3(+)/CD161a(+) NKT cells in the blood. In addition, RIPC robustly elevates the percentage of B cells in peripheral blood, thereby reversing the reduction in the B-cell population after stroke. RIPC also markedly elevates the percentage of CD43(+)/CD172a(+) noninflammatory resident monocytes, without any impact on the percentage of CD43(-)/CD172a(+) inflammatory monocytes. Finally, RIPC induces IL-6 expression and enhances the elevation of TNF-α after stroke. CONCLUSION: Our results reveal dramatic immune changes during RIPC-afforded neuroprotection against cerebral ischemia.
Liu, Z., Chen, C., Li, X., Ran, Y., Xu, T., Zhang, Y., Geng, X., Zhang, Y., Du, H., Leak, R. K., Ji, X., & Hu, X. (2016). Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses. CNS neuroscience & therapeutics, 22 (1), 43-52. https://doi.org/10.1111/cns.12448