Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in
Zong-Jian Liu1,2,3, Chen Chen2,3, Xiao-Rong Li2,3
1Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
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.
