Open AccessRemote Ischemic Preconditioning‐Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses
Author(s) -
Liu ZongJian,
Chen Chen,
Li XiaoRong,
Ran YuanYuan,
Xu Tao,
Zhang Ying,
Geng XiaoKun,
Zhang Yu,
Du HuiShan,
Leak Rehana K.,
Ji XunMing,
Hu XiaoMing
Publication year - 2016
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12448
Subject(s) - medicine , ischemic preconditioning , neuroprotection , ischemia , stroke (engine) , immune system , anesthesia , pharmacology , immunology , mechanical engineering , engineering
Summary 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 CD 3 + CD 8 + T cells and abolishes the reduction of CD 3 + / CD 161a + 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 CD 43 + / CD 172a + noninflammatory resident monocytes, without any impact on the percentage of CD 43 − / CD 172a + 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.