title: Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our results reveal dramatic immune changes during RIPC-afforded neuroprotection against cerebral ischemia.
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.|China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Zong-Jian
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Li
authors.affiliation: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ran
authors.affiliation: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Geng
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Hui-Shan
authors.initials: HS
authors.lastname: Du
authors.affiliation: Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA, USA.
authors.forename: Rehana K
authors.initials: RK
authors.lastname: Leak
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.|China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Beijing, China.
authors.forename: Xun-Ming
authors.initials: XM
authors.lastname: Ji
authors.affiliation: China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Hu
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery; D015850:Interleukin-6 / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009000:Monocytes / Q000502:physiology; D015213:Neuroimmunomodulation / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Cerebral ischemia; Cytokine; Immune cells; Limb remote ischemic preconditioning