Research Paper Volume 15, Issue 10 pp 4481—4497

Effects of remote ischemic postconditioning on the pro-inflammatory neutrophils of peripheral blood in acute cerebral infarction

Zhen Liang1,2, *, , Lin Qiu1, *, , Xu Wang1, , Liangshu Feng1, , Yulei Hao1, , Feng Yang1, , Di Ma1, , Jiachun Feng1, ,

  • 1 Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China
  • 2 Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China
* Equal contribution

Received: January 31, 2023       Accepted: May 15, 2023       Published: May 30, 2023
How to Cite

Copyright: © 2023 Liang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Neutrophils play crucial roles in the inflammatory response after acute cerebral infarction (ACI). Previous studies revealed neutrophils are non-homogeneous and can be divided into at least two subtypes, pro-inflammatory and anti-inflammatory, correlated with patients’ prognosis.

Objective: We aimed to explore the correlation between disease severity and peripheral blood neutrophils in patients with ACI and determine whether remote ischemic postconditioning (RIPostC) exerts neuroprotective effects by regulating neutrophils.

Methods: Patients (n = 38) with acute anterior circulation cerebral infarction were assigned to conventional treatment (n = 24; included aspirin, statins, neuro nutrition drugs, and circulation improvement drugs) or RIPostC (n = 14; 7-day ischemia adaptation [complete ischemia of both upper extremities for 5 minutes followed by remission for 5 minutes, 5 repeated cycles, twice a day, started from the morning of the second day of admission] based on conventional treatment) groups, based on their preference. General clinical data and peripheral blood samples were taken three times, in the morning before and 3 and 7 days after treatment. Fifteen adults with non-acute cerebral infarction matched for sex, age, and risk factors were recruited as controls; peripheral blood samples were only collected on the recruitment day. We used flow cytometry to detect the percentage of neutrophils and Real-Time PCR to detect the gene expression of interleukin (IL)-1β in the peripheral blood samples.

Results: The percentage of neutrophils, pro-inflammatory neutrophils (IL-1β high expression in flow cytometry), and IL-1β mRNA expression increased after ACI (P = 0.01, P = 0.001, P < 0.001). The National Institutes of Health Stroke Scale (NIHSS) score of patients with ACI within one day of onset was positively correlated with the percentage of pro-inflammatory neutrophils (R = 0.618, P = 0.043). Pro-inflammatory neutrophils in the RIPostC group decreased compared with those in the conventional treatment group, with the most significant difference observed on Day 7 (P = 0.01). However, the percentage of neutrophils was not statistically different. IL-1β mRNA expression decreased, with the most significant difference on Day 3 (P = 0.004). The NIHSS and Modified Rankin Scale scores for RIPostC decreased more significantly than for conventional treatment (P = 0.002, P = 0.019).

Conclusion: More severe cerebral infarction was associated with a higher percentage of pro-inflammatory neutrophils. The neuroprotective effect of RIPostC may partly be exerted through gene regulation to reduce pro-inflammatory neutrophils.


ALT: Alanine aminotransferase; APTT: Activated partial thromboplastin time; AST: Aspartate amino transferase; BBB: Blood–brain barrier; FIB: Fibrinogen; Glu: Glucose; HbAlc: Glycosylated Hemoglobin; HCY: Homocysteine; HPA: Hypothalamus-Pituitary-Adrenal gland; hs-CRP: high-sensitivity C-reactive protein; IL: Interleukin; INR: International Normalized Ratio; I/R: Ischemic/Reperfusion; LDL-C: Low density lipoprotein cholesterol; MCAO: Middle cerebral artery occlusion; MMP-9: Matrix metalloproteinases 9; mRS: Modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; PT: Prothrombin time; RIPostC: Remote ischemic postconditioning; ROS: Reactive oxygen species; RT-PCR: Real-Time Polymerase Chain Reaction; TC: Total cholesterol; TG: Triglyceride; VitB12: Vitamins B12.