Changes in cerebral autoregulation and blood biomarkers after remote ischemic preconditioning

Zhen-Ni Guo, Wei-Tong Guo, Jia Liu, Junlei Chang, Hongyin Ma, Peng Zhang, Fu-Liang Zhang, Ke Han, Han-Hwa Hu, Hang Jin, Xin Sun, David Martin Simpson, Yi Yang, Zhen-Ni Guo, Wei-Tong Guo, Jia Liu, Junlei Chang, Hongyin Ma, Peng Zhang, Fu-Liang Zhang, Ke Han, Han-Hwa Hu, Hang Jin, Xin Sun, David Martin Simpson, Yi Yang

Abstract

Objective: To determine the effect of remote ischemic preconditioning (RIPC) on dynamic cerebral autoregulation (dCA) and various blood biomarkers in healthy adults.

Methods: A self-controlled interventional study was conducted. Serial measurements of dCA were performed at 7 time points (7, 9, and 11 am; 2, 5, and 8 pm, and 8 am on the next day) without or with RIPC, carried out at 7:20 to 8 am. Venous blood samples were collected at baseline (7 am) and 1 hour after RIPC, and blood biomarkers, including 5 neuroprotective factors and 25 inflammation-related biomarkers, were measured with a quantitative protein chip.

Results: Fifty participants were enrolled (age 34.54 ± 12.01 years, 22 men). Compared with the results on the day without RIPC, dCA was significantly increased at 6 hours after RIPC, and the increase was sustained for at least 24 hours. After RIPC, 2 neuroprotective factors (glial cell-derived neurotrophic factor and vascular endothelial growth factor-A) and 4 inflammation-related biomarkers (transforming growth factor-β1, leukemia inhibitory factor, matrix metallopeptidase-9, and tissue inhibitor of metalloproteinase-1) were significantly elevated compared with their baseline levels. Conversely, monocyte chemoattractant protein-1 was significantly lower compared with its baseline level.

Conclusions: RIPC induces a sustained increase of dCA from 6 to at least 24 hours after treatment in healthy adults. In addition, several neuroprotective and inflammation-related blood biomarkers were differentially regulated shortly after RIPC. The increased dCA and altered blood biomarkers may collectively contribute to the beneficial effects of RIPC on cerebrovascular function.

Clinicaltrialsgov identifier: NCT02965547.

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Flowcharts and protocols of the…
Figure 1. Flowcharts and protocols of the study
(A) Flowcharts of the study. (B) Study protocols. ABP = arterial blood pressure; DCA = dynamic cerebral autoregulation; HR = heart rate; RIPC = remote ischemic preconditioning.
Figure 2. Autoregulatory parameter and statistical analysis…
Figure 2. Autoregulatory parameter and statistical analysis of dCA, MAP, and HR
(A) Autoregulatory parameter derived from the transfer function analysis. (B) Statistical analysis of dynamic cerebral autoregulation (dCA), mean arterial pressure (MAP), and heart rate (HR) by serial measurements. *p < 0.05 for comparison between the control day and remote ischemic preconditioning (RIPC) day.
Figure 3. Heat map of quantitative protein…
Figure 3. Heat map of quantitative protein chip of 30 biomarkers
Adip = adiponectin; BDNF = brain-derived neurotrophic factor; β-NGF = β-nerve growth factor; CNTF = ciliary neurotrophic factor; CRP = C-reactive protein; EOT = eotaxin; Fas = tumor necrosis factor receptor superfamily member 6; GDNF = glial cell line–derived neurotrophic factor; GM-CSF = granulocyte-macrophage colony-stimulating factor; IFN-γ= interferon-γ; IL = interleukin; LIF = leukemia inhibitory factor; MCP-1 = monocyte chemotactic protein-1; MIP-1β = macrophage inflammatory protein-1β; MMP, matrix metalloproteinase; NX = blood sample number; RIPC = remote ischemic preconditioning; TARC = thymus and activation-regulated chemokine; TGF-β1= transforming growth factor-β1; TIMP-1 = tissue inhibitor of metalloproteinases-1; TNF-α= tumor necrosis factor-α; VEGF-A = vascular endothelial growth factor A.
Figure 4. Statistical distributions of 7 biomarkers…
Figure 4. Statistical distributions of 7 biomarkers with significant differences
(A) Statistical distributions of the neuroprotective factors vascular endothelial growth factor A (VEGF-A) and glial cell line–derived neurotrophic factor (GDNF) at baseline and 1 hour after remote ischemic preconditioning (RIPC) in each group. (B) Statistical distributions of inflammation-related biomarkers transforming growth factor-β1 (TGF-β1), leukemia inhibitory factor (LIF), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and monocyte chemotactic protein-1 (MCP-1) at baseline and 1 hour after RIPC in each group. Whiskers represent highest and lowest values; middle square represents interquartile values; and middle line indicates median. *Adjusted p < 0.05 for comparison with the baseline level.

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