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Ischemic Preconditioning Alleviates Cerebral Ischemia–Reperfusion Injury by Interfering With Glycocalyx

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Abstract

Ischemic preconditioning (IPC) could protect the blood–brain barrier (BBB), but the underlying mechanism is not well understood. This preclinical study aimed to investigate whether glycocalyx could be involved in the neuroprotective effect of IPC on cerebral ischemia–reperfusion injury (IRI) and the possible mechanism in rat middle cerebral artery occlusion/reperfusion (MCAO/R) model. Neurological deficit scores, infarct volume, and brain edema were measured to assess the neuroprotection of IPC. Several serum biomarkers related to glycocalyx damage, such as hyaluronic acid (HA), heparan sulfate (HS), and syndecan-1 (SYND1), were evaluated, and their changes were normalized to the ratio of postoperative/preoperative concentration. Western blot and immunofluorescence were used to evaluate the content and cellular location of HA-related metabolic enzymes. This study found that (1) IPC improved brain infarction and edema, neurological impairment, and BBB disruption in IRI rats; (2) IPC significantly up-regulated HA ratio and down-regulated HS ratio, but did not affect SYND1 ratio compared with the IRI group. Moreover, the increased HA ratio was negatively related to brain edema and neurological deficit score. (3) IPC affected HA metabolism by up-regulating hyaluronate synthase-1 and matrix metalloproteinase-2, and down-regulating hyaluronidase-1 in brain tissue. Together, this is the first report that the neuroprotective effect of IPC on IRI may be mediated through interfering with glycocalyx in the MCAO/R model.

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Data Availability

The data underlying this article will be shared upon reasonable request to the corresponding author.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (8207147) and the Science and Technology Project Plan of Liao Ning Province (2019JH2/10300027).

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Authors and Affiliations

  1. Department of Neurology, General Hospital of Northern Theater Command, 83 Wen Hua Road, Shenyang, 110016, China

    Yi-Na Zhang, Qiong Wu, Nan-Nan Zhang & Hui-Sheng Chen

  2. Department of Neurology, General Hospital of Northern Theater Command of China Medical University, Shenyang, 110013, China

    Yi-Na Zhang

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Contributions

H. S. C. designed the experiment and critically edited the manuscript. Y. N. Z., Q. W., and N. N. Z. performed the experiment. Y. N. Z. wrote the draft of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hui-Sheng Chen.

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The study was approved by the Institutional Animal Care and Use Committee of General Hospital of Northern Theater Command (Ethics Number: 2019017).

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Zhang, YN., Wu, Q., Zhang, NN. et al. Ischemic Preconditioning Alleviates Cerebral Ischemia–Reperfusion Injury by Interfering With Glycocalyx. Transl. Stroke Res. 14, 929–940 (2023). https://doi.org/10.1007/s12975-022-01081-w

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