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Ischemic Postconditioning Protects the Neurovascular Unit after Focal Cerebral Ischemia/Reperfusion Injury

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Abstract

Recently, cerebral ischemic postconditioning (Postcond) has been shown to reduce infarction volume in cerebral ischemia/reperfusion (I/R) injury. However, it is unclear if ischemic Postcond offers more extensive neuroprotection than current therapies. The aim of this study was to investigate the neuroprotective effects of ischemic Postcond on the neurovascular unit (NVU). A middle cerebral artery occlusion rat model was used; cerebral infarct volumes, neurologic scores, and transmission electron microscopy were evaluated 24 h after reperfusion. We used Evans blue extravasation, immunohistochemistry, and Western blot analyses to evaluate the integrity of the blood brain barrier (BBB) and the distribution and expression of the tight junction (TJ)-associated proteins of claudin-5 and occludin in brain microvessel endothelium. The Postcond group showed significantly reduced infarct volumes and decreased neurologic impairment scores compared to the I/R group. Also, injuries to the cerebral microvascular endothelial cells, astrocytes, and neurons were minimized in the Postcond group. The permeability of the BBB increased in both the I/R and Postcond groups, but the Postcond group showed a significant decrease in permeability than the I/R group. Expression of both claudin-5 and occludin were higher in the Postcond groups compared to the I/R group, but expression of both proteins decreased in the I/R and Postcond groups compared to the sham group. The results of our study suggest that ischemic Postcond is an effective way to reduce injury to neurons, astrocytes, and endothelial cells, to increase protein expressions of TJ-associated proteins, and to improve BBB intergrity affected by focal I/R. Ischemic Postcond could protect the NVU from I/R injury.

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Acknowledgments

This work was supported by the Doctor Start-up Fund of Liaoning Province (20121131) and Fundamental Research Funds of Shengjing Hospital (M995).

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Authors and Affiliations

  1. Department of Neurology, The Affiliated Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, China

    Dong Han, Shuo Zhang, Bin Fan, Lu-lu Wen, Miao Sun, Hong Zhang & Juan Feng

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  1. Dong Han
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  2. Shuo Zhang
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  3. Bin Fan
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  4. Lu-lu Wen
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  5. Miao Sun
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  6. Hong Zhang
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  7. Juan Feng
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Correspondence to Juan Feng.

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Han, D., Zhang, S., Fan, B. et al. Ischemic Postconditioning Protects the Neurovascular Unit after Focal Cerebral Ischemia/Reperfusion Injury. J Mol Neurosci 53, 50–58 (2014). https://doi.org/10.1007/s12031-013-0196-0

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  • DOI: https://doi.org/10.1007/s12031-013-0196-0

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