Specific Role of Tight Junction Proteins Claudin-5, Occludin, and ZO-1 of the Blood–Brain Barrier in a Focal Cerebral Ischemic Insult (original) (raw)

Abstract

Blood–brain barrier (BBB) leakage plays a key role in cerebral ischemia–reperfusion injury. It is quite necessary to further explore the characteristic and mechanism of BBB leakage during stroke. We induced a focal cerebral ischemia model by transient middle cerebral artery occlusion in male rats for defining the time course of BBB permeability within 120 h following reperfusion and evaluate the specific role of tight junction (TJ) associated proteins claudin-5, occludin, and ZO-1 as well as protein kinase C delta (PKCδ) pathway in BBB leakage induced by reperfusion injury. We verified a bimodal increase in the permeability of the BBB following focal ischemia by Evans blue assay. Two peaks of BBB permeability appeared at 3 h and 72 h of reperfusion after 2 h focal ischemia, respectively. The leak at the endothelial cell was represented at the level of transmission electron microscopy. TTC staining results showed increased infarct size with time after cerebral ischemia reperfusion. The mRNA and protein expression levels of these three TJ associated proteins were significantly decreased compared with the sham-operated group within 120 h of reperfusion, corresponding to the time-dependent change of the biphasic pattern in BBB leakage. The redistribution of claudin-5, occludin, and ZO-1 in ischemia brain microvascular endothelial cells was observed at the same time points. In addition, Western blot assay revealed PKCδ level was also significantly increased in a similar biphasic pattern to above results within 120 h after cerebral ischemia–reperfusion. This study demonstrates the timing of TJ associated proteins claudin-5, occludin, and ZO-1 in light of BBB permeability associated with cerebral ischemia reperfusion, and suggests PKCδ pathway may participate in TJ barrier open and BBB leakage during reperfusion injury in a time-dependent manner.

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Acknowledgments

This work is supported by grants from the Natural Science Foundation of China (No. 30670723, 30700249, 30700861, 30800451, 30872656, and 30973079), the special fund for Scientific Research of Doctor-degree Subjects in Colleges and Universities (No. 20092104110015), and Shenyang Science and Technology Plan Projects (No. F10-205-1-22 and F10-205-1-37).

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Authors and Affiliations

1. Department of Neurobiology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China
   Haixia Jiao, Ping Wang & Yixue Xue
2. Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China
   Haixia Jiao, Ping Wang & Yixue Xue
3. Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning Province, 110001, People’s Republic of China
   Zhenhua Wang
4. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, People’s Republic of China
   Yunhui Liu
5. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China
   Yixue Xue

Authors

1. Haixia Jiao
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2. Zhenhua Wang
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3. Yunhui Liu
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4. Ping Wang
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5. Yixue Xue
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Correspondence toYixue Xue.

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Haixia Jiao and Zhenhua Wang contributed equally to this work.

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Jiao, H., Wang, Z., Liu, Y. et al. Specific Role of Tight Junction Proteins Claudin-5, Occludin, and ZO-1 of the Blood–Brain Barrier in a Focal Cerebral Ischemic Insult.J Mol Neurosci 44, 130–139 (2011). https://doi.org/10.1007/s12031-011-9496-4

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• Received: 18 December 2010
• Accepted: 19 January 2011
• Published: 12 February 2011
• Issue Date: June 2011
• DOI: https://doi.org/10.1007/s12031-011-9496-4

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