11/19/2022 0 Comments Sonic the hedgehog 1 2013Therefore, understanding of the mechanism by which the integrity of TJs is maintained and the ZO-1, occludin, claudin-5 expression is regulated has potential implication for the treatment of cerebral ischemia.Ī number of cytokines could mediate the change of BBB after cerebral ischemia. Zonula occludens-1 (ZO-1), occludin, claudin-5 proteins are important components of TJs structure and are implicated in the maintenance of integrity of TJs. TJs reduce the permeability of cerebral vessels by restricting the free molecular exchange between blood and brain tissues, and structural damage of TJs could cause the leakage of BBB and brain edema. The principal structures that serve the function of the barrier are the tight junctions (TJs). Stroke leads to the disruption of the blood-brain barrier (BBB), which increases the permeability of the brain microvasculature and eventually results in brain edema. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by grants 81070938 from the Program of National Natural Science Foundation of China, grant 81101905 from the Program of National Natural Science Foundation of China, New Century Excellent Talents in University NCET-10-0406 and the Fundamental Research Funds for the Central Universities, HUST No.2010JC028, HUST No. Received: FebruAccepted: JPublished: July 23, 2013Ĭopyright: © 2013 Xia et al. PLoS ONE 8(7):Įditor: Renping Zhou, Rutgers University, United States of America (2013) Recombinant Human Sonic Hedgehog Protein Regulates the Expression of ZO-1 and Occludin by Activating Angiopoietin-1 in Stroke Damage. This study suggests that, under ischemic insults, Shh triggers Ang-1 production predominantly in astrocytes, and the secreted Ang-1 acts on BMECs, thereby upregulating ZO-1 and occludin to repair the tight junction and ameliorate the brain edema and BBB leakage.Ĭitation: Xia Y-p, He Q-w, Li Y-n, Chen S-c, Huang M, Wang Y, et al. Shh also increased ZO-1, occludin and Ang-1 expression in BMECs, while cyclopamine and Ang-1-neutralizing antibody inhibited the effects of Shh on the ZO-1 and occludin expression, respectively. Results show that the Ang-1 protein level in the culture medium of Shh-treated astrocytes is significantly higher. Primary brain microvessel endothelial cells (BMECs) and astrocytes were pre-treated with Shh, cyclopamine, Ang-1-neutralizing antibody, and subjected to oxygen-glucose deprivation (OGD). Blockage of Shh with cyclopamine abolishes the effects of Shh on brain edema, BBB permeability and ZO-1, occludin, Ang-1 expression. Moreover, Shh increases zonula occludens-1 (ZO-1), occludin and angiopiotetin-1 (Ang-1) expression in the ischemic penumbra. By employing permanent middle cerebral artery occlusion (pMCAO) model, we find that Shh significantly decreases brain edema and preserves BBB permeability. This study examines the regulating effect of Sonic Hedgehog (Shh) on the permeability of the blood-brain barrier (BBB) in cerebral ischemia.
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