Hippo/YAP signaling pathway mitigates blood-brain barrier disruption after cerebral ischemia/reperfusion injury.

Abstract

Ischemia/reperfusion (I/R) injuries commonly lead to breakdown of the blood-brain barrier (BBB). Restoration of the BBB can relieve neurologic damage caused by I/R injuries. The Hippo/YAP signaling pathway mediates cell proliferation, regulated cell death, and differentiation in various organisms and has been shown to participate in the restoration of the heart after I/R. In this study, we investigated whether the Hippo/YAP pathway plays a role in I/R injury in brain, especially in regard to I/R-induced BBB breakdown. The results of our study indicate that I/R injury led to an overall decrease in activity of the core proteins, YAP and TAZ, over a 24-h period. The most dramatic change was observed 1.5 h after reperfusion. In rats that underwent 1.5 h of reperfusion, intraperitoneal injection of YAP agonist dexamethasone activated YAP and TAZ and led to improved neurologic function, smaller brain infarct sizes, increased levels of tight junction proteins, decreased BBB permeability, decreased cerebral edema, and less apoptosis. Our results suggest that YAP exerts neuroprotective effects on the damaged brain that are likely related to restoration of the BBB.

• Authors: Pian Gong, Zhan Zhang, Changlin Zou, Qi Tian, Xuemei Chen, Michael Hong, Xi Liu, Qianxue Chen, Zhou Xu, Mingchang Li, Jian Wang
• Journal: Behavioural brain research (Behav Brain Res) Vol. 356 Pg. 8-17 (01 01 2019) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 30092249 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Neuroprotective Agents
• Transcription Factors
• YAP-Signaling Proteins
• Yap1 protein, rat
• Dexamethasone
• Acyltransferases
• Tafazzin protein, rat
• Protein Serine-Threonine Kinases

Topics

• Acyltransferases
• Animals
• Apoptosis Regulatory Proteins (metabolism, physiology)
• Blood-Brain Barrier (metabolism)
• Brain (metabolism)
• Brain Edema (physiopathology)
• Brain Ischemia (physiopathology)
• Dexamethasone (pharmacology)
• Infarction, Middle Cerebral Artery (physiopathology)
• Male
• Neuroprotective Agents (pharmacology)
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (physiopathology, prevention & control)
• Signal Transduction (physiology)
• Transcription Factors (metabolism)
• YAP-Signaling Proteins