Hippo/YAP signaling pathway mitigates blood-brain barrier disruption after cerebral ischemia/reperfusion injury
Authors: Xi Liu
Qianxue Chen
Qi Tian
Changlin Zou
Jian Wang
Pian Gong
Xuemei Chen
Mingchang Li
Michael Hong
Zhan Zhang
Zhou Xu
Journal: Behavioural Brain Research (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Blood-brain barrier; Ischemia/reperfusioninjury; Signaling pathway.
Affiliations: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China., Department of Respiratory Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China., Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, Henan, PR China., Department of Anesthesiology and Critical Care Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, PR China. Electronic address: ., Department of Anesthesiology and Critical Care Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 From the group means in Fig 2A and Fig 4A, it can reasonably be expected that the two I R-3h groups were not the same group. However, their  representative images of TTC-stained brain slices in sub-figures C were most probably the same, see detailed side-by-side comparison. Also, the slices in Fig 2C are much more blurred and more loosely arranged. ![file] ![file] , 
 Four blobs on the right of the GAPDH in Fig. 1B and beta-actin in Fig. 5A show unexpectedly similarity. See the side-by-side comparison in high magnification, especially when color map of the images was adjusted to reveal more subtle details. ![file] , 
 Thanks very much for your kindly remind. We are checking our data and we will contact the journal ASAP if necessary. , 
 #2 Thanks very much for your kindly remind. We are checking our data and we will contact the journal ASAP if necessary. ,