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Hippo/YAP signaling pathway mitigates blood-brain barrier disruption after cerebral ischemia/reperfusion injury
- Source :
- Behavioural brain research. 356
- Publication Year :
- 2018
-
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.
- Subjects :
- Male
Ischemia
Brain Edema
Pharmacology
Protein Serine-Threonine Kinases
Blood–brain barrier
Neuroprotection
Article
Dexamethasone
Cerebral edema
Brain Ischemia
Rats, Sprague-Dawley
03 medical and health sciences
Behavioral Neuroscience
0302 clinical medicine
Medicine
Animals
030304 developmental biology
0303 health sciences
Tight junction
business.industry
Brain
Infarction, Middle Cerebral Artery
YAP-Signaling Proteins
medicine.disease
Rats
medicine.anatomical_structure
Neuroprotective Agents
Apoptosis
Blood-Brain Barrier
Reperfusion Injury
Signal transduction
business
Apoptosis Regulatory Proteins
Reperfusion injury
030217 neurology & neurosurgery
Acyltransferases
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 18727549
- Volume :
- 356
- Database :
- OpenAIRE
- Journal :
- Behavioural brain research
- Accession number :
- edsair.doi.dedup.....5b8091b5c69833df28faa9b320dc3f3e