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Combined Ischemic Preconditioning and Resveratrol Improved Bloodbrain Barrier Breakdown via Hippo/YAP/TAZ Signaling Pathway

[ Vol. 18 , Issue. 9 ]

Author(s):

Ganji Hong, Ying Yan, Yali Zhong, Jianer Chen, Fei Tong* and Qilin Ma*   Pages 713 - 722 ( 10 )

Abstract:


Background: Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out.

Objective: The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats.

Methods: Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues.

Results: Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action.

Conclusion: combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway.

Keywords:

Ischemic Preconditioning (IPC), Resveratrol (RES), Hippo/YAP/TAZ, Brain Ischemia/Reperfusion Injury (BI/RI), Blood-Brain Barrier (BBB), Water Content (BWC).

Affiliation:

Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, Department of Rehabilitation Medicine, Zhejiang Chinese Medical University, The Third Clinical Medicine, Hangzhou, Zhejiang, College of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, Department of Rehabilitation Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, School of Pharmaceutical Science, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, 510515, Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen



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