Title:Combined Ischemic Preconditioning and Resveratrol Improved Bloodbrain Barrier Breakdown via Hippo/YAP/TAZ Signaling Pathway
Volume: 18
Issue: 9
Author(s): Ganji Hong, Ying Yan, Yali Zhong, Jianer Chen, Fei Tong*Qilin Ma*
Affiliation:
- School of Pharmaceutical Science, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, 510515,China
- Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen,China
Keywords:
Ischemic Preconditioning (IPC), Resveratrol (RES), Hippo/YAP/TAZ, Brain Ischemia/Reperfusion Injury (BI/RI),
Blood-Brain Barrier (BBB), Brain Water Content (BWC).
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.