Protective Effects of Antioxidant Polyphenols Against Hyperglycemia‐Mediated Alterations in Cerebral Endothelial Cells and a Mouse Stroke Model

SCOPE: Hyperglycemia alters cerebral endothelial cell and blood-brain barrier functions, aggravating cerebrovascular complications such as stroke during diabetes. Redox and inflammatory changes play a causal role. This study evaluated polyphenol protective effects on cerebral endothelial cells and in a mouse stroke model during hyperglycemia. METHODS AND RESULTS: Murine bEnd.3 cerebral endothelial cells and a mouse stroke model were exposed to a characterized polyphenol-rich extract of Antirhea borbonica or its predominant constituent caffeic acid, during high glucose condition used to mimic hyperglycemia. Polyphenol effects on redox, inflammatory and vasoactive markers as well as on infarct volume and hemorrhagic transformation were determined. In vitro, polyphenols improved ROS levels, Cu/ZnSOD activity and both Nox4 and Nrf2 gene expression deregulated by high glucose. Polyphenols reduced Nrf2 nuclear translocation, and counteracted NFĸB pathway activation, IL-6 secretion and the altered production of vasoactive markers mediated by high glucose. In vivo, polyphenols reduced cerebral infarct volume and hemorrhagic transformation aggravated by hyperglycemia. Polyphenols attenuated redox changes, increased VE-Cadherin production and decreased neuro-inflammation in infarcted hemisphere. CONCLUSION: Polyphenols protected against hyperglycemia-mediated alterations in cerebral endothelial cells and a mouse stroke model. It will be relevant to assess polyphenol-based strategies to improve cerebrovascular damage and stroke recovery during diabetes. This article is protected by copyright. All rights reserved.