Ischemia‐induced endothelial cell swelling and mitochondrial dysfunction are augmented by the pro‐inflammatory chemokine, MCP‐1, but attenuated by dietary polyphenols in vitro

Polyphenols possess anti‐oxidant and anti‐inflammatory properties. Oxidative stress (OS)and inflammation have been implicated in the pathogenesis of brain edema in cerebral ischemia. OS and pro‐inflammatory cytokines damage endothelial cells/neurovascular unit. The resultant breakdown of the blood‐brain barrier contributes to vasogenic edema and may also contribute to endothelial cell swelling, a component of cytotoxic edema. We investigated the protective effects of polyphenols in bEND3 endothelial cultures subjected to 5 hr oxygen‐glucose deprivation (OGD). A polyphenol‐rich extract from green tea (GT), a polyphenol trimer from cinnamon, and resveratrol prevented the OGD‐induced rise in mitochondrial free radicals, cell swelling, and the dissipation of the inner mitochondrial membrane potential. Monocyte chemoattractant protein (MCP‐1), a chemokine, but not TNF‐α or IL‐6, augmented the cell swelling. The effect of MCP‐1 was attenuated by the polyphenols. Cyclosporin A, a blocker of the mitochondrial permeability transition pore, did not attenuate cell swelling but BAPTA‐AM, an intracellular calcium chelator did, indicating a role of [Ca2+] but not the mPT in cell swelling. These results indicate that the polyphenols reduce mitochondrial ROS and subsequent cell swelling in endothelial cells following ischemic injury and thus may reduce brain edema and associated neural damage in ischemia.