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Updated: Mar 20, 2026
Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction
Published on: May 7, 2015
Resveratrol pretreatment modulates SUR1-TRPM4 expression induced by oxygen-glucose deprivation/reoxygenation in brain
Iván Alquisiras Burgos1, Arturo Hernández Cruz2, Penélope Aguilera1
1Laboratorio de Patología Vascular Cerebral, Instituto Nacional de neurología y Neurocirugía Manuel Velasco Suárez, CDMX, México.
Objective:
Cerebral edema is a major contributor to mortality in diverse pathologies; regretfully, no effective therapies can reduce the associated damage. In cerebral ischemia, ionic edema formation is mediated by the sulfonylurea receptor 1 (SUR1)/transient receptor potential melastatin 4 (TRPM4) complex expressed in brain endothelial cells. Given that Resveratrol reduces the damage induced in human brain endothelial cells (HBEC-5i) subjected to oxygen-glucose deprivation (OGD)/reoxiygenation (R) by down-regulating SUR1 expression, we aimed to determine whether Resveratrol modulates SUR1-TRPM4 activity in this model.
Methods:
HBEC-5i cells were exposed to OGD for 2 h followed by 24 h of R. Intracellular Na+ accumulation, measured with the Na-sensitive fluorescence probe coronaNa Green, was used as an indicator of SUR1-TRPM4 activity. Immunofluorescence assays were performed to evaluate SUR1 and TRPM4 expression. Resveratrol (5 μM) was administered during OGD/R. Diazoxide was used to identify responding cells.
Results:
Resveratrol reduced the increase in intracellular Na+ induced by OGD/R and linked to SUR1/TRPM4 activation. While the basal SUR1 and TRPM4 expression levels were low, OGD/R induced their overexpression. Nonetheless, their intracellular distribution indicated incomplete co-localization. A subset of cells showed Na+ elevation after OGD/R, suggesting that although many cells expressed SUR1 and TRPM4, most did not form functional complexes. Diazoxide increased Na+ influx exclusively in 'responding' cells, confirming functional SUR1-TRPM4 activity in this subpopulation.
Conclusion:
SUR1-TRPM4 becomes functionally expressed in a subset of HBEC-5i during OGD/R and pretreatment with Resveratrol attenuated this response. Early modulation of SUR1-TRPM4 by Resveratrol may represent a potential strategy to limit ionic edema.
