Increased Susceptibility of Blood-Brain Barrier to Ischemic Damage by a Diabetic Metabolite Methylglyoxal

Abstract

Ischemic stroke is the major cause of death or disability in diabetic patients. Diabetic patients have higher incidence of stroke, however the underlying molecular mechanisms are not clear. The blood level of methylglyoxal (MG), a byproduct of glycolysis, is significantly increased in patients with diabetes. Several studies have reported that MG might play a key role in vascular dysfunction under diabetic condition. In this study, we investigated if MG disrupts blood-brain barrier (BBB) function and increases the susceptibility of BBB to ischemic damage. Treatment of MG significantly decreased cell viability of bEND.3 cells, an in vitro BBB model. MG increased the permeability in bEND.3 in a dose-dependent manner. In addition, the level of occludin, a tight junction protein, was decreased after exposure to MG. To investigate the change in susceptibility to ischemic damage under high concentration of MG, we exposed bEnd.3 cells to MG for 12 hours prior to oxygen-glucose deprivation (OGD). Cell viability assay revealed an increased ischemic cell death under high level of MG, indicating that MG increased susceptibility to ischemic damage of BBB. Taken together, we demonstrated ischemic disruption of BBB can be enhanced by exposure to MG, suggesting that MG-induced BBB disruption might be a key factor in the susceptible ischemic damage under diabetic condition.