As well as in brain microvessels of diabetic rats, and a disturbed architectural organization of zonula occludens-1 protein. Similar to other cellular systems, methylglyoxal-treatment promoted carbonyl and oxidative stress in brain endothelial cells. Methylglyoxal induced mitochondrial apoptotic signaling: decreased mitochondrial membrane potential, activated caspases and perturbed the cellular glutathione redox status. These findings indicate that methylglyoxal-induced carbonyl and oxidative stress may play an important role in neurovascular pathology, and brain endothelium can be an early and significant target site of methylglyoxal. The prevention of methylglyoxal-induced injury is in the focus of current research. Aminoguanidine was the first drug extensively studied, and attenuated the development of a range of diabetic vascular complications both in vitro and in vivo. However, due to toxic side effects at high doses, it failed in clinical trials. This compound is considered as a prototype for antiglycation agents and used as a reference molecule in experiments. Recently, a new promising agent, edaravone is investigated for its beneficial effects on brain endothelial cells. Edaravone is a neuroprotective free radical scavenger. It is the active substance of a Japanese medicine, which helps neurological recovery following acute brain and subsequent cerebral infarct. To further reveal the mechanism of protection, brain microvessels and the blood-brain barrier were investigated as potential pharmaceutical targets of edaravone in ABT-199 animal models of stroke. The effect of edaravone alone has been described on barrier function: it promoted tight junction formation via activation of sphingosin-1-phospate signaling pathway and down-regulation of interleukin-1b induced monocyte chemoattractant protein-1 secretion in human microvascular endothelial cells. In a recent study, methylglyoxal-induced decrease in cell viability and methylglyoxal enhanced cell injury by oxygenglucose deprivation were alleviated by pretreatment with edaravone in brain endothelial cells. However, it remained unanswered whether edaravone can also protect against methylglyoxal-induced barrier dysfunction of brain endothelial monolayers. The tight intercellular barrier maintaining low permeability is the fundamental characteristic of brain endothelial cells. Therefore, this study aimed to clarify the effect of edaravone against methylglyoxal-induced barrier and morphological damage. In the experiments the widely used human hCMEC/D3 brain endothelial cell line, and new investigation methods, such as impedance monitoring in multiwell plates and holographic phase contrast imaging were used in addition to viability assays, permeability tests and immunohistochemistry for junctional proteins. Higher incidence of stroke, dementia and Alzheimer’s disease is observed in diabetes mellitus.