Objective:

The objective of this study is to characterize the effects of edaravone on human brain microvascular endothelial cells in the context of TBI induced oxidative stress and BBB disruption.  

Background:

Traumatic brain injury (TBI) is a leading cause of morbidity worldwide and a major risk factor for neurological disease. TBI triggers overproduction of reactive oxygen species (ROS) including hydrogen peroxide (H202), leading to mitochondrial damage in microvascular endothelial cells, the innermost monolayer of the blood-brain barrier (BBB), resulting in barrier disruption and increased risk for cerebral edema and intracranial hypertension. Edaravone is an FDA-approved free radical scavenger approved for delaying motor neuron degeneration in ALS and has been shown to protect the BBB in diabetic stroke models. The role of edaravone as a BBB protectant in the context of TBI is not yet known.  

Design/Methods:

Human brain microvascular endothelial cells (HBMECs) were seeded in transwell inserts, simulating a BBB monolayer. Cells were exposed to increasing concentrations of edaravone and challenged with H202, a known ROS generated in TBI. Microvascular permeability was measured using FITC-Dextran fluorescent tracer (10 kDa). Cell viability was measured using Calcein AM and ROS formation was measured using ROS detection assay.

Results:

Results indicate that H202 challenged cells resulted in hyperpermeability across the microvascular monolayer. When cells were pretreated with edaravone at 1, 5, and 10 μM for 24 hours, microvascular permeability was restored. Edaravone treatment reduced H202 induced ROS formation and, on its own, did not significantly affect cell viability. However, edaravone did restore viability in challenged cells.

Conclusions: