Gamma-glutamylcysteine ethyl ester protects cerebral endothelial cells during injury and decreases blood-brain-barrier permeability after experimental brain trauma

摘要

Oxidative stress is a pathway of injury that is common to almost all neurological conditions. Hence, methods to scavenge radicals have been extensively tested for neuroprotection. However, saving neurons alone may not be sufficient in treating CNS disease. Here, we tested the cytoprotective actions of the glutathione precursor GCEE in brain endothelium. First, oxidative stress was induced in a human brain microvascular endothelial cell line by exposure to H2O2. Addition of GCEE significantly reduced formation of reactive oxygen species, restored glutathione levels which were reduced in the presence of H2O2, and decreased cell death during H2O2-mediated injury. Next, we asked whether GCEE can also protect brain endothelial cells against oxygen-glucose deprivation (OGD). As expected, OGD disrupted mitochondrial membrane potentials. GCEE was able to ameliorate these mitochondrial effects. Concomitantly, GCEE significantly decreased endothelial cell death after OGD. Lastly, our in-vivo experiments using a mouse model of brain trauma show that post-trauma (10 min after CCI) administration of GCEE by intraperitoneal injection results in a decrease in acute blood-brain barrier permeability. These data suggest that the beneficial effects of GCEE on brain endothelial cells and microvessels may contribute to its potential efficacy as a neuroprotective agent in traumatic brain injury.