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


Lok J., Leung W., Zhao S., Pallast S., van Leyen K., Guo S., ...More

JOURNAL OF NEUROCHEMISTRY, vol.118, no.2, pp.248-255, 2011 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 118 Issue: 2
  • Publication Date: 2011
  • Doi Number: 10.1111/j.1471-4159.2011.07294.x
  • Title of Journal : JOURNAL OF NEUROCHEMISTRY
  • Page Numbers: pp.248-255

Abstract

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. In this study, we tested the cytoprotective actions of the glutathione precursor gamma-glutamylcysteine ethyl ester (GCEE) in brain endothelium. First, oxidative stress was induced in a human brain microvascular endothelial cell line by exposure to H(2)O(2). Addition of GCEE significantly reduced formation of reactive oxygen species, restored glutathione levels which were reduced in the presence of H(2)O(2), and decreased cell death during H(2)O(2)-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 controlled cortical impact) 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.