+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      The metabotropic glutamate receptor system protects against ischemic free radical programmed cell death in rat brain endothelial cells.

      Journal of Cerebral Blood Flow & Metabolism

      metabolism, Receptors, Metabotropic Glutamate, Rats, Sprague-Dawley, Rats, Phosphatidylserines, biosynthesis, Nitric Oxide, In Situ Nick-End Labeling, pathology, Hypoxia-Ischemia, Brain, Free Radicals, physiology, Enzyme Activation, enzymology, Endothelium, Vascular, DNA Fragmentation, Cysteine Endopeptidases, Cell Membrane, Caspases, Caspase 3, Caspase 1, blood supply, Brain, Apoptosis, Animals

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          As one of the key determinants of ischemic injury, cerebrovascular endothelial cell (EC) degeneration may be dependent upon the generation of the free radical nitric oxide (NO) and the subsequent induction of programmed cell death (PCD). Although the mechanisms that can prevent EC injury are most likely multifactorial in origin, the metabotropic glutamate receptor (mGluR) system may represent a novel therapeutic approach for ECs given the ability of the mGluR system to reverse neuronal cell injury. This study examined the modulation of individual subtypes of mGluRs during anoxia and NO toxicity in primary rat cerebrovascular ECs. Cell injury was determined through trypan blue dye exclusion, intracellular lactate dehydrogenase release, DNA fragmentation, membrane phosphatidylserine (PS) exposure, and cysteine protease activity. Anoxia, through the generation of NO, and exposure to exogenous NO were directly toxic to ECs. Exposure to NO rapidly decreased EC viability from 98% +/- 2% to 40% +/- 9%, increased DNA fragmentation from 2% +/- 2% to 61% +/- 9%, and increased membrane PS exposure from 3% +/- 3% to 66% +/- 6% over a 24-hour period. Activation of the mGluR system significantly increased EC survival through the prevention of NO-induced DNA fragmentation and cellular membrane PS residue exposure. In contrast, antagonism of the mGluR system failed to prevent PCD. Cytoprotection by the mGluR system was dependent, at least in part, upon the direct inhibition of NO-generated caspase 1- and caspase 3-like activities. Further investigation into the ability of the mGluR system to prevent PCD in ECs may open new therapeutic avenues for the treatment of cerebrovascular injury.

          Related collections

          Author and article information



          Comment on this article