Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro.
The concept of the neurovascular unit suggests that to be successful, stroke therapies must protect all neuronal, glial and endothelial components in brain. In this study, we tested the efficacy of the free radical scavenger edaravone in three cellular models of oxidative stress. HT22 neuronal cells were subjected to oxidative stress using the standard glutamate-induced glutathione depletion model. Primary rat astrocytes were exposed to H(2)O(2). Oxidative stress was induced in human brain endothelial cells with sodium nitroprusside (SNP). Edaravone significantly reduced oxidative cell death in both HT22 neuronal cells and primary rat astrocytes in a dose-dependent manner. SNP did not kill brain endothelial cells but instead reduced their production of brain-derived neurotrophic factor (BDNF). Edaravone significantly ameliorated this response. These data suggest that free radical scavengers are effective in all cell types of the neurovascular unit, and should still be considered as a potential therapeutic approach for stroke.
Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Brian J
BJ
Lee
Yasuhiro
Y
Egi
Klaus
K
van Leyen
Eng H
EH
Lo
Ken
K
Arai
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D042783:Endothelial Cells / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D000077553:Edaravone; D000983:Antipyrine