alpha-Phenyl-N-tert-butylnitrone attenuates excitotoxicity in rat striatum by preventing hydroxyl radical accumulation.
Various in vitro experiments have indicated that oxygen-derived free radicals may contribute to excitotoxic neuronal death. In the present study we induced excitotoxicity in rat striatum by perfusing glutamate at a high concentration through a microdialysis probe. We observed an increased formation of hydroxyl radicals (.OH) during the perfusion of the excitotoxin and an extensive striatal lesion 24 h after the insult. The spin trap, alpha-phenyl-N-tert-butylnitrone (PBN), attenuated both hydroxyl radical levels and the volume of the lesion. This result suggests that the neuroprotection may be due to a free radical scavenging mechanism. It also implies that PBN may be used in pathological situations involving excitotoxicity such as stroke, brain trauma, and chronic neurologic diseases.
Lancelot
E
E
Laboratoire de Pharmacologie, Université Descartes, Paris France.
Revaud
M L
ML
Boulu
R G
RG
Plotkine
M
M
Callebert
J
J
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D003497:Cyclic N-Oxides; D018846:Excitatory Amino Acids / Q000633:toxicity*; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D008297:Male; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels
D003497:Cyclic N-Oxides; D018846:Excitatory Amino Acids; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D013113:Spin Labels; D017665:Hydroxyl Radical; C029217:phenyl-N-tert-butylnitrone