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)-O-.) during the perfusion of the excitotoxin and an extensive striatal lesion 24 h after the insult. The spin trap, alpha-phenyl-N-tert-butylnitrone (PEN), 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 PEN may be used in pathological situations involving excitotoxicity such as stroke, brain trauma, and chronic neurologic diseases. (C) 1997 Elsevier Science Inc.