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, -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.