The Free Radical Trapping Agent N-<i>Tert</i>.-Butyl-α-Phenylnitrone (PBN) Attenuates Cerebral Ischaemic Injury in Gerbils

Abstract

Several studies have suggested that oxygen-derived free radicals play an important role in the genesis of ischaemia-induced neuronal damage. We report here that the spin trap agent, N-tert.-butyl-alpha-phenylnitrone (PBN) reduced neuronal damage in gerbils subjected to forebrain ischaemia. PBN (100 mg/kg) administered either 30 min. prior to, or 30 min. after a 5 min. period of bilateral carotid occlusion prevented the increase in locomotor activity observed in saline-injected ischaemic animals and significantly reduced the damage to the hippocampal CAI pyramidal cell layer observed 5 days post-ischaemia. Telemetry measurements of body temperature revealed that administration of PBN and the induction of cerebral ischaemia were associated with small reductions in body temperature, but these changes were not significant. PBN (100 mg/kg) administered 2 hr post-ischaemia failed to protect against cerebral ischaemia. These findings support the hypothesis of an involvement of free radicals in ischaemia-reperfusion induced cerebral damage and suggest that spin trap agents may be useful for the prevention of cerebral ischaemic damage.