NEUROPROTECTIVE EFFECT OF FREE-RADICAL SCAVENGERS ON BETA-N-OXALYLAMINO-L-ALANINE (BOAA)-INDUCED NEURONAL DAMAGE IN RAT HIPPOCAMPUS

The neurotoxin beta-N-oxalylamino-L-alanine (BOAA), found in Lathyrus sativus seeds, is thought to be the causative agent of neurolathyrism. We have investigated the neuroprotective effects of free radical scav engers on BOAA-induced toxicity following focal injection (1 mu l) of BOAA and comparing the pathological outcome with the effects of inject ions of ha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kai nate (KA) or N-methyl-D-aspartate (NMDA) into the dorsal hippocampus o f male Wistar rats. Cellular damage was assessed histologically. BOAA (50 nmol) induced a highly selective pattern of hippocampal damage ide ntical with that seen with AMPA (1 nmol). BOAA-induced neurotoxicity, but not AMPA, KA (0.5 nmol) or NMDA (25 nmol)-induced neurotoxicity, w as prevented in a dose-dependent manner by focal co-injection of four potential free radical scavengers; dimethyl sulphoxide (DMSO) (1750-70 00 nmol), dimethylthiourea (DMTU) (8000 nmol), dimethylformamide (DMF) (7000 nmol) and mannitol(1000 nmol). These findings suggest that hipp ocampal damage induced by BOAA involves an interaction between AMPA re ceptors and free radicals.