SEIZURES AND SELECTIVE CA-1 HIPPOCAMPAL-LESIONS INDUCED BY AN EXCITOTOXIC CYANIDE METABOLITE, 2-IMINOTHIAZOLIDINE-4-CARBOXYLIC ACID

Excitatory amino acid (EAA)-like and excitotoxic properties of the sec ondary metabolite of cyanide, 2-iminothiazolidine-4-carboxylic acid, ( 2-ICA) were evaluated because of its possible role in cyanide-induced neurotoxicity. Intracerebroventricular (i.c.v.) injections of 2-ICA in mice produced wild-running seizures that were qualitatively and quant itatively similar to seizures observed with glutamate. 2-ICA, kainate and proline seizures were prevented by both the NMDA and non-NMDA anta gonists, MK-801 and CNQX, respectively. In contrast, NMDA-induced seiz ures were prevented by MK-801, but not CNQX. When infused i.c.v. in ra ts over a seven day period, 2-ICA produced extensive and selective los s of CA-1 pyramidal neurons of the hippocampus. In hippocampal slices preloaded with D-[H-3]aspartate, 2-ICA superfusion did not evoke relea se nor significantly augment potassium stimulated release of the radio labeled transmitter. These findings indicate 2-ICA has excitotoxic pro perties and its role in cyanide neurotoxicity deserves further study. (C) 1995 Intox Press, Inc.