EFFECT OF METAL CHELATING-AGENTS ON THE DIRECT AND SEIZURE-RELATED NEURONAL DEATH INDUCED BY ZINC AND KAINIC ACID

The ability of metal chelating agents to affect seizure-induced neuron al death caused by intra-amygdaloid injections of kainic acid was inve stigated. N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), d iethyldithiocarbamate (DEDTC) and diphenylthiocarbazone (dithizone), a dministered simultaneously or within 30 min of a kainate injection, al l failed to affect the amount of neuronal loss in the ipsilateral hipp ocampus. This failure was not due to an inability to complex endogenou s zinc as all these chelating agents quenched staining for endogenous zinc by the Timm method. However, the period for which this quenching occurred was short for DEDTC and dithizone (a maximum of 1.5 h) althou gh it lasted for 8 h with TPEN. TPEN, but not DEDTC or dithizone preve nted the neuronal loss caused by intra-hippocampal injections of zinc chloride. In the presence of diazepam to prevent seizures, co-injectio n of TPEN and kainate into the hippocampus also failed to prevent the direct cytotoxicity of kainate. Endogenous zinc, released from mossy f ibres in the hippocampus by seizure activity, does not appear to modif y seizure activity sufficiently to alter the extent of the resulting n euronal death. (C) 1998 Elsevier Science B.V. All rights reserved.