Effect of metal chelating agents on the direct and seizure-related neuronal death induced by zinc and kainic acid.

ABSTRACT

The ability of metal chelating agents to affect seizure-induced neuronal death caused by intra-amygdaloid injections of kainic acid was investigated. N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), diethyldithiocarbamate (DEDTC) and diphenylthiocarbazone (dithizone), administered simultaneously or within 30 min of a kainate injection, all failed to affect the amount of neuronal loss in the ipsilateral hippocampus. This failure was not due to an inability to complex endogenous 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) although it lasted for 8 h with TPEN. TPEN, but not DEDTC or dithizone prevented the neuronal loss caused by intra-hippocampal injections of zinc chloride. In the presence of diazepam to prevent seizures, co-injection of TPEN and kainate into the hippocampus also failed to prevent the direct cytotoxicity of kainate. Endogenous zinc, released from mossy fibres in the hippocampus by seizure activity, does not appear to modify seizure activity sufficiently to alter the extent of the resulting neuronal death.