To determine the extent and time course of local and distant neuronal damage produced by microiontophoretic administration of kainic acid (KA) into the central amygdaloid nucleus, distribution of neuronal damage was compared in various brain areas after different survival times. For demonstration of damaged, so-called 'dark' neurons, a newly developed silver stain was employed. In addition, silver staining method was used to visualize microglia cells. In a separate experiment, electroencephalographic (EEG) activity was recorded from the amygdaloid body, hippocampus, and the frontal cortex before and after microiontophoretic KA lesion of the central amygdaloid nucleus. It was observed that (1) even a minute amount of KA into this nucleus caused transient neuronal damage in distant brain areas; (2) the hippocampal formation, subiculum, entorhinal cortex, piriform cortex, and lateral septum were consistently affected; (3) the extent and time course of neuronal damage and appearance of microglia cells varied from area to area; (4) the KA neurotoxicity in distant brain areas appeared to depend on specific excitatory circuits, especially in the hippocampal formation; (5) the appearance and time course of pathologic EEG activity paralleled the appearance of dark neurons; and (6) the absence of pathologic EEG activity and the lack of massive neuronal loss or microglia proliferation in distant brain areas of rats surviving longer than 48 h suggested that these areas may have recovered both morphologically end functionally. Although details of cellular mechanism responsible for development of 'dark' degeneration of neurons are not known, the silver method employed in the present study proved to be a sensitive, useful tool for fine histological analyses of early and distant consequences of excitotoxic lesions.
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