Methods for inducing neuronal loss in preweanling rats using intracerebroventricular infusion of kainic acid

Abstract

Excitotoxins, such as kainic acid (KA), have been shown to produce neuronal degeneration in the adult rat brain. While preweanling rats have been shown to be relatively resistant to the neurotoxicity of lower doses of KA, the presence of neuronal loss at higher doses (of KA) has only begun to be investigated in such animals. A reliable method of producing neuronal loss in preweanling rats is to administer nmol concentrations of KA via intracerebroventricular (i.c.v.) injections on postnatal day 7 (P7). Using a three-dimensional, non-biased cell counting technique, we have shown that neuronal loss is observed in the CA3 subfield of the hippocampal formation at P45 and P75. Further, immunohistochemical studies of markers for cell death may be useful to examine the types of cellular processes associated with such neuronal loss. Data from our own experiments suggest the activation of immediate–early genes in the neuronal loss produced by KA administration at P7. This developmental animal model of neuronal loss may be useful in studying neurodevelopmental disorders where the onset of symptoms or cognitive deficits is thought to follow an early developmental insult.