Regional brain glucose utilization following intrastriatal injections of kainic acid

Abstract

Regional brain glucose utilization following intrastriatal injections of kainic acid (KA) was studied by [14C]deoxyglucose autoradiography. In halothane anesthetized rats intrastriatal injections of 0.5-1.9 nmol KA produced histological lesions characterized by neuronal necrosis and glial reaction which varied in volume from approximately 3 to 25 cu. mm. These lesions were restricted to the striatal injection site. Intrastriatal injections of 3.8 nmol led to large lesions in striatum but also in ipsilateral hippocampus, pyriform cortex, entorhinal cortex, and amygdaloid nuclei. Injection doses of 0.5-3.8 nmol KA produced a large increase in striatal glucose utilization within 1 h; 7 days after injections however, glucose utilization was reduced below control levels in a dose-dependent manner. In addition to striatum there were large transient increases in glucose utilization in deep layers of frontal cortex, substantia nigra pars reticulata, ventral tier nuclei of thalamus, and lateral septum. Each of these structures bear close physical or synaptic proximity to the striatal injection site. Also, structures far distant from the striatal injection site exhibited large, transient, dose-dependent increases in glucose utilization; these regions included hippocampus, pyriform cortex, entorhinal cortex, and amygdaloid nuclei. There was a close correlation between the development of areas of neuronal necrosis and a reduction in glucose utilization. These results suggest that intrastriatal injections of KA may cause metabolic and perhaps electrical activation not only of structures near or synaptically connected to the injection site, but also of far distant, but particularly 'sensitive' brain structures probably by diffusion of small amounts of drug. The occurrence of neuronal death in limbic structures after injections of relatively high doses of KA into striatum may result from prolonged firing in those circuits which continues without the prolonged presence of KA.