Regional Calcium Accumulation and Cation Shifts in Rat Brain by Kainate

Abstract: Following local application of kainic acid, changes in the contents of Na⁺, K⁺, Ca²⁺, and Mg²⁺ of the striatum, cerebellum, and hippocampus of the rat were observed at various times after surgery. Within 1 h the levels of K⁺ decreased 20% whereas the levels of Na⁺ and Ca²⁺ increased at least 50% and 20%, respectively. These changes persisted for more than 8 weeks. Ca²⁺ levels rose further, to more than 10-fold during 8 weeks. The Mg²⁺ levels were slightly and only transiently decreased. Unilateral injections of kainate into the striatum affected the contents of these cations not only in this area, but also in the overlying cerebral cortex, the olfactory tubercle, and the ipsilateral substantia nigra. The Ca²⁺ increases were less when rats were kept on a diet deficient in Ca²⁺ and vitamin D. ⁴⁵Ca²⁺, intravenously administered, accumulated significantly more in the kainate-lesioned striatum and substantia nigra than in the homotopic contralateral areas. Electron microscopic examination of the localization of Ca²⁺ with the oxalate-pyroantimonate technique showed the appearance of extracellularly located deposits and the accumulation of Ca²⁺ in (possibly degenerating) myelinated axons in kainate-lesioned striata. This study provides evidence that calcification of cerebral tissue is closely associated with neurodegenerative processes and shows that kainate may serve as a tool to elucidate the mechanism of brain calcification. The results are discussed in relation to idiopathic calcinosis (striopallidodentate calcinosis, Fahr's disease).