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).

Characterization of striatal lesions produced by glutamate uptake alteration: Cell death, reactive gliosis, and changes in GLT1 and GADD45 mRNA expression

“…The analyses by X-ray and electron microscopy have shown that Alizarine Red-stained precipitates are largely composed of calcium and phosphate in the form of hydroxyapatite (Herrmann et al, 1998;Mahy et al, 1995Mahy et al, , 1999; small (around 2 µm mean diameter) and medium (around 4 µm mean diameter) sized deposits can be observed intracellularly whereas the larger ones (around 21 µm diameter), that have psammon body-like appearance, are extracellular (Mahy et al, , 1999. This calcium deposition has been reported to be an excitotoxin-and area-selective mechanism with a progressive character: the deposits growing in size and number at long term after excitotoxin injection (Herrmann et al, 1998;Korf and Postema, 1984;Mahy et al, 1995;Nitsch and Schaefer, 1990;Saura et al, 1995). Regional differences in the formation of calcium deposits have been related to local differences in glial compensatory mechanisms or to differences in calcium buffering and storage; for instance development of calcium concretions has been associated with predominant microglial reaction and lack of such deposits with astrogliosis and tissue atrophy (Saura et al, 1995).…”

Intracellular calcium as an index of neurotoxic damage

“…Whether calcium influx is a direct cause of, or a secondary result of cell death in the nervous system remains a matter of controversy [7][8][9]. Nonetheless, there is good evidence that the calcium influx following repetitive hippocampal stimulation by chemical or electrical means, is the event that leads to regional necrosis [10,11]. In cerebellar slices, the neurotoxicity of excitatory amino acid agonists can be dependent on calcium concentration [12].…”

Intracellular calcium and neurotoxic events

“…However, calcium influx may accompany toxic effects in nerve cells without necessarily being the cause of cell death. Thus, the accumulation of insoluble calcium deposits is associated with many types of neurological damage including seizures (23), spinal cord injury (5), uremia (2), aluminum encephalopathy (20), lead poisoning (53), and kainic acid treatment (33). In any event, [Ca 2 +]; can often serve as an effective indicator of imminent cell death (15).…”