Age- and region-dependent patterns of Ca2+ accumulations following status epilepticus

Elevated Ca(2+) concentrations have been implicated in cell death mechanisms following seizures, however, the age and brain region of intracellular Ca(2+) accumulations [Ca(2+)](i), may influence whether or not they are toxic. Therefore, we examined regional accumulations of (45)Ca(2+) by autoradiography from rats of several developmental stages (P14, P21, P30 and P60) at 5, 14, and 24h after status epilepticus. To determine whether the uptake was intracellular, Ca(2+) was also assessed in hippocampal slices with the dye indicator, Fura 2AM at P14. Control animals accumulated low homogeneous levels of (45)Ca(2+); however, highly specific and age-dependent patterns of (45)Ca(2+) uptake were observed at 5h. (45)Ca(2+) accumulations were predominant in dorsal hippocampal regions, CA1/CA2/CA3a, in P14 and P21 rats and in CA3a and CA3c neurons of P30 and P60 rats. Selective midline and amygdala nuclei were marked at P14 but not at P21 and limbic accumulations recurred with maturation that were extensive at P30 and even more so at P60. At 14 h, P14 and P21 rats had no persistent accumulations whereas P30 and P60 rats showed persistent uptake patterns within selective amygdala, thalamic and hypothalamic nuclei, and other limbic cortical regions that continued to differ at these ages. For example, piriform cortex accumulation was highest at P60. Fura 2AM imaging at P14 confirmed that Ca(2+) rises were intracellular and occurred in both vulnerable and invulnerable regions of the hippocampus, such as CA2 pyramidal and dentate granule cells. Silver impregnation showed predominant CA1 injury at P20 and P30 but CA3 injury at P60 whereas little or no injury was found in extrahippocampal structures at P14 and P20 but was modest at P30 and maximal at P60. Thus, at young ages there was an apparent dissociation between high (45)Ca(2+) accumulations and neurotoxicity whereas in adults a closer relationship was observed, particularly in the extrahippocampal structures.