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

International Journal of Developmental Neuroscience - Tập 26 - Trang 779-790 - 2008
Linda K. Friedman1,2, Aleksandr Saghyan1, Alex Peinado3, Robert Keesey2
1Department of Neuroscience, New York College of Osteopathic Medicine, Northern Boulevard, Old Westbury, NY 11581, United States
2Seton Hall University/NJ Neuroscience Institute, South Orange, NJ 07079, United States
3Downstate Medical Center, Brooklyn, NY, United States

Tóm tắt

AbstractElevated Ca2+ concentrations have been implicated in cell death mechanisms following seizures, however, the age and brain region of intracellular Ca2+ accumulations [Ca2+]i, may influence whether or not they are toxic. Therefore, we examined regional accumulations of 45Ca2+ by autoradiography from rats of several developmental stages (P14, P21, P30 and P60) at 5, 14, and 24 h after status epilepticus. To determine whether the uptake was intracellular, Ca2+ was also assessed in hippocampal slices with the dye indicator, Fura 2AM at P14. Control animals accumulated low homogeneous levels of 45Ca2+; however, highly specific and age‐dependent patterns of 45Ca2+ uptake were observed at 5 h. 45Ca2+ 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 Ca2+ 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 45Ca2+ accumulations and neurotoxicity whereas in adults a closer relationship was observed, particularly in the extrahippocampal structures.

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