Study on the long-term change of calcium homeostasis and kinetics in chronic epilepsy model / 中华神经科杂志

ABSTRACT

Objective To study the role of calcium homeostatic and kinetics in the epileptogenesis activity. Methods Hippocampal neurons were acutely isolated from controls and status epilepticus (SE) models induced by lithium-pilocarpine at different time point. The [Ca2+]i levels were detected by laser scanning confocal microscope. And the ability to restore resting [Ca2+]i levels after a brief exposure to 5 μmol/L glutamate in control and epileptic neurons were evaluated. Results The [Ca2+]i level of acute separated hippocampal neurons in the control rats was (95.4±22. 1) nmol/L After injection of lithium pilocarpine, the [Ca2+]i level in hippecampal neurons increased dramatically to (867.6±35.2) nmol/L, and decreased to (292.8 ± 18.3) nmol/L on the 7th day, lasting for about 30 days ((220. 8± 17.6) nmol/L), it is higher than that in the control group (t = 12. 55, P < 0.01). The distribution of neuronal [Ca22+]i showed that 92% of control neurons were in the normal range of [Ca2+]i level (25-150 nmol/L) ; After 6 hours, however [Ca2+]i levels of all SE neurons increased, and 85% of which were higher than 500 nmol/L; After 7, 14 and 30 days, there were 75%, 60% and 52% of SE neurons still manifested an elevated [Ca22+]i level, but less than 500 nmol/L. After the exposure to 5 μmol/L glutamate treatment for 2 minutes, [Ca2+]i of the control neurons restored to baseline values in (9. 5±3.4) minutes, whereas the SE rats of acute, latent and chronic phases did not (t = 5.08, 4. 56, 4. 21, all P < 0. 01). Conclusion Lithium-pilocarpine induced epilepsy causes a long-term alteration of calcium homeostatic mechanisms of hippocampus neurons, which may play an important role in the development and maintenance of spontaneous recurrent seizures.