[Age difference of the activation of apoptotic cascade reaction following LiCl-pilocarpine status epilepticus].

OBJECTIVE

To explore the age character of the activity of Caspase 3 and neuron death induced by LiCl-pilocarpine status epilepticus.

METHODS

LiCl-pilocarpine was injected into healthy infant rats (19 days) and adult rats (2-3 months) subcutaneously and intra-abdominally to evoke status epilepticus (SE). First, the age difference of the seizure was used to measure the sensitivity of seizure. Second, the dynamic features of the apoptotic neurons and the activity of Caspase 3 at 15, 30 min and 1, 2, 4, 8 hours after SE respectively were investigated by TUNEL, flow cytometry and fluorospectrophotometry.

RESULTS

(1) The average duration from the injection to seizure was (13.3 +/- 5.63) min in infant rats, and (22.5 +/- 5.66) min in adult rats. (2) The proportion of the 4th or 5th degree of severity at onset of seizure was 68% in infant rats and 18% in adult rats. (3) Although the count of died neurons (in the CA3 of hippocampus, dentate gyrus and cortex of temporal lobe) was physiologically higher in normal infant rats than in adult rats, the count of positive neurons by TUNEL stain in mature brain (524 +/- 26) remarkably increased and exceeded that in premature brain (465 +/- 26) at 30 min after SE. Although continuously observed until 8 hours after SE, the count of apoptotic neurons in mature brain was also remarkably higher than that in infant brain. Change of neurons in apoptotic early events detected by flow cytometry was the same as the result of TUNEL. (4) The increasing proportion of activity of Caspase 3 after SE for 30 min in adult rats remarkably exceeded that in infant rats; it was 0.10 +/- 0.07 in adult rats and 0.003 +/- 0.04 in infant rats. The difference between the infant rats (0.39 +/- 0.20) and adult rats (0.10 +/- 0.20) increased after SE for 2 hours.

CONCLUSION

A mechanism of inhibiting apoptotic process in premature brain during SE for the protection against brain damage was well reconfirmed by different animal SE models induced by lithium-pilocarpine. It was indicated that the protective mechanism against brain damage in premature brain could be presented in most severe seizures of different types. This protective mechanism could act on the apoptotic occurrence in the earlier period before the activation of Caspase cascade reaction.