Abstract
Determining the minimal duration of status epilepticus (SE) that leads to the development of subsequent spontaneous seizures (i.e., epilepsy) is important, because it provides a critical time-window for seizure intervention and epilepsy prevention. In the present study, male ICR (Imprinting Control Region) mice were injected with pilocarpine to induce acute seizures. SE was terminated by diazepam at 10 min, 30 min, 1 h, 2 h and 4 h after seizure onset. Spontaneous seizures occurred in the 1, 2 and 4 h SE groups, and the seizure frequency increased with the prolongation of SE. Similarly, the Morris water maze revealed that the escape latency was significantly increased and the number of target quadrant crossings was markedly decreased in the 1, 2 and 4 h SE groups. Robust mossy fiber sprouting was observed in these groups, but not in the 10 or 30 min group. In contrast, Fluoro-Jade B staining revealed significant cell death only in the 4 h SE group. The incidence and frequency of spontaneous seizures were correlated with Timm score (P = 0.004) and escape latency (P = 0.004). These data suggest that SE longer than one hour results in spontaneous motor seizures and memory deficits, and spontaneous seizures are likely associated with robust mossy fiber sprouting but not neuronal death.