One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death
1Department of Pharmacology, College of Medicine, Zhejiang University, Hangzhou 310058, China
2Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China
Abstract
Determining the minimal duration of status epilepticus (SE) that leads to the development of subsequentspontaneous seizures (i.e., epilepsy) is important,
because it provides a critical time-window for seizureintervention 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.
Keywords
epileptogenesis; pilocarpine; Fluoro-Jade B staining; Timm staining; Morris water maze