Short communicationOptimization of pilocarpine-mediated seizure induction in immunodeficient NodScid mice

- We tested different conditions for generating a TLE model in NodScid mice.
- Multiple 100 mg/kg injections of pilocarpine have been shown to be optimal in inducing TLE in NodScid mice.
- NodScid mice with SE efficiently developed SRS and expressed mossy fiber sprouting.

SummaryTemporal lobe epilepsy (TLE) has been modeled in mice using pilocarpine induction, with variable results depending on specific strains. To allow efficient xenotransplantation for the purpose of optimizing potential cell-based therapy of human TLE, we have determined the optimal dosing strategy to produce spontaneous recurring seizures in immunodeficient NodScid mice. Multiple 100 mg/kg injections of pilocarpine have been shown to be more effective than single 300-400 mg/kg injections for inducing spontaneous seizures in NodScid mice. Under our optimal conditions, 88.1 ± 2.9% of the mice experienced status epilepticus (SE) with a survival rate of 61.8 ± 5.9%. Surviving SE mice displayed spontaneous recurrent seizures at a frequency of 2.8 ± 0.9 seizures/day for a duration of 41.1 ± 3.5 s. The widely used method of a single injection of pilocarpine was significantly less efficient in inducing seizures in NodScid mice. Therefore, we have determined that a multiple injection “ramping up” of 100 mg/kg of pilocarpine is optimal for inducing TLE-like spontaneous seizures in NodScid mice. Using this method, mice with SE efficiently developed SRS and expressed mossy fiber sprouting, a signature histopathological feature of TLE.