Optimization of pilocarpine-mediated seizure induction in immunodeficient Nod-Scid mice

Autor: Sandra Ahn, Kwang-Soo Kim, Sangmi Chung, Amanda Leung, Yeachan Kim, George Savvidis, Maria Jose Luna, Miles G. Cunningham, Danielle Iskandar
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Popis: Temporal 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 sec. 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.
Databáze: OpenAIRE