Optimization of pilocarpine-mediated seizure induction in immunodeficient NodScid mice.

Abstract:

: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 100mg/kg injections of pilocarpine have been shown to be more effective than single 300-400mg/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 ± 3.5s. 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 100mg/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.

journal_name

Epilepsy Res

journal_title

Epilepsy research

authors

Leung A,Ahn S,Savvidis G,Kim Y,Iskandar D,Luna MJ,Kim KS,Cunningham M,Chung S

doi

10.1016/j.eplepsyres.2014.10.016

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

114-8

eissn

0920-1211

issn

1872-6844

pii

S0920-1211(14)00295-2

journal_volume

109

pub_type

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