title: 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.
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Leung
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: George
authors.initials: G
authors.lastname: Savvidis
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Yeachan
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Iskandar
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Luna
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Miles
authors.initials: M
authors.lastname: Cunningham
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: schung@mclean.harvard.edu.
authors.forename: Sangmi
authors.initials: S
authors.lastname: Chung
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D016513:Mice, SCID; D019599:Mossy Fibers, Hippocampal / Q000473:pathology / Q000503:physiopathology; D010862:Pilocarpine; D013226:Status Epilepticus / Q000473:pathology / Q000503:physiopathology; D014741:Video Recording
chemical_list: D010862:Pilocarpine
keywords: Mossy fiber sprouting; NodScid mice; Pilocarpine; Seizure; Temporal lobe epilepsy