Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice

Heather Shibley, Bret N. Smith

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

Abstract

Several rodent models are available to study the cellular mechanisms associated with the development of temporal lobe epilepsy (TLE), but few have been successfully transferred to inbred mouse strains commonly used in genetic mutation studies. We examined spontaneous seizure development and correlative axon sprouting in the dentate gyrus of CD-1 and C57BL/6 mice after systemic injection of pilocarpine. Pilocarpine induced seizures and status epilepticus (SE) after systemic injection in both strains, although SE onset latency was greater for C57BL/6 mice. There were also animals of both strains which did not experience SE after pilocarpine treatment. After a period of normal behavior for several days after the pilocarpine treatment, spontaneous tonic-clonic seizures were observed in most CD-1 mice and all C57BL/6 that survived pilocarpine-induced SE. Robust mossy fiber sprouting into the inner molecular layer was observed after 4-8 weeks in mice from both strains which had experienced SE, and cell loss was apparent in the hippocampus. Mossy fiber sprouting and spontaneous seizures were not observed in mice that did not experience a period of SE. These results indicate that pilocarpine induces spontaneous seizures and mossy fiber sprouting in both CD-1 and C57BL/6 mouse strains. Unlike systemic kainic acid treatment, the pilocarpine model offers a potentially useful tool for studying TLE development in genetically modified mice raised on the C57BL/6 background.

Original languageEnglish
Pages (from-to)109-120
Number of pages12
JournalEpilepsy Research
Volume49
Issue number2
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
We thank S. Misra, R. Winokur for assistance with animal preparation, D. Liu for technical assistance, and Dr S.F. Davis for comments on the manuscript. Thanks also to Dr J. Weber for use of the sliding microtome. This work supported by grants to BNS from the Louisiana Board of Regents LEQSF-RD-A-35, the American Heart Association SDG-0030284N, and the Dean of the College of Liberal Arts and Sciences at Tulane University.

Keywords

  • Dentate gyrus
  • Epilepsy
  • Model
  • Murine
  • Transgenic

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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