Tonic-clonic seizures induce division of neuronal progenitor cells with concomitant changes in expression of neurotrophic factors in the brain of pilocarpine-treated mice

Hideo Hagihara, Mizumi Hara, Kyouko Tsunekawa, Yukinori Nakagawa, Makoto Sawada, Kiwao Nakano

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Epileptic seizures cause severe and long-lasting events on the architecture of the brain, including neuronal cell death, accompanied neurogenesis, reactive gliosis, and mossy fiber sprouting. However, it remains uncertain whether these functional and anatomical alterations are associated with the development of hyperexcitability, or as inhibitory processes. Neurotrophic factors are probable mediators of these pathophysiological events. The present study was designed to clarify the role of various neurotrophic factors on the pilocarpine model of seizures. At 4 h following pilocarpine-induced seizures, expression of NGF, BDNF, HB-EGF, and FGF-2 increased only in the mice manifesting tonic-clonic convulsions and not in mice without seizures. NT-3 expression decreased in pilocarpine-treated mice experiencing seizures, tonic-clonic or not, compared to mice with no seizures. Neuronal cell damage, which was evident by Fluoro-Jade B staining, was observed within 24 h in the mice exhibiting tonic-clonic seizures, followed by an increase in the number of BrdU-positive cells and glial cells, which were evident after 2 days. None of these pathophysiological changes occurred in the mice which showed no seizures, although they were injected with pilocarpine, nor in the activated epilepsy-prone EL mice, which experienced repeated severe seizures. Together, these results suggest that neuronal damage occurring in the brain of the mice manifesting tonic-clonic seizures is accompanied by neurogenesis. This sequence of events may be regulated through changes in expression of neurotrophic factors such as NGF, BDNF, HB-FGF, and NT-3.

Original languageEnglish
Pages (from-to)258-266
Number of pages9
JournalMolecular Brain Research
Volume139
Issue number2
DOIs
Publication statusPublished - 03-10-2005

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Pilocarpine
Nerve Growth Factors
Seizures
Stem Cells
Brain
Brain-Derived Neurotrophic Factor
Neurogenesis
Nerve Growth Factor
Epilepsy
Tonic-Clonic Epilepsy
Gliosis
Fibroblast Growth Factor 2
Bromodeoxyuridine
Neuroglia
Cell Death
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

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Tonic-clonic seizures induce division of neuronal progenitor cells with concomitant changes in expression of neurotrophic factors in the brain of pilocarpine-treated mice. / Hagihara, Hideo; Hara, Mizumi; Tsunekawa, Kyouko; Nakagawa, Yukinori; Sawada, Makoto; Nakano, Kiwao.

In: Molecular Brain Research, Vol. 139, No. 2, 03.10.2005, p. 258-266.

Research output: Contribution to journalArticle

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