Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats

Akihiko Kondo, Tetsuro Shingo, Takao Yasuhara, Satoshi Kuramoto, Masahiro Kameda, Yoichiro Kikuchi, Toshihiro Matsui, Yasuyuki Miyoshi, Takashi Agari, Cesario V. Borlongan, Isao Date

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We explored the effects of exogenous and endogenous erythropoietin (EPO) in a seizure model of rat. Adult male Fischer 344 rats received continuous intraventricular infusion of EPO dissolved in saline containing 1 mg/ml of rat serum albumin, anti-EPO antibody, saline containing 1 mg/ml of rat serum albumin or combined EPO and neuropeptide Y (NPY) Y2-receptor antagonist. Animals were behaviorally evaluated for seizure development over 6 h after kainic acid injection followed by immunohistochemical assays. Mortality rate, seizure severity, apoptotic cell death and abnormal cell proliferation in the hippocampus of EPO-treated epileptic rats were significantly attenuated, compared to control rats. Anti-EPO antibody in non-EPO-treated animals worsened seizures and CA1 neuronal cell death, while NPY Y2-receptor antagonist cancelled the therapeutic effects of exogenous EPO. Both exogenous and endogenous EPO might modulate seizure severity and protect the hippocampal neurons in epileptic rats, via novel mechanistic pathways involving blockade of epileptogenic cell formation coupled with NPY receptor modulation in the hippocampus.

Original languageEnglish
Pages (from-to)127-136
Number of pages10
JournalBrain Research
Volume1296
DOIs
Publication statusPublished - Oct 16 2009

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Neuropeptide Y
Dentate Gyrus
Erythropoietin
Seizures
Up-Regulation
Neuropeptide Y Receptors
Serum Albumin
Anti-Idiotypic Antibodies
Hippocampus
Cell Death
Intraventricular Infusions
Kainic Acid
Inbred F344 Rats
Therapeutic Uses
Cell Proliferation
Neurons
Injections
Mortality

Keywords

  • Apoptosis
  • Cell proliferation
  • Generalized seizure
  • Neuropeptide Y
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats. / Kondo, Akihiko; Shingo, Tetsuro; Yasuhara, Takao; Kuramoto, Satoshi; Kameda, Masahiro; Kikuchi, Yoichiro; Matsui, Toshihiro; Miyoshi, Yasuyuki; Agari, Takashi; Borlongan, Cesario V.; Date, Isao.

In: Brain Research, Vol. 1296, 16.10.2009, p. 127-136.

Research output: Contribution to journalArticle

Kondo, Akihiko ; Shingo, Tetsuro ; Yasuhara, Takao ; Kuramoto, Satoshi ; Kameda, Masahiro ; Kikuchi, Yoichiro ; Matsui, Toshihiro ; Miyoshi, Yasuyuki ; Agari, Takashi ; Borlongan, Cesario V. ; Date, Isao. / Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats. In: Brain Research. 2009 ; Vol. 1296. pp. 127-136.
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