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GDNF-pretreatment enhances the survival of neural stem cells following transplantation in a rat model of Parkinson's disease.

Abstract
Cell transplantation has been shown to be an effective therapy for central nervous system disorders in animal models. Improving the efficacy of cell transplantation depends critically on improving grafted cell survival. We investigated whether glial cell line-derived neurotrophic factor (GDNF)-pretreatment of neural stem cells (NSCs) enhanced grafted cell survival in a rat model of Parkinson's disease (PD). We first examined the neuroprotective effects of GDNF on oxygen-glucose deprivation (OGD) in NSCs. Cells were pretreated with GDNF for 3 days before subjecting them to OGD. After 12h of OGD, GDNF-pretreated NSCs showed significant increases in survival rates compared with PBS-pretreated NSCs. An apoptosis assay showed that the number of apoptotic cells was significantly decreased in GDNF-pretreated NSCs at 1h and 6h after OGD. A PD rat model was then established by unilateral injection of 6-hydroxydopamine (6-OHDA, 9μg) into the medial forebrain bundle. Two weeks after 6-OHDA injection, GDNF-pretreated NSCs, PBS-pretreated NSCs, or PBS were injected into PD rat striatum. The survival of grafted cells in the striatum was significantly increased in the GDNF-pretreated NSC group compared with the control groups. GDNF pretreatment increased survival of NSCs following transplantation, at least partly through suppression of cell apoptosis.
AuthorsF Wang, M Kameda, T Yasuhara, N Tajiri, Y Kikuchi, H B Liang, J T Tayra, A Shinko, T Wakamori, T Agari, I Date
JournalNeuroscience research (Neurosci Res) Vol. 71 Issue 1 Pg. 92-8 (Sep 2011) ISSN: 1872-8111 [Electronic] Ireland
PMID21699926 (Publication Type: Journal Article)
CopyrightCopyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
Chemical References
  • Glial Cell Line-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Neurotoxins
  • Oxidopamine
Topics
  • Animals
  • Cell Survival (drug effects, physiology)
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Glial Cell Line-Derived Neurotrophic Factor (pharmacology, physiology)
  • Graft Survival (drug effects, physiology)
  • Mice
  • Mice, Inbred ICR
  • Neural Stem Cells (drug effects, physiology, transplantation)
  • Neuroprotective Agents (pharmacology)
  • Neurotoxins (toxicity)
  • Oxidopamine (toxicity)
  • Parkinsonian Disorders (chemically induced, physiopathology, surgery)
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation (methods)
  • Transplantation, Heterologous (methods)

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