Early transplantation of an encapsulated glial cell line-derived neurotrophic factor-producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease

Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Kazuki Kobayashi, Akira Takeuchi, Akimasa Yano, Yuan Wenji, Masahiro Kameda, Toshihiro Matsui, Yasuyuki Miyoshi, Isao Date

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Object. Glial cell line-derived neurotrophic factor (GDNF) has been shown to confer neuroprotective effects on dopaminergic neurons. The authors investigated the effects of GDNF on 6-hydroxydopamine (6-OHDA)-treated dopaminergic neurons in vitro and in vivo. Methods. First, the authors examined how 1, 10, or 100 ng/ml of GDNF, administered to cells 24 hours before, simultaneously with, or 2 or 4 hours after 6-OHDA was added, affected dopaminergic neurons. In a primary culture of E14 murine ventral mesencephalic neurons, earlier treatment with the higher dosage of GDNF suppressed 6-OHDA-induced loss of dopaminergic neurons better than later treatment. Next, the authors examined whether continuous infusion of GDNF at earlier time points would demonstrate a greater neuroprotective effect in a rat model of Parkinson disease (PD). They established a human GDNF-secreting cell line, called BHK-GDNF, and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally implanted into the striatum of adult rats 1 week before; simultaneously with; or 1, 2, or 4 weeks after 6-OHDA was given to induce lesions of the same striatum. With the earlier transplantation of a BHK-GDNF capsule, there was a significant reduction in the number of amphetamine-induced rotations displayed by the animals. Rats that had received earlier implantation of BHK-GDNF capsules displayed more tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and a tendency for glial proliferation in the striatum. Conclusions. These neuroprotective effects may be related to glial proliferation and signaling via the GDNF receptor a1. The results of this study support a role for this grafting technique in the treatment of PD.

Original languageEnglish
Pages (from-to)80-89
Number of pages10
JournalJournal of neurosurgery
Volume102
Issue number1
DOIs
Publication statusPublished - Jan 2005

Keywords

  • Dopaminergic neuron
  • Encapsulation
  • Glial cell line-derived neurotrophic factor
  • Glial cell line-derived neurotrophic factor receptor-α1
  • Neuroprotection
  • Parkinson disease
  • Rat

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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