The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model

Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Yuan Wen Ji, Masahiro Kameda, Akira Takeuchi, Akimasa Yano, Shinsaku Nishio, Toshihiro Matsui, Yasuyuki Miyoshi, Hirofumi Hamada, Isao Date

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects on dopaminergic (DA) neurons. In this study, we investigated whether the effects of VEGF were dose-dependent or not. First, VEGF was shown to be neuroprotective on 6-hydroxydopamine (6-OHDA)-treated murine DA neurons in vitro, although the 1 ng/ml of VEGF displayed more neuroprotective effects than 100 ng/ml. Furthermore, using 2 sizes of capsules (small/large) with different secreting quantities, 6-OHDA-treated rats receiving the small capsule filled with VEGF-secreting cells (BHK-VEGF) into the striatum showed a significant decrease in amphetamine-induced rotational behavior in number and a significant preservation of TH-positive fibers compared to those receiving the large BHK-VEGF capsule as well as those receiving BHK-Control capsule. Rats receiving the large BHK-VEGF capsule showed much more glial proliferation, angiogenesis, and brain edema around the capsule than those with the small one. High-dose administration of VEGF might cause poor circulation related to brain edema, although low-dose administration of VEGF displays neuroprotective effects on DA neurons. Our results demonstrate the importance of administration dose of VEGF, suggesting that low-dose administration of VEGF might be desirable for Parkinson's disease.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBrain Research
Volume1038
Issue number1
DOIs
Publication statusPublished - Mar 15 2005

Keywords

  • Angiogenesis
  • Brain edema
  • Encapsulation
  • Glial proliferation
  • Neuroprotection
  • VEGF

ASJC Scopus subject areas

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

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