Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson's disease

Takao Yasuhara, Tetsuro Shingo, Kazuki Kobayashi, Akira Takeuchi, Akimasa Yano, Kenichiro Muraoka, Toshihiro Matsui, Yasuyuki Miyoshi, Hirofumi Hamada, Isao Date

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158 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects following ischemia, suggesting that VEGF may potentially be applied as a neuroprotective agent for the treatment of other neurological diseases. In this study, we investigated the neuroprotective capacity of VEGF in a model of Parkinson's disease. VEGF was found to be neuroprotective against cell death of primary E14 murine ventral mesencephalic neurons induced by 6-hydroxydopamine (6-OHDA) treatment in vitro. Further, rats receiving a continuous infusion of VEGF into the striatum via encapsulated hVEGF-secreting cells (baby hamster kidney-VEGF) displayed a significant decrease in amphetamine-induced rotational behavior and a significant preservation of tyrosine hydroxylase-positive neurons and fibers compared with control animals. VEGF likely functions via direct mechanisms by signaling through the neuropilin receptor expressed upon dopaminergic neurons in response to 6-OHDA treatment. Further, VEGF is likely to promote neuroprotection indirectly by activating the proliferation of glia and by promoting angiogenesis. Our results support a potential neuroprotective role for VEGF in the treatment of Parkinson's disease.

Original languageEnglish
Pages (from-to)1494-1504
Number of pages11
JournalEuropean Journal of Neuroscience
Volume19
Issue number6
DOIs
Publication statusPublished - Mar 1 2004

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Keywords

  • Apoptosis
  • Encapsulation
  • Neuropilin
  • Neuroprotection
  • Semaphorin

ASJC Scopus subject areas

  • Neuroscience(all)

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