title: The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model.
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.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine Dentistry, 2-5-1, Shikata-cho, Okayama 700-8558, Japan. tyasu37@cc.okayama-u.ac.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Yasuhara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shingo
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Muraoka
authors.forename: Yuan
authors.initials: Y
authors.lastname: wen Ji
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kameda
authors.forename: Akira
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Akimasa
authors.initials: A
authors.lastname: Yano
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nishio
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsui
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005260:Female; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D015259:Dopamine Agents; D004343:Drug Implants; D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine