The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model
| Autor: | Akira Takeuchi, Tetsuro Shingo, Shinsaku Nishio, Akimasa Yano, Hirofumi Hamada, Yuan Wen Ji, Takao Yasuhara, Isao Date, Kenichiro Muraoka, Masahiro Kameda, Yasuyuki Miyoshi, Toshihiro Matsui |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Vascular Endothelial Growth Factor A
Pathology medicine.medical_specialty Tyrosine 3-Monooxygenase Angiogenesis Cell Survival Dopamine Dopamine Agents Striatum Pharmacology In Vitro Techniques Neuroprotection Cerebral edema Rats Sprague-Dawley chemistry.chemical_compound Mice In vivo Mesencephalon Medicine Animals Oxidopamine Molecular Biology Drug Implants Neurons Dose-Response Relationship Drug business.industry General Neuroscience Dopaminergic Capsule Parkinson Disease medicine.disease Rats Vascular endothelial growth factor Mice Inbred C57BL Neostriatum Amphetamine Disease Models Animal Neuroprotective Agents chemistry Nerve Degeneration Female Neurology (clinical) business Developmental Biology |
| Zdroj: | Brain research. 1038(1) |
| ISSN: | 0006-8993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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