Neurorescue effects of VEGF on a rat model of Parkinson's disease

Autor: Hitoshi Hayase, Hirofumi Hamada, Masahiro Kameda, Tetsuro Shingo, Yuan Wen Ji, Takashi Agari, Cesario V. Borlongan, Isao Date, Takao Yasuhara, Kenichiro Muraoka
Rok vydání: 2005
Předmět:
Vascular Endothelial Growth Factor A
Time Factors
Cell Transplantation
Dopamine
Cell Count
Striatum
Pharmacology
Rats
Sprague-Dawley
Mice
chemistry.chemical_compound
Mesencephalon
Cricetinae
Drug Interactions
Cells
Cultured
Neurons
Behavior
Animal
General Neuroscience
Brain
Parkinson Disease
Immunohistochemistry
Vascular endothelial growth factor
Neuroprotective Agents
medicine.anatomical_structure
Neuroglia
Female
Rotation
Tyrosine 3-Monooxygenase
Enzyme-Linked Immunosorbent Assay
Substantia nigra
Biology
Transfection
Neuroprotection
Adrenergic Agents
In vivo
Glial Fibrillary Acidic Protein
medicine
Animals
Humans
Oxidopamine
Molecular Biology
Analysis of Variance
Dose-Response Relationship
Drug
Pars compacta
Body Weight
Embryo
Mammalian
Rats
Transplantation
Amphetamine
Disease Models
Animal
nervous system
chemistry
Laminin
Neurology (clinical)
Neuroscience
Developmental Biology
Zdroj: Brain Research. 1053:10-18
ISSN: 0006-8993
DOI: 10.1016/j.brainres.2005.05.027
Popis: Vascular endothelial growth factor (VEGF) has been shown to display neuroprotective effects on dopaminergic (DA) neurons. Here, we investigated the neurorescue effects of VEGF on 6-hydroxydopamine (6-OHDA)-treated DA neurons in vitro and in vivo. Initially, we examined in vitro whether 1, 10, or 100 ng/ml of VEGF administration at 2 or 4 h after 6-OHDA treatment rescued DA neurons derived from E14 murine ventral mesencephalon. The earlier treatment of VEGF suppressed 6-OHDA-induced loss of DA neurons more than the delayed treatment. Next, we examined whether the continuous infusion of VEGF had neurorescue effects in a rat model of Parkinson's disease. We established a human VEGF secreting cell line (BHK-VEGF) and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally transplanted into the striatum of adult rats at 1 or 2 weeks after 6-OHDA lesions, and animals subsequently underwent behavioral and immunohistochemical evaluations. Compared to lesioned rats that received BHK-Control capsules, lesioned rats transplanted with BHK-VEGF capsules showed a significant reduction in the number of amphetamine-induced rotations, a significant preservation of TH-positive neurons in the substantia nigra pars compacta, and a remarkable glial proliferation in the striatum, with the earlier transplantation exerting much more benefits than the delayed transplantation. Parallel studies revealed that the observed in vitro and in vivo neurorescue effects were likely mediated by VEGF's angiogenic and glial proliferative effects, as well as its direct effects on the neurons. Our results suggest that VEGF is a highly potent neurorescue molecule for Parkinson's disease therapy.
Databáze: OpenAIRE
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