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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic Agents / toxicity
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Amphetamine / pharmacology
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Animals
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Behavior, Animal
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Body Weight / drug effects
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Brain / anatomy & histology
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Brain / drug effects
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Brain / physiopathology
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Capsules
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Cell Count
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Cell Death / drug effects
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Cells, Cultured
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Central Nervous System Stimulants / pharmacology
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Cricetinae
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Disease Models, Animal
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Dopamine / metabolism*
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Dose-Response Relationship, Drug
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Enzyme-Linked Immunosorbent Assay
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Functional Laterality
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Glial Fibrillary Acidic Protein / metabolism
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Humans
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Immunohistochemistry
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In Situ Nick-End Labeling / methods
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Kidney
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Laminin / metabolism
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Laser-Doppler Flowmetry / methods
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Mesencephalon / cytology
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Mice
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Mice, Inbred C57BL
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Neurons / drug effects*
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Neuropilins / metabolism
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Oxidopamine / toxicity
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Parkinson Disease / pathology*
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Rats
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Rats, Sprague-Dawley
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Semaphorin-3A / metabolism
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Stereotyped Behavior / drug effects
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Time Factors
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Transfection / methods
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Transplants
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Tubulin / metabolism
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Tyrosine 3-Monooxygenase / metabolism
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
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Vascular Endothelial Growth Factor A / pharmacology*
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Vascular Endothelial Growth Factor Receptor-1 / metabolism
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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Adrenergic Agents
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Capsules
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Central Nervous System Stimulants
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Glial Fibrillary Acidic Protein
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Laminin
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Neuropilins
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Semaphorin-3A
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Tubulin
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Vascular Endothelial Growth Factor A
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Oxidopamine
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Amphetamine
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Tyrosine 3-Monooxygenase
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2
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Dopamine