Abstract
Vascular endothelial growth factor A (VEGF-A) stimulates angiogenesis, but is also pro-inflammatory and plays an important role in the development of neurological disease, where it can have both attenuating and exacerbating effects. VEGF-B, a related molecule, is highly expressed in the central nervous system and seems to be important in neurological injury. A few studies have indicated that VEGF-A may play a role in the pathogenesis of multiple sclerosis (MS), but the role of VEGF-B has not been studied. We have studied the expression of VEGF-A, -B and their receptors by mRNA in situ hybridization, immunohistochemistry and real-time PCR in spinal cord from LEW rats with experimental autoimmune encephalomyelitis (EAE) and in cerebrospinal fluid (CSF) and blood samples from MS patients. Whereas VEGF-A is downregulated in glia in EAE, the infiltrating inflammatory cells are positive for VEGF-A. Expression of VEGF-B and the VEGF receptors is unaltered. In addition, the levels of VEGF-A mRNA in mononuclear cells [corrected] in CSF are lower in MS patients compared with controls. These results demonstrate a complex regulation of VEGF-A during neuroinflammation and suggest that VEGF-B is not involved in the pathogenesis of MS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Alternative Splicing
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Animals
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Cerebrospinal Fluid / cytology
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Down-Regulation*
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / metabolism*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Humans
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Leukocytes, Mononuclear / chemistry
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Leukocytes, Mononuclear / metabolism*
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Male
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Middle Aged
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Multiple Sclerosis / genetics
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Multiple Sclerosis / metabolism*
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Multiple Sclerosis / pathology
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Neuroglia / chemistry
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Neuroglia / metabolism
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Neuroglia / pathology
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Neurons / chemistry
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Neurons / metabolism
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Neurons / pathology
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred Lew
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Spinal Cord / metabolism
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Spinal Cord / pathology
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Vascular Endothelial Growth Factor A / analysis
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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 B / analysis
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Vascular Endothelial Growth Factor B / genetics
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Vascular Endothelial Growth Factor B / metabolism
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Vascular Endothelial Growth Factor Receptor-1 / analysis
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-1 / metabolism
Substances
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RNA, Messenger
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor B
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Vascular Endothelial Growth Factor Receptor-1