Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that vascular endothelial growth factor (VEGF) expression is up-regulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the disease. However, it remains unknown whether anti-VEGF modalities could serve as a potential treatment for such central nervous system (CNS) autoimmune diseases. We constructed a recombinant adenoviral vector carrying FLAG-tagged sFlt-1(1-3) (the first three extracellular domains of Flt-1, the hVEGF receptor-1). Intramuscular transfection of the recombinant adenoviral vector suppressed VEGF-induced inflammatory cell infiltration in matrigel plugs. When given intracerebrally to EAE rats, recombinant sFlt-1(1-3) adenoviral vector significantly reduced disease severity compared to untreated rats. sFlt-1(1-3) gene transfer blocked VEGF and greatly reduced the number of cells that express VEGF and ED1-positive cells in CNS in EAE rats. This study demonstrates that sFlt-1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting monocyte recruitment in the CNS of dark Agouti rats.
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PMID:Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental autoimmune encephalomyelitis in dark Agouti (DA) rats. 1872 16

We investigated the spatiotemporal expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. VEGFR-3 mRNA and protein were constitutively expressed in gray matter neurons and in a few white matter astrocytes. Induction of VEGFR-3 occurred predominantly in perivascular infiltrated macrophages in the spinal cord white matter during the inductive phase of EAE. VEGFR-3 expression was also induced in activated microglial cells in the gray and white matter, mainly in the peak phase. In addition, reactive astrocytes in the white matter, but not in the gray matter, expressed VEGFR-3 as disease severity increased. These data suggest that VEGFR-3 is involved in the recruitment of monocytic macrophages and in glial reactions during EAE.
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PMID:Upregulation of vascular endothelial growth factor receptor-3 in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis. 2298 93

Angiogenesis, a prominent feature of pathology, is known to be guided by factors secreted by living cells around a lesion. Although many cells are disrupted in a response to injury, the relevance of degenerating cells in pathological angiogenesis is unclear. Here, we show that the release of lactate dehydrogenase A (LDHA) from degenerating neurons drives central nervous system (CNS) angiogenesis. Silencing neuronal LDHA expression suppressed angiogenesis around experimental autoimmune encephalomyelitis (EAE)- and controlled cortical impact-induced lesions. Extracellular LDHA-mediated angiogenesis was dependent on surface vimentin expression and vascular endothelial growth factor receptor (VEGFR) phosphorylation in vascular endothelial cells. Silencing vimentin expression in vascular endothelial cells prevented angiogenesis around EAE lesions and improved survival in a mouse model of glioblastoma. These results elucidate novel mechanisms that may mediate pathologic angiogenesis and identify a potential molecular target for the treatment of CNS diseases involving angiogenesis.
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PMID:Extracellular Lactate Dehydrogenase A Release From Damaged Neurons Drives Central Nervous System Angiogenesis. 2924 8