Abstract
BackgroundAngiogenesis is a common finding in chronic inflammatory diseases; however, its role in multiple sclerosis (MS) is unclear. Central nervous system lesions from both MS and experimental autoimmune encephalomyelitis (EAE), the animal model of MS, contain T cells, macrophages and activated glia, which can produce pro-angiogenic factors. Previous EAE studies have demonstrated an increase in blood vessels, but differences between the different phases of disease have not been reported. Therefore we examined angiogenic promoting factors in MS and EAE lesions to determine if there were changes in blood vessel density at different stages of EAE.MethodsIn this series of experiments we used a combination of vascular casting, VEGF ELISA and immunohistochemistry to examine angiogenesis in experimental autoimmune encephalomyelitis (EAE). Using immunohistochemistry we also examined chronic active MS lesions for angiogenic factors.ResultsVascular casting and histological examination of the spinal cord and brain of rats with EAE demonstrated that the density of patent blood vessels increased in the lumbar spinal cord during the relapse phase of the disease (p < 0.05). We found an increased expression of VEGF by inflammatory cells and a decrease in the recently described angiogenesis inhibitor meteorin. Examination of chronic active human MS tissues demonstrated glial expression of VEGF and glial and blood vessel expression of the pro-angiogenic receptor VEGFR2. There was a decreased expression of VEGFR1 in the lesions compared to normal white matter.ConclusionsThese findings reveal that angiogenesis is intimately involved in the progression of EAE and may have a role in MS.
Highlights
Angiogenesis is a common finding in chronic inflammatory diseases; its role in multiple sclerosis (MS) is unclear
Blood vessel density increases during EAE To investigate whether angiogenesis is present during EAE, vascular casting was performed during the acute and relapse phase of disease and compared to those obtained from naive rats
The grey matter is located in the center of the cast and in healthy rats it is known that this area contains a greater number of blood vessels [27]
Summary
Angiogenesis is a common finding in chronic inflammatory diseases; its role in multiple sclerosis (MS) is unclear. Central nervous system lesions from both MS and experimental autoimmune encephalomyelitis (EAE), the animal model of MS, contain T cells, macrophages and activated glia, which can produce pro-angiogenic factors. The exact cause of MS is unclear but appears to be a complex interaction of genetic, environmental and perhaps infectious causes [3,4]. It is characterized by multifocal inflammatory lesions in the white matter. Besides the well characterized inflammatory infiltrate, disturbances in the blood brain barrier (BBB) occur in both MS and the animal model, experimental autoimmune encephalomyelitis (EAE) [6,7,8]. The role of the blood vessels in initiation, propagation and resolution of MS plaque formation is still unclear
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