Angiogenesis is present in experimental autoimmune encephalomyelitis and pro-angiogenic factors are increased in multiple sclerosis lesion
Timothy J Seabrook, Amanda Littlewood-Evans, Volker Brinkmann, Bernadette Pollinger, Christian Schnell, Peter C Hiestand
Journal of Neuroinflammation 2010, 7:95 doi:10.1186/1742-2094-7-95
Angiogenesis 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.
In 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.
Vascular 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 3 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.
These findings reveal that angiogenesis is intimately involved in the progression of EAE and may have a role in MS