Study on the mechanisms responsible for the development and growth of dural arteriovenous fistula

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Although various mechanisms of the development of dural arteriovenous fistula(DAVF) have been proposed, the pathogenesis of these lesions are still unclear. Recent experimental evidence suggested a role of angiogenic growth factors in the genesis of vascular malformations of the central nervous system. To further investigate the pathogenesis of DAVF, we examined the expression of the angiogenic growth factor, vascular endothelial growth factor(VEGF), in rat DAVF model.<Experiment-1> Male Wistar rats were used. DAVF model (Spetzler) was made, and venous hypertension was induced which were divided into two experimental groups ; immunohistological study group and angiography group. Immunohistological analysis was performed by VEGF antibody 1 week after, and angiography was done 90 days after the surgery. As a result, VEGF expression in the endothelium and the connective tissues of the dura matter in the five rats (33%) and in the neurons in the eleven rats (73%) of the cerebral cortex and the basal ganglia were identified. DAVF formed in 6 among 15 rats (40%). <Experiment-2> Western blot was performed with different periods from 1, 2 and 3 weeks after inducing venous hypertension in the same model. The expression of VEGF was peaked at one week after venous hypertension, and decreased by the order of two and three weeks (1>2>3 week). The expression of immunoreactive VEGF was restricted in the connective tissue and the endothelial layer of the dura matter, cerebral cortical tissue and basal ganglia neurons.In conclusions, these results strongly suggest a possible contribution of the VEGF system to the growth of DAVF. Venous ischemia by venous hypertension might be responsible for inducing up-regulation of angiogenic factor expression.