Immunohistochemical study in dural arteriovenous fistulas and possible role of local hypoxia for the de novo formation of dural arteriovenous fistulas

Objective : Although previous clinical and experimental studies investigated the pathogenesis of dural arteriovenous fistulas (DAVFs), the biological process leading to intracranial DAVFs so far remains unknown. In this study, we investigated the expression of vascular growth factors in order to elucidate the possible role of these factors in the development of DAVFs. Methods : We examined the histological features, proliferative and angiogenic capacities of the tissue specimens obtained from eight patients who underwent surgery at our institution. Immunohistochemical staining for vascular endothelial growth factor (VEGF), its receptors Flk-1 and Flt-1, transforming growth factor alpha (TGFα), basic fibroblast growth factor (bFGF), hypoxia inducible factor 1α (Hif-1α), MIB-1 and proliferating cell nuclear antigen (PCNA) was performed using standard immunohistochemical techniques. Results : A positive immunostaining was found for all antibodies studied except MIB-1, whereas nuclear endothelial expression of PCNA was observed in only 3/8 cases. Hif-1α and VEGF stained positive in all of the available specimens (7/7). Flk-1 showed a positive immunoreaction in only 2/8 cases and Flt-1 in 5/7 cases. TGFα and bFGF were expressed in the majority (6/8) of cases. Conclusion : These results indicate the possible role of local tissue hypoxia as the initial step causing neoangiogenesis and a low degree of endothelial proliferation in DAVFs. Such hypoxia might be caused by venous hypertension or venous thrombosis as it was previously suggested by other authors.