Expression of NF-E2-related factor 2 in a rat dural arteriovenous fistula model.

Abstract

Intracranial dural arteriovenous fistulas (DAVFs) are complex intracranial vascular malformations that may lead to hemorrhage. Although the precise mechanisms by which DAVFs occur remain unknown, dural angiogenesis may be a vital factor in its pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) significantly influences angiogenesis; however, the association between DAVF and Nrf2 remains unclear. Therefore, the present study investigated whether DAVF alters the expression of Nrf2 in an experimental animal model of DAVF. The DAVF group underwent surgery of the left common carotid artery-external jugular vein anastomosis, cauterization of the vein draining transverse sinus and thrombosis of the sagittal sinus to induce venous hypertension (VH). At 1, 4 and 7 days post surgery, rats were sacrificed to collect brain samples. Western blot analysis, immunofluorescence staining and reverse transcription-quantitative polymerase chain reaction were used to determine whether DAVF activated the Nrf2 signaling pathway. The results demonstrated that the expression of Nrf2 mRNA and protein, and the expression of its downstream genes heme oxygenase-1 and NAD(P)H: quinine oxidoreductase-1 significantly increased 1 day after surgery. The expression of these genes decreased but remained high 4 days following surgery and only returned to baseline 7 days after surgery. Compared with the sham-surgery and control groups, DAVF-induced brain edema reached a peak 1 day following DAVF surgery and only returned to normal levels 7 days post-surgery. Taken together, these data indicate the potential contribution of Nrf2 to the formation of DAVFs and suggest that VH may induce the upregulation of Nrf2.