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

Abstract

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.

Acute traumatic dural arteriovenous fistula of the superior sagittal sinus: illustrative case

“…dAVFs may occur in the absence of venous sinus pathology and have been described to occur in relation to infection, 7 tumors, 7 , 16 , 22 post-neurosurgery, 2 , 5 , 7 , 8 , 16 , 19 , 23 hormonal imbalance, 2 , 7 , 16 , 23 hypercoagulable states, 2 , 7 , 16 , 24 , 25 and arterial dysplasia. 7 …”

“…The shunt undergoes vascular recruitment secondary to angiogenic stimulation and subsequent fistula maturation with intimal thickening and venous dilation. 9,21 dAVFs may occur in the absence of venous sinus pathology and have been described to occur in relation to infection, 7 tumors, 7,16,22 post-neurosurgery, 2,5,7,8,16,19,23 hormonal imbalance, 2,7,16,23 hypercoagulable states, 2,7,16,24,25 and arterial dysplasia. 7 Thrombophlebitis, tumor-related cytokinesis, and disruption of normal hemodynamic flow, contributing to chronic hypoperfusion and dural hypoxia, directly stimulate angiogenic factors.…”

“…7 Thrombophlebitis, tumor-related cytokinesis, and disruption of normal hemodynamic flow, contributing to chronic hypoperfusion and dural hypoxia, directly stimulate angiogenic factors. 8,13 The most commonly implicated are vascular endothelial growth factor 1,8,17,26,27 and basic fibroblast growth factor, 17,26 which are found in abundance on histological specimens of dAVFs. 17 Platelet-derived growth factor has also been found to stimulate dAVF neovascularization.…”

“…A dural arteriovenous fistula (dAVF) is an aberrant communication between meningeal arteries and venous sinuses or cortical veins. [1][2][3][4][5][6][7][8][9] They classically occur adjacent to venous sinuses, with the transverse sigmoid sinus, cavernous sinus, and superior sagittal sinus (SSS) being the most common locations. They comprise 10% to 15% of cerebral arteriovenous malformations 2,[10][11][12] and are distinguished by their meningeal supply and the absence of a vascular nidus.…”

Pentoxifylline decreases the activity of the nucleotide-binding oligomerization domain-like receptor protein 3 pathway: potential role for preventing arteriovenous fistula stenosis

“…An AVF rat model was established according to the method described previously. 15 Briefly, rats were anaesthetised by an intraperitoneal injection of 10% chloral hydrate (0.2-0.3 mL/100 g). An incision of the front middle cervix was made, and the common carotid artery and internal jugular vein were separated and exposed.…”