Initial etiological research of intracranial dural arteriovenous fistulas

Abstract

Objective To investigate the pathogenesis of intracranial dural arteriovenous fistula, with a focus on the role of angiogenic factors and chronic brain hypoperfusion in it. Methods 120 Sprague-Dawley rats were randomly divided into 4 groups: 1) Group A (n=25) , sham operation; 2) Group B (n = 25), thrombosis of the sagittal sinus; 3) Group C (n = 35), anastomosis of the right common carotid artery(CCA) to the external jugular vein(EJV) and occlusion of the proximate-cardiac end of the transverse sinus on the left; 4) Group D(n =35) , procedures done as Group C and thrombosis of the sagittal sinus was added. Mean arterial pressure, sinus pressure, blood flow of the brain were monitored during the operation and again tested 1, 2, 4, 12 weeks after operation in subgroups of animals, respectively. Histological examination was used to test the distribution and concentration of VEGF and MMP-9 in dura mater, arachnoid membrane, cortex and basal ganglia. Perfusion MRI of the brain was done to compare blood flow in different site of the brain. Results In group C and D, the mean blood pressure decreased soon after operation, and the sinus pressure elevated to (28.55±4. 92) mm Hg and kept stable at (22. 34 ±3.24) mm Hg 4 weeks later. The blood flow of the brain went down significantly after operation in group C and D, with markedly reduction in the right occipital lobe versus any of the other sites. Two weeks later the blood flow had returned to the normal level in the left side but remained abnormal in the right occipital lobe. Perfusion MRI found higher blood volume and longer mean time to enhance in the right occipital lobe, than in its contralateral side. Immunohistological stain of VEGF was positive in basal ganglia, right occipital lobe and arachnoid membrane one week after operation, but weakened in basal ganglia two weeks later. VEGF expression was weak in dura mater one week after operation, but became strongly positive from the 4th to 12th week after operation. The angiogenesis was prominent in the dura mater 12 weeks after operation in group C and D but negative or obscure in group A and B. Conclusions High sinus pressure was critical for angiogenesis of dura mater. Chronic brain hypoperfusion, which will elevate the expression of VEGF and MMP-9, is an important step from the progression of venous sinus pertension to DAVF formation. Key words: Dura arteriovenous fistula; Model; Rats