The Role And Mechanism Of Oxidative Stress In Cerebral Arteriovenous Malformation Development And Rupture

Background Cerebral arteriovenous malformation (cAVM) is closelyassociated with inflammatory reactions, which are features of oxidative stress. In thisstudy, we investigated the roles of oxidative stress in the cAVM.Methods cAVM patients were divided into unruptured and ruptured groupsaccording to whether they had a history of cerebral hemorrhage. Patients withtraumatic brain injury were used as controls. Plasma levels of superoxide dismutase(SOD), glutathione peroxidase (GSH-px）, and malondialdehyde (MDA) weremeasured with chemical colorimetry. Western-blot was used to assess the content ofextracellular signal-regulated kinase (ERK)1/2, p-ERK1/2, and hypoxia induciblefactor-1(HIF-1)-1α in blood vessels. The plasma levels of vascular endothelialgrowth factor (VEGF) and basic fibroblast growth factor (bFGF) were determinedwith ELISA.Results The activities of SOD and GSH-px in both cAVM groups weresignificantly lower than for controls. In contrast, the levels of MDA in both cAVMgroups were significantly higher. Western-blot showed that the relative content ofp-ERK1/2and HIF-1α were significantly elevated in the cAVM groups compared tocontrols. The levels of VEGF in the cAVM groups were significantly higher than forcontrols.Conclusions Oxidative stress may directly cause injury and rupture of thevessel walls in cAVM, as well as cause indirect injury by activating the ERK-HIF-VEGF pathway so that neovascularization occurs in deformed vessels.