Neuroprotection by Manganese Superoxide Dismutase (MnSOD) Mimics: Antioxidant Effect and Oxidative Stress Regulation in Acute Experimental Stroke

Abstract

MnSOD is an effective therapeutic target in ischemic stroke prevention because of its antioxidant effects and oxidative stress regulation.

Role of mitochondrial function in the protective effects of ischaemic postconditioning on ischaemia/reperfusion cerebral damage

“…43,44 Mitochondrial swelling was shown to begin at the start of cerebral ischaemia and was exaggerated by subsequent reperfusion, reaching its peak after 24 h of reperfusion. 48 Transmission electron microscopy studies found that damaged mitochondria exhibited severe collapse in both the inner and outer membranes after 24 h reperfusion following 2 h of ischaemia, and exhibited irregular shape, electronlucent matrix, fragmented cristae, and extreme dilation of the intracristal space.…”

“…Decreased MnSOD activity has been found to exacerbate glutamate toxicity in cultured mouse cortical neurons, 43 and MnSOD mimics could prevent neural apoptosis and reduce ischaemic brain injury by maintaining mitochondrial function. 44 Mitochondrial MnSOD therefore plays a crucial role in maintaining the function of mitochondria. It is possible that the protective effect of ischaemic postconditioning may be mediated via modulation of MnSOD, reducing the increase in mitochondrial ROS caused by cerebral ischaemia/reperfusion.…”

Angiopep-2-Mediated Delivery of Human Manganese Superoxide Dismutase in Brain Endothelial Cells and its Protective Effect Against Oxidative Stress

“…The enzyme has been considerable interested because of its role in protection against human diseases (Faraci and Didion 2004;Fukai and UshioFukai 2011). Manganese superoxide dismutase (MnSOD or SOD2) is one of the most crucial antioxidants in the central nervous system (CNS) and is thought to be one of the major mechanisms to counteract injuries of reactive oxygen species (ROS) after cerebral ischemia (Huang et al 2012;Jung et al 2009;Kim et al 2002;Lebovitz et al 1996). The comparative pharmacokinetic studies in rats demonstrated that MnSOD had longer serum half-life than Cu/ZnSOD indicating the superior advantage of MnSOD for the treatment of chronic diseases (Baret et al 1984;Gorecki et al 1991).…”

Comparação dos efeitos da ressuscitação com Ringer lactato, solução salina hipertônica e terlipressina sobre a perfusão e oxigenação cerebral em modelo experimental de choque hemorrágico

“…Entre os mecanismos de defesas antioxidantes, a superóxido dismutase desempenha um importante papel na prevenção da apoptose neuronal, protegendo os neurônios das ROS. Em particular, a superóxido dismutase dependente de manganês (MnSOD) mitocondrial é capaz de reduzir a apoptose neuronal por suprimir a lipoperoxidação e produção de peroxinitrito e evitar a disfunção mitocondrial (Huang et al, 2012).…”

“…Apesar do aumento compensatório na expressão de MnSOD, este mecanismo de defesa antioxidante não foi suficiente para evitar a ativação da via intrínseca de apoptose, que pode ter sido também ativada pela hipóxia, resultando na redução da relação Bcl-x/Bax (Guven et al, 2002;Huang et al, 2012;Tsai et al, 2007;Chen et al, 2012). As proteínas Bcl-x e Bax desempenham um papel importante na determinação da sensibilidade relativa de subpopulações neuronais à isquemia e ROS para início da apoptose (Krajewski et al, 1995;Mishra et al, 2006).…”