Dimethyl Fumarate And Monomethyl Fumarate Promote Post-Ischemic Recovery In Mice
Oxidative stress plays an important role in cerebral ischemiaâ€“reperfusion injury. Dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) are antioxidant agents that can activate the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and induce the expression of antioxidant proteins. Here, we evaluated the impact of DMF and MMF on ischemia-induced brain injury and whether the Nrf2 pathway mediates the effects provided by DMF and MMF in cerebral ischemiaâ€“reperfusion injury. Using a mouse model of transient focal brain ischemia, we show that DMF and MMF significantly reduce neurological deficits, infarct volume, brain edema, and cell death. Further, DMF and MMF suppress glial activation following brain ischemia. Importantly, the protection of DMF and MMF was mostly evident during the subacute stage and was abolished in Nrf2âˆ’/âˆ’ mice, indicating that the Nrf2 pathway is required for the beneficial effects of DMF and MMF. Together, our data indicate that DMF and MMF have therapeutic potential in cerebral ischemiaâ€“reperfusion injury and their protective role is likely mediated by the Nrf2 pathway.
Translational Stroke Research
Digital Object Identifier (DOI)
Yao, Yang; Miao, Weimin; Liu, Zhijia; Han, Wei; Shi, Kaibin; Shen, Yi; Li, Handong; Liu, Qiang; Fu, Ying; Huang, De Ren; and Shi, Fu Dong, "Dimethyl Fumarate And Monomethyl Fumarate Promote Post-Ischemic Recovery In Mice" (2016). Neurobiology. 137.