Figure 5.

Working model of the protective effects of MH/EDA on MCAO-induced cognitive deficits (red arrow, effect of MCAO; green arrow, effect of MH/EDA). MCAO caused cognitive deficits through promoting mitochondrial dysfunction and increasing the oxidative stress level. The Nrf2/HO-1 pathway was activated as protection against oxidative stress. The promoting effect on mitochondrial dysfunction and oxidative stress induced an increase in cytochrome c and caspase-3 levels, thereby inducing cell apoptosis and neuronal death. Combined therapy with MH and EDA play a protective role through promoting the activation of the Nrf2/HO-1 pathway, thereby reducing the oxidative stress and mitochondrial dysfunction. MCAO, middle cerebral artery occlusion; MH, mild hypothermia; EDA, edaravone; Nrf2, nuclear factor erythroid 2-related factor 2; HO-1, heme oxygenase-1.