Furthermore, neither levels of HO-1 mRNA nor its protein expression was altered upon DMF or MMF treatment in Nrf2–/– mice with MCAO ischemia–reperfusion injury (Supplemental Fig. 3).These findings suggest that the Nrf2 pathway is essential for DMF and MMF to exert their protective role in brain ischemia–reperfusion injury. Here, HMOX1 is linked to brain ischemia.