Sugiyama et al.45 demonstrated direct agonism of Nrf2 which resulted in reduced secondarybrain injury in vivo and the pathogenic mechanisms invitro. Their study was subsequent to the positive outcomes inexperimental ICH demonstrated by Nrf2 agonists dimethyl fumarate,24 a multiple sclerosis therapy, and nicotinamide mononucleotide,44 an endogenous derivative of niacin. This evidence concerns the gene NFE2L2 and multiple sclerosis.