Nitrones, Old Fellows for New Therapies in Ischemic Stroke

Abstract

Ischemic stroke is suffered by millions of people worldwide, being the second cause of death in 2012. To date, only recombinant tissue plasminogen activator and thrombectomy, as first-line recanalization approaches, are the only treatments approved for ischemic stroke therapy. Nevertheless, the low number of patients who can benefit from this treatment, as well as the limited beneficial outcome, even if proper recanalization rates are achieved, make evident the need for complementary therapeutic approaches. Among them, the neuroprotection strategy appeared as a promising approach which led to the development of drugs targeting distinct steps of the biochemical pathways that take place during and after the ischemic insult. However, no effective translation from preclinical studies to clinical use has been achieved until now, rising thus doubts about the suitability of the neuroprotection therapeutic strategy. Regarding the intrinsic complexity of ischemic stroke, pleiotropy has been proposed as a key issue, and nitrones, known to act as radical traps, have arisen as interesting drug candidates. From its widely known antioxidant behavior, new mechanisms of action have been proposed based on reported evidence. In this chapter, nitrones pleiotropy is reviewed. Specific results of nitrones developed by our group are reported and discussed.