Therapeutic potential of targeting hydrogen peroxide metabolism in the treatment of brain ischaemia

For many years after its discovery, hydrogen peroxide (H2O2) was viewed as a toxic molecule to human tissues; however, in light of recent findings, it is being recognized as an ubiquitous endogenous molecule of life as its biological role has been better elucidated. Indeed, increasing evidence suggests that H2O2 may act as a second messenger with a pro-survival role in several physiological processes. In addition, our group has recently demonstrated neuroprotective effects of H2O2 on in vitro and in vivo ischaemic models through a catalase (CAT) enzyme-mediated mechanism. Therefore, the present review summarizes experimental data supporting a neuroprotective potential of H2O2 in ischaemic stroke that has been principally achieved by means of pharmacological and genetic strategies that modify either the activity or the expression of the superoxide dismutase (SOD), glutathione peroxidase (GPx) and CAT enzymes, which are key regulators of H2O2 metabolism. It also critically discusses a translational impact concerning the role played by H2O2 in ischaemic stroke. Based on these data, we hope that further research will be done in order to better understand the mechanisms underlying H2O2 functions and to promote successful H2O2 signalling based therapy in ischaemic stroke.