Fig. 1

Schematic illustration of pathogenic mechanisms of HIE following HI brain injury. Primary energy failure occurs immediately after the hypoxic–ischemic insult. After reperfusion, there is a secondary energy failure, which can extend in duration from 6 to 48 h. Brain injury (tertiary phase) continues to occur months to years after the injury resulting in decreased plasticity and reduced number of neurons. Latent period following resuscitation is ideal for interventions to decrease the impact of secondary energy failure. However, strategies are developed to attenuate tertiary brain damage which will expand the therapeutic window, substantially increasing the beneficial effects of neuroprotection in these infants and hence its impact on long-term outcome. The up arrows represent an increase while the down arrows show a decrease in the corresponding metabolite/process