Physiological and biochemical changes in NRF2 pathway in aged animals subjected to brain injury

Oxidative stress plays a key role in aging, which in turn represents a substantial risk factor for brain injuries. The aim of the present study was to investigate the differences in physiological and biochemical changes in the brain during injury‐related inflammation and oxidative stress, comparing young and old mice. In both ischemic stroke and traumatic brain injury, aging has not only led to damage‐induced worsening of motor function and behavioural changes but also increased of infarct area compared to young animals. Moreover, aged mice show increased evidence of oxidative stress and reduced antioxidant capacity when compared to younger animals, as demonstrated by Nrf2‐Keap1signalling pathway and lower expression of antioxidant enzymes, such as HO‐1, SOD and GSH‐Px. Additionally, brain tissues collected from elderly mice showed an increased IkB‐α degradation into the cytoplasm and consequently NF‐kB translocation into the nucleus, compared to young mice subjected to same injuries. The elderly mice showed significantly higher levels of iNOS and CoX‐2 expression than the young mice, as well as higher levels of inflammatory cytokines such as TNFα, IL‐1β, and IL‐6 after MCAO and TBI. Preserving and keeping the NRF‐2 pathway active counteracts the onset of oxidative stress and consequent inflammation after ischemic and traumatic brain insult, particularly in the elderly. Aging represents an important risk factor in functional recovery after ischemic and traumatic brain damage. Not only that, NRF‐2 pathway could represent a possible therapeutic target in the management of brain injuries.