Open Accesshysiological and Biochemical Changes in NRF2 Pathway in Aged Animals Subjected to Brain Injury
Author(s) -
Massimiliano Cordaro,
Ramona D’Amico,
Rossana Morabito,
Roberta Fusco,
Rosalba Siracusa,
Alessio Filippo Peritore,
Daniela Impellizzeri,
Tiziana Genovese,
Rosalia Crupi,
Enrico Gugliandolo,
Angela Marino,
Rosanna Di Paola,
Salvatore Cuzzocrea
Publication year - 2021
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.33594/000000353
Subject(s) - oxidative stress , medicine , inflammation , stroke (engine) , traumatic brain injury , ischemia , keap1 , endocrinology , pathology , physiology , biology , biochemistry , transcription factor , gene , mechanical engineering , psychiatry , engineering
Background/Aims: 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. Methods: Young and old mice were subjected to focal cerebral ischemia induced by transient middle cerebral artery occlusion or to traumatic brain injury performed by a controlled cortical impactor. At the end of both experiments, mice were sacrificed 24h after injuries and brains were collected to perform biochemical analysis. Results: 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-Keap1 signalling pathway and lower expression of antioxidant enzymes, such as HO-1, SOD-1 and GSH-Px. Additionally, brain tissues collected from elderly mice showed an increased IκB-α degradation into the cytoplasm and consequently NF-κB 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. Conclusion: 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. Not only that, NRF-2 pathway could represent a possible therapeutic target in the management of brain injuries.