Inflammation and oxidative damage as risk factors of neurodegeneration after Traumatic Brain Injury in young and aged mice

Traumatic Brain Injury (TBI) causes transitory or permanent structural and functional impairments and may increase the risk of neurodegeneration. As age correlates with development of neurodegenerative disease after TBI, the aim of the present study was to verify the possible onset of neurodegeneration after TBI and the related pathways, namely associated to oxidative stress and neuroin!ammation in both young (3 months) and aged mice (12 months). TBI was induced in mice by controlled cortical impact and behavioral tests (open "eld, elevated plus maze, novel object recognition, Morris water maze) performed after 30 days and 3 months of trauma. Thereafter, the animals were sacri"ced and the brains processed for Western blot and immunohistochemical analyses. In particular, IL‐6, IL‐8 and TNF‐a levels accounting for in!ammation and malonildialedhyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) levels accounting for oxidative damage have been monitored. With regard to behavioural anaylis at both time intervals after TBI, aged animals exhibited a more pronounced anxiety‐like behavior along with impaired memory than what estimated in young animals. Moreover, a strong increase in neuroin!ammation, shown by increased levels of cytokines, and oxidative damage, attested by increased MDA and GSH along with decreased SOD quantity suggested that neuroin!ammation and oxidative stress damage were more signi"cantly exhibited by aged than young mice. The present study suggests that aging may exacerbate the damage deriving from TBI and increases the risk of neurodegeneration due to oxidative stress and in!ammation response, with speci"c regard to anxietylike behavior. Further studies may be useful to monitor risk factors of neurodegenerative diseases over a longer time lapse after TBI, namely in aged animal, in order to add more knowledge about development of neurodegeneration. Considering the complex multifactorial nature of neurodegenerative diseases, a preventive strategy able to simultaneously target multiple risk factors and disease mechanisms at an early stage is most likely to be e#ective to slow/halt the progression of neurodegenerative diseases