Age, but not severity of injury, mediates decline in executive function: Validation of the rodent touchscreen paradigm for preclinical models of traumatic brain injury

摘要

Increasingly, it is being recognised that traumatic brain injury (TBI) is not just an acute event but instead results in ongoing neuronal injury that may lead to chronic impairments in multiple cognitive domains. Of these, deficits in executive function are one of the more common changes reported following TBI, and are a major predictor of well-being, social function and quality of life in individuals with a history of TBI. In order to fully understand the relationship between TBI and executive dysfunction, including brain mechanisms that may account for this, experimental models are clearly needed. However, to date, there have been a lack of preclinical studies systematically comparing the effect of injury severity on executive function, particularly at long-term timepoints post-injury. Furthermore, many previous studies have not used behavioural measures that are sensitive to the full range of executive function impairments that may manifest after injury, particularly in models of diffuse axonal injury (Lv et al.). The current study aimed to investigate the temporal profile, up to 12 months post-injury, of the evolution of executive dysfunction following different severities of injury in an experimental model of DAI. In order to do so, we utilised a rodent touchscreen paradigm to administer the 5 Choice Continuous Performance Task (5C-CPT), an extension of the 5-choice serial reaction time task (5CSRT). Interestingly, there were no differences in learning, motivation, attention, response time or impulsivity at 1 month, 6 months or 12 months post-injury in any of the TBI groups compared to sham, regardless of the initial severity of the injury. Instead, most of the effects on executive function seen at the 12 month timepoint appeared to be a result of ageing, not injury. As even the 12-month timepoint represents middle age in the rat, future studies will be needed to further probe these effects, in order to determine whether DAI may influence the presentation of executive dysfunction in older age.