Cognitive and neuropsychiatric impairments vary as a function of injury severity at 12 months post-experimental diffuse traumatic brain injury: Implications for dementia development

Abstract

Traumatic brain injury (TBI) is a common risk factor for later neurodegeneration, which can manifest as dementia. Despite this, little is known about the time-course of development of functional deficits, particularly cognitive and neuropsychiatric impairments, and whether these differ depending on the nature of the initiating insult. Therefore, this study investigated long term functional impairment at 12 months post-injury following diffuse TBI of different severities. Male Sprague-Dawley rats (420-480 g; 10-12 weeks) were either given a sham surgery (n = 14) or subjected to Marmarou's impact acceleration model of diffuse TBI for a single mild TBI (n = 12), repetitive mild TBI (3 mild diffuse injuries at 5 day intervals) (n = 14) or moderate to severe TBI (n = 14). At 12 months after injury, they were tested on a functional battery encompassing motor, neuropsychiatric (anxiety and depressive-like) and cognitive function. Our results showed that moderate to severe TBI animals exhibited significant impairments in cognitive flexibility (p = 0.009) on the Barnes maze when compared to age-matched sham animals. Neither repetitive mild TBI nor single mild TBI animals showed significant functional impairments when compared to shams. Thus, this study provides the first insight into chronic functional impairments associated with different severities of diffuse TBI, with moderate to severe TBI being a higher risk factor for impaired cognitive function at 12 months post-injury. Taken together, this may have implications for risk of dementia development following different severities of injury.

Keywords: Anxiety; Chronic outcomes; Cognition; Diffuse injury; Injury severity.