Cognitive training and functional recovery in an aged model of traumatic brain injury.

摘要

Increased age at the time of insult is one of the strongest indicators of poor outcome following traumatic brain injury (TBI), but few preclinical studies attempt to evaluate potential treatments or therapies in older subjects. It appears that cognitive functioning is especially sensitive to age-related decline, and such deficits are exacerbated by TBI. Although preclinical evaluations of environmental enrichment (EE) has produced a wealth of information that indicates more complex environments are correlated with improved functional recovery, few studies have attempted to assess this paradigm in older individuals. The purpose of this project was to examine the usefulness of cognitive training to facilitate functional recovery in aged animals following traumatic brain injury. Aged (21 month old) Fischer 344 male rats were used to evaluate cognitive status prior to injury as well as the effectiveness of cognitive training following injury for each of these groups. Aged animals were characterized for cognitive ability on the Morris Water Maze (MWM) task prior to cortical contusion injury. Based on this evaluation, animals were then placed into an injury condition (cortical injury over the hippocampus or sham-injury) and cognitive training manipulation (cognitive training in the Dig task or no cognitive training). Following injury, animals in the cognitive training condition were shaped to dig in cups filled with sand for buried food reinforcer. Later, animals in this condition were trained on various olfactory discrimination tasks with scented sand for the food reinforcer. After four weeks of training on the task, the animals were again evaluated in the MWM using both reference and working memory paradigms on the task. There was a significant benefit of the cognitive training in the injured animals, but only on the reference memory task. It also appears that cognitive ability before injury does influence the efficacy of the behavioral intervention. Indeed, among the injured animals that were characterized as cognitively impaired, those that received the training demonstrated enhanced cognitive recovery on the reference memory task. Despite these behavioral differences, the groups did not differ in lesion size or on measures of blood-brain barrier compromise or astrocytic activation. These findings indicate that cognitive training can confer positive results, even in the most aged or cognitively impaired individuals. These effects were achieved even though the olfactory discrimination cognitive training task and the spatial MWM task are in differing cognitive domains. These effects may exist because success on the species-relevant, hippocampal-mediated cognitive training task requires attention to environmental cues and a dynamic environment. The findings of this study may contribute to the design of increasingly efficacious behavioral interventions following TBI to better facilitate functional recovery of cognitive abilities, especially in the more vulnerable aged individuals.