RESUMO
Environmental enrichment (EE) consists of increased living space, complex stimuli, and social interaction that collectively confer neurobehavioral benefits in preclinical models of traumatic brain injury (TBI). The typical EE approach entails implementation immediately after surgery and continual exposure, which is not clinically applicable, as TBI patients often only receive rehabilitation after critical care, and then only for a few hours per day. We are focused on developing a clinically relevant model of neurorehabilitation by refining the timing of initiation and duration of EE exposure after TBI. The goal of this experiment is to compare the typical EE approach to paradigms where EE is delayed by 3 or 7 days after TBI and then provided for only 6 h per day, which better mimics the clinic. The hypothesis is that the delayed-and-abbreviated EE paradigms will promote neurobehavioral benefits like the typical approach of immediate-and-continuous exposure. To test the hypothesis, anesthetized adult male rats underwent a controlled cortical impact of moderate severity (2.8 mm deformation at 4 m/s) or sham injury and then were randomly assigned to post-operative EE or standard (STD) housing. Motor ability, spatial learning, and memory retention were assessed. The hypothesis was confirmed as all EE-treated groups performed better than the STD group in all behavioral assessments (p < 0.05) and did not differ from one another (p > 0.05). The ability of EE to provide significant behavioral benefits even when delayed and delivered in moderation affords further support for EE as a preclinical model of neurorehabilitation and offers greater insight into the length of the therapeutic window.
RESUMO
The typical environmental enrichment (EE) paradigm, which consists of continuous exposure after experimental traumatic brain injury (TBI), promotes behavioral and histological benefits. However, rehabilitation is often abbreviated in the clinic and administered in multiple daily sessions. While recent studies have demonstrated that a once daily 6-hr bout of EE confers benefits comparable to continuous EE, breaking the therapy into two shorter sessions may increase novelty and ultimately enhance recovery. Hence, the aim of the study was to test the hypothesis that functional and histological outcomes will be significantly improved by daily preclinical neurorehabilitation consisting of two 3-hr periods of EE vs. a single 6-hr session. Anesthetized adult male rats received a controlled cortical impact of moderate-to-severe injury (2.8mm tissue deformation at 4m/s) or sham surgery and were then randomly assigned to groups receiving standard (STD) housing, a single 6-hr session of EE, or two 3-hr sessions of EE daily for 3weeks. Motor function (beam-balance/traversal) and acquisition of spatial learning/memory retention (Morris water maze) were assessed on post-operative days 1-5 and 14-19, respectively. Cortical lesion volume was quantified on day 21. Both EE conditions improved motor function and acquisition of spatial learning, and reduced cortical lesion volume relative to STD housing (p<0.05), but did not differ from one another in any endpoint (p>0.05). The findings replicate previous work showing that 6-hr of EE daily is sufficient to confer behavioral and histological benefits after TBI and extend the findings by demonstrating that the benefits are comparable regardless of how the 6-hrs of EE are accrued. The relevance of the finding is that it can be extrapolated to the clinic and may benefit patients who cannot endure a single extended period of neurorehabilitation.