Background Environmental enrichment (EE) enhances motor and cognitive performance after traumatic brain injury (TBI). However, whether the EE-mediated benefits are time-dependent and task-specific is unclear. A preliminary study, in which only half of the possible temporal manipulations were evaluated, revealed that the beneficial effects of enrichment were only observed when provided concurrently with specific training (i.e., motor or cognitive), suggesting task-specific dependence. Objective To further assess the effects of time of initiation and duration of EE on neurobehavioral recovery after TBI by evaluating and directly comparing all the temporal permutations. Methods Anesthetized adult male rats received either a cortical impact or sham injury and were then randomly assigned to eight groups receiving continuous, or early and delayed EE with either 1 or 2 weeks of exposure. Functional outcome was assessed with established motor (beam-balance/walk) and cognitive (Morris water maze) tests on post-injury days 1-5 and 14-18, respectively. Results Motor ability was enhanced in the TBI groups that received early EE (i.e., during testing) vs. standard housing. In contrast, acquisition of spatial learning was facilitated in the groups receiving delayed EE (i.e., during training). Conclusions These data support the conclusion from the previous study that EE-mediated functional improvement after TBI is contingent on task-specific neurobehavioral experience, and extends those preliminary findings by demonstrating that the duration of enriched exposure is also important for functional recovery.

Memory is fundamental to everyday life, and cognitive impairments resulting from traumatic brain injury (TBI) have devastating effects on TBI survivors. A contributing component to memory impairments caused by TBI are alterations in the neural circuits associated with memory function. In this review, we aim to bring together experimental findings that characterize behavioral memory deficits and the underlying pathophysiology of memory-involved circuits after TBI. While there is little doubt that TBI causes memory and cognitive dysfunction, it is difficult to conclude which memory phase i.e., encoding, maintenance or retrieval is specifically altered by TBI. This is most likely due to variation in behavioral protocols and experimental models. Additionally we review a selection of experimental treatments that hold translational potential to mitigate memory dysfunction following injury.

Environmental enrichment (EE) consistently induces marked benefits in male rats after traumatic brain injury (TBI), but whether similar efficacy extends to females is not well established. Hence, the aim of this study was to reassess the effect of EE on functional and histological outcome in female rats after brain trauma. Twenty-four normal cycling adult female rats underwent verification of estrous stage prior to controlled cortical impact (CCI) or sham injury and then were assigned to EE or standard (STD) housing. Motor function was assessed with beam-balance/beam-walk and rotarod tasks on post-operative days 1–5 and every other day from 1–19, respectively. Spatial learning/memory was evaluated in a Morris water maze on days 14–19. Morphologically intact hippocampal CA 1/3 cells and cortical lesion volume were quantified 3 weeks after injury. No differences were observed between the EE and STD sham groups in any endpoint measure and thus the data were pooled. In the TBI groups, EE improved beam-balance, beam-walk, rotarod, and spatial learning performance vs. STD (p’s < 0.05). EE also provided significant histological protection as confirmed by increased CA1/3 cell survival and decreased cortical lesion size vs. STD. These data demonstrate that EE confers robust benefits in female rats after CCI injury, which parallels numerous studies in males and lends further credence for EE as a preclinical model of neurorehabilitation.

Environmental enrichment (EE) confers significant benefits after experimental traumatic brain injury (TBI). In contrast, the antipsychotic drug (APD) haloperidol (HAL) exerts deleterious effects on neurobehavioral and cognitive recovery. Neurorehabilitation and management of agitation, however, are integral components of the treatment strategy for patients with TBI. Hence, the goal of this study was to determine how the two therapeutic approaches interact and influence motor and cognitive recovery. Anesthetized adult male rats received a controlled cortical impact (2.8 mm tissue deformation at 4 m/sec) or sham injury and then were provided HAL (0.5 mg/kg; intraperitoneally [IP]) or vehicle (VEH; 1 mL/kg; IP) commencing 24 h after surgery and once daily for 19 days while housed in EE or standard (STD) conditions. Beam balance/walk and Morris water maze performance were assessed on post-injury days 1-5 and 14-19, respectively, followed immediately by quantification of cortical lesion volumes. The data revealed both expected and unexpected findings. It was not surprising that the TBI groups receiving EE performed significantly better than those in STD housing and that the TBI + STD + HAL group performed worse than the TBI + STD + VEH group (p < 0.05). What was surprising was that the therapeutic effects of EE were greatly reduced by concomitant administration of HAL. No differences in cortical lesion volumes were observed among the groups (p > 0.05). The potential clinical implications of these findings suggest that administering HAL to patients undergoing neurorehabilitation may be a double-edged sword because agitation must be controlled before rehabilitation can be safely initiated and executed, but its use may compromise therapeutic efficacy.

Mild traumatic brain injury (mTBI) disrupts hippocampal function and can lead to long-lasting episodic memory impairments. The encoding of episodic memories relies on spatial information processing within the hippocampus. As the primary entry point for spatial information into the hippocampus, the dentate gyrus is thought to function as a physiological gate, or filter, of afferent excitation before reaching downstream area Cornu Ammonis (CA3). Although injury has previously been shown to alter dentate gyrus network excitability, it is unknown whether mTBI affects dentate gyrus output to area CA3. In this study, we assessed hippocampal function, specifically the interaction between the dentate gyrus and CA3, using behavioral and electrophysiological techniques in ex vivo brain slices 1 week following mild lateral fluid percussion injury (LFPI). Behaviorally, LFPI mice were found to be impaired in an object-place recognition task, indicating that spatial information processing in the hippocampus is disrupted. Extracellular recordings and voltage-sensitive dye imaging demonstrated that perforant path activation leads to the aberrant spread of excitation from the dentate gyrus into area CA3 along the mossy fiber pathway. These results suggest that after mTBI, the dentate gyrus has a diminished capacity to regulate cortical input into the hippocampus, leading to increased CA3 network excitability. The loss of the dentate filtering efficacy reveals a potential mechanism by which hippocampal-dependent spatial information processing is disrupted, and may contribute to memory dysfunction after mTBI.