A Relatively Brief Exposure to Environmental Enrichment after Experimental Traumatic Brain Injury Confers Long-Term Cognitive Benefits

Abstract

It is well established that a relatively brief exposure to environmental enrichment (EE) enhances motor and cognitive performance after experimental traumatic brain injury (TBI), but it is not known whether the benefits can be sustained after EE is discontinued. To address this important rehabilitation-relevant concern, anesthetized rats received a controlled cortical impact (CCI) or sham injury, and for phase 1 of the experiment were randomly assigned to either 3 weeks of EE or standard (STD) housing. Neurobehavioral outcome was assessed by established motor and cognitive tests on postoperative days 1-5 and 14-18, respectively. Beam-balance and spatial learning were facilitated in the TBI + EE more than the TBI + STD group ( p < 0.0001). In phase 2 of the experiment, half of the rats in EE were transferred to STD conditions (TBI + EE + STD and sham + EE + STD), and neurobehavior was re-assessed once per month for 6 months. The TBI + EE and TBI + EE + STD groups performed markedly better in the water maze than the TBI + STD group ( p < 0.0001), and did not differ from one another ( p = 0.53). These data replicate those of several studies from our laboratory showing that EE enhances recovery after CCI injury, and extend those findings by demonstrating that the cognitive benefits are maintained for at least 6 months post-rehabilitation. The persistent benefits shown with this paradigm provide further support for EE as a pre-clinical model of rehabilitation that can be further explored, either alone or in combination with pharmacotherapies, for optimal neurorehabilitation after TBI.

A Combined Therapeutic Regimen of Buspirone and Environmental Enrichment Is More Efficacious than Either Alone in Enhancing Spatial Learning in Brain-Injured Pediatric Rats

“…The data revealed that the TBI group receiving EE plus vehicle (i.e., EE alone group) performed significantly better in the acquisition task in the MWM than the vehicle-treated STD housed group, which replicates numerous studies in adult models of TBI. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]36 EE alone, however, did not lead to an increase in memory retention, which is in contrast to that seen in adult models. 23,26,29,33 As reported for Experiment 1, the buspirone (0.1 mg/kg) STD-housed group was also significantly better than the STD vehicle group in the MWM.…”

“…[18][19][20][21][22][23][24][25][26] Likewise, EE has also been shown to confer neurobehavioral and histological benefits in adult male rats after CCI 20,23,[26][27][28][29][30][31][32][33][34] and fluid percussion brain injury. [35][36][37][38][39][40] Recently, the benefits of EE have also been extended to female rats after CCI.…”

“…In addition, to make the treatments even more clinically relevant, delayed and abbreviated EE studies should be incorporated into the experimental design as we have been doing in adult male and female rats after CCI injury. 28,[30][31][32] …”

“…Environmental enrichment (EE), in particular, has been evaluated extensively in adult, and to a much lesser extent, in pediatric rodents as a pre-clinical model of neurorehabilitation. EE consists of expansive accommodations, which include cognitive and social stimulation that results in the reduction of histological damage and enhancement of functional recovery 27 induced by either controlled cortical impact (CCI) 20,23,[26][27][28][29][30][31][32][33][34] or fluid percussion. [35][36][37][38][39][40] Given that the 5-HT 1A receptor agonist buspirone and EE confer recovery in adult rats after brain trauma, the goals of this study were to evaluate the potential efficacy of these therapies alone and in combination after pediatric TBI.…”

Old Dog, New Tricks: The Attentional Set-Shifting Test as a Novel Cognitive Behavioral Task after Controlled Cortical Impact Injury

“…All surgical procedures were performed as previously described. 10,11,13,[40][41][42][43][44] Briefly, isoflurane anesthesia was induced and maintained using a 2:1 N 2 O/O 2 gas mix at concentrations of 4% and 2%, respectively. Rats were subsequently intubated endotracheally, placed on mechanical ventilation for anesthesia maintenance, and secured in a stereotaxic frame.…”