Abbreviated Environmental Enrichment Enhances Neurobehavioral Recovery Comparably to Continuous Exposure After Traumatic Brain Injury

Abstract

Background Environmental enrichment (EE) is a complex living milieu that has been shown to enhance functional recovery vs. standard (STD) housing after experimental traumatic brain injury (TBI) and therefore may be considered a rodent correlate of rehabilitation. However, the typical EE paradigm consists of continuous exposure to enrichment after TBI, which is inconsistent with the limited time frame in clinical rehabilitation. Objective To determine whether abbreviated EE (i.e., rehabilitation-relevant dose response) confers benefits similar to typical EE after TBI. Methods Adult male rats received either a controlled cortical impact (2.8 mm depth at 4 m/sec) or sham injury and were then randomly assigned to TBI + EE, TBI + EE (2hr), TBI + EE (4hr), TBI + EE (6hr), TBI + STD, and respective sham controls. Motor (beam-balance/beam-walk; BB/BW) and cognitive (Morris water maze; MWM) performance was assessed on post-operative days 1-5 and 14-19, respectively. Results The TBI + EE (2hr) and TBI + EE (4hr) groups were not statistically different from the TBI + STD group in any behavioral assessment. In contrast, the TBI + EE (6hr) group exhibited significant enhancement of motor and cognitive performance vs. the TBI + STD group, as well as the TBI + EE (2hr) and TBI + EE (4hr) groups (p < 0.003), and did not differ from the TBI + EE (typical) group. Conclusions These data demonstrate that abbreviated EE (6hr) produces motor and cognitive benefits similar to continuous EE after TBI and thus may be considered a dose-relevant rehabilitation paradigm.

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.…”

“…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.…”

Evaluation of a Combined Treatment Paradigm Consisting of Environmental Enrichment and the 5-HT1A Receptor Agonist Buspirone after Experimental Traumatic Brain Injury

“…The workshop leaders focused exclusively on the potential for combinatorial pharmacological agents to promote recovery. While this is a commendable start, there is certainly real potential and value in including non-invasive therapies, such as environmental enrichment (EE) or exercise (Gomez-Pinilla et al, 2011;Griesbach et al, 2009;Hamm et al, 1996;Hicks et al, 2002;Hoffman et al, 2008;Kline et al, 2007Kline et al, ,2010Matter et al, 2011;Passineau et al, 2001;de Witt et al, 2011), in combinational therapy paradigms for promoting recovery and perhaps augmenting the pharmacological effects, particularly in rehabilitation settings.…”

“…This paradigm has consistently shown improvements in behavioral and histological outcome after brain trauma and can therefore be considered a reasonable approach to preclinical rehabilitation. Importantly, the benefits conferred by EE span clinically-relevant models of experimental TBI, such as controlled cortical impact (CCI; Chen et al, 2005;de Witt et al, 2011;Hoffman et al, 2008;Kline et al, 2007Kline et al, ,2010Matter et al, 2011;Sozda et al, 2010) and fluid percussion (Hamm et al, 1996;Hicks et al, 2002;Gaulke et al, 2005;Giza et al, 2005;Maegele et al, 2005;Passineau et al, 2001). The second therapy in this combined treatment approach is the systemic administration of the serotonin 1A (5-HT 1A )-receptor agonist buspirone.…”