Refining environmental enrichment to advance rehabilitation based research after experimental traumatic brain injury

Abstract

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 (2.8 mm 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 3 weeks. 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.

Aripiprazole and environmental enrichment independently improve functional outcome after cortical impact injury in adult male rats, but their combination does not yield additional benefits

“…ARIP, unlike haloperidol, has no D 2 antagonist effects, but instead functions as a partial D 2 and 5-HT 1A receptor agonist (Burris et al, 2002;Wood and Reavill, 2007;Tanahashi et al, 2012). The hypothesis was that ARIP would confer cognitive benefits when provided alone, as previously shown (Phelps et al, 2017), but the benefits would be further enhanced when combined with EE, a preclinical model of neurorehabilitation (Kline et al, 2010;Bondi et al, 2014bBondi et al, , 2015Radabaugh et al, 2017).…”

“…It has been speculated in the past that the robust benefits consistently achieved with continuous EE provides a floor effect that limits recovery beyond a certain threshold. To remedy this potential discrepancy and to optimize EE as a viable preclinical model of neurorehabilitation, we have begun to delay the administration and limit the amount of EE provided to rats after TBI (Matter et al, 2011;de Witt et al, 2011;Radabaugh et al, 2016Radabaugh et al, , 2017Lajud et al, 2018). An interesting and informative future direction would be to evaluate ARIP combined with the optimized (i.e., more clinically relevant) EE paradigm to determine if an additive effect may emerge.…”

“…Controlled cortical impact (CCI) injury was produced as previously described (Kline at al., 2002a(Kline at al., ,b, 2010Bondi et al, 2014a;Radabaugh et al, 2017). Briefly, surgical anesthesia was induced and maintained with 4% and 2% concentrations of isoflurane, respectively, in 2:1 N 2 O:O 2 .…”

Enriched Physical Environment Attenuates Spatial and Social Memory Impairments of Aged Socially Isolated Mice

“…This nurturing environment is demonstrated to improve social ability, spatial cognition, and brain plasticity in healthy animals ( Fares et al, 2013 ; Hannan, 2014 ; Garthe et al, 2016 ). EE also exerts positive effects on various animal models of neurological disorders including AD ( Wolf et al, 2006 ; Salmin et al, 2017 ), Parkinson’s disease ( Hilario et al, 2016 ), stroke ( Livingston-Thomas et al, 2016 ), traumatic brain injury ( Radabaugh et al, 2017 ), and Huntington’s disease ( Skillings et al, 2014 ). EE includes not only physical factors, such as exercise and sensorial and visual stimulations, but also improved social interaction between individuals ( Van Praag et al, 2000 ; Nithianantharajah and Hannan, 2006 ).…”

Cognition and Intervention in Traumatic Brain Injury

“…For example, in an experimental laboratory setting it was observed that 6-hours of environmental enrichment provision on a daily basis was effective in conferring neurobehavioral and histological amelioration following TBI with extended improvements through the realization that the acquired benefits were comparable despite the manner in which the 6-hours of enriched environment were accrued [20]. The development of coping strategies for thriving and disorder adaptation, as well as the psychological adaptation to stressors and serious life events, have been discover to exert a marked influence on the progressive improvement and against the persistence of posttraumatic injury complaints.…”