Empirical Comparison of Typical and Atypical Environmental Enrichment Paradigms on Functional and Histological Outcome after Experimental Traumatic Brain Injury

Abstract

Several studies have shown that housing rats in an enriched environment (EE) after traumatic brain injury (TBI) improves functional and histological outcome. The typical EE includes exploratory, sensory, and social components in cages that are often vastly larger than standard (STD) housing. It is uncertain, however, whether a single or specific component is sufficient to confer these benefits after TBI, or if all, perhaps in an additive or synergistic manner, are necessary. To clarify this ambiguity, anesthetized adult male rats were subjected to either a controlled cortical impact or sham injury, and then were randomly assigned to five different housing paradigms: (1) EE (typical), (2) EE (-social), (3) EE (-stimuli), (4) STD (typical), and (5) STD (+stimuli). Motor and cognitive function were assessed using conventional motor (beam-balance/traversal) and cognitive (spatial learning in a Morris water maze) tests on postoperative days 1-5 and 14-19, respectively, and cortical lesion volume and CA1/CA3 cell loss were quantified at 3 weeks. No significant differences were observed among the sham groups in any comparison and thus their data were pooled (i.e., SHAM). In the TBI groups, typical EE improved beam-balance versus both STD (+stimuli) and EE (-social), it facilitated the acquisition of spatial learning and memory retention versus all other housing conditions (p < 0.003), and it reduced lesion volume and CA3 cell loss versus STD (typical) housing. While rats in the three atypical EE conditions exhibited slightly better cognitive performance and histological protection versus the typical STD group, the overall effects were not significant. These data suggest that exposing TBI rats to any of the three components individually may be more advantageous than no enrichment, but only exposure to typical EE yields optimal benefits.

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

“…After weaning (PND-28), the rats were placed in their respective assigned housing conditions. The EE consisted of specifically designed 36 · 30 · 20-inch stainless steel wire cages consisting of three levels and ladders to ambulate from one level to another such that interaction with the various toys (e.g., balls, blocks, and tubes), nesting materials (e.g., paper towels), cage mates, and ad libitum food and water would be achievable (for depiction of EE cage, see 20,29 ). To maintain novelty, the objects were rearranged every day and changed each time the cage was cleaned, which was twice per week.…”

“…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

“…Following surgery, and after the effects of anesthesia abated (as evidenced by spontaneous movement in the holding cage), the rats were returned to the colony where those designated for EE were immediately placed in specifically designed 36 · 30 · 20-inch steel-wire cages that consist of three levels with ladders to ambulate from one level to another, and contain various toys (e.g., balls, blocks, and tubes), nesting materials (e.g., paper towels), and ad libitum food and water (for depiction of the EE cage, see Kline et al, 2007 andSozda et al, 2010). To maintain novelty, the objects were rearranged every day and changed each time the cage was cleaned, which was twice per week.…”

“…To reduce counting errors associated with falsepositive identification of dying neurons, the total number of CA1 and CA3 morphologically-intact neurons (i.e., those with a clearly defined cell body and nucleus) were counted using a Nikon Eclipse E600 microscope with a 40 · objective. For consistency and replication, the data are presented as the percent of total neurons in the ipsilateral (injured) CA1 and CA3 regions relative to the contralateral (uninjured) hippocampus, as previously reported Dixon et al, 1999;Hoffman et al, 2008;Kline et al, 2004Kline et al, ,2010Sozda et al, 2010).…”

“…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.…”