Pre-operative environmental enrichment does not yield a prophylactic effect against traumatic brain injury-induced...

The robustness of environmental enrichment (EE) in ameliorating neurobehavioral and cognitive deficits after experimental traumatic brain injury (TBI) is unequivocal. What is equivocal is whether EE can function as a prophylactic to afford resiliency and neuroprotection against TBI. We hypothesized that pre-operative EE would yield a protective effect against TBI-induced motor, cognitive, and coping deficits, and that further improvements would be conferred when EE is provided before and after TBI. To test the hypotheses, adult male rats received either 4 weeks of EE or standard (STD) housing prior to undergoing a controlled cortical impact of moderate severity (2.8 mm deformation at 4 m/s) or sham injury while under anesthesia. After injury, the rats were randomly assigned to post-operative EE or STD housing. Motor ability, spatial learning, and memory retention were assessed by beam-walk and water maze tests, respectively. Active and passive behavioral coping strategies were evaluated with the shock probe defensive burying (SPDB) test. c-Fos and cortical lesion volume were also quantified. The post-TBI enrichment groups (EE + TBI + EE and STD + TBI + EE) did not differ (p > 0.05) and performed better than the post-TBI STD-housed groups (EE + TBI + STD and STD + TBI + STD) on motor and cognition (p < 0.05). The post-TBI STD groups did not differ, regardless of whether in EE or STD living conditions before injury (p > 0.05). Moreover, both post-TBI enrichment groups performed better in the SPDB test relative to the STD + TBI + STD group (p < 0.05). c-Fos + cells were upregulated in the ipsilateral CA₁ in both pre-injury EE groups relative to the pre-injury STD groups (p < 0.05). No statistical differences were observed in cortical lesion volume among the groups. Overall, these data do not support the hypothesis as no neuroprotective effect was observed with 4 weeks of pre-operative EE and no additional benefit was achieved in the TBI group receiving both pre-and-post EE relative to the TBI group receiving only post-EE. However, the data do reinforce the consistency of post-TBI EE in producing robust neurobehavioral benefits, which further supports this paradigm as a relevant preclinical model of neurorehabilitation.