Pre and post-injury environmental enrichment effects functional recovery following medial frontal cortical contusion injury in rats

Abstract

The rodent has been the preferred research model for evaluating the mechanisms related to, and potential treatments for, traumatic brain injury (TBI). Many therapies previously determined to be effective in pre-clinical investigations have failed to show the same effectiveness in clinical trials. The environment a rodent is housed in plays an important role in brain and behavioral development. Housing rodents in non-enriched environments significantly alters the development of the rodent brain and its behavioral profile, negatively impacting the ecological validity of the rodent model. This investigation employed 113 male Long-Evans rats assigned to either an enriched environment (EE) or standard environment (SE) from post-natal day 25. At four months of age, rats received either a controlled cortical impact (CCI) to the medial frontal cortex (mFC) or sham injury. Rats assigned to EE or SE pre-injury were re-assigned to remain in, or switch to, EE or SE post-injury. The open-field test (OFT), vermicelli handling test (VHT) Morris water maze (MWM), and rotor-rod (RR), were used to evaluate the animals response to TBI. The data from the current investigation indicates that the performance of TBI rats assigned to pre-injury EE was improved on the MWM compared to the TBI rats assigned to pre-injury SE. However, those that were reared in the EE performed better on the MWM if placed into a SE post-injury as compared to those placed into the EE after insult. The TBI and sham groups that were raised, and remained, in the SE performed worse than any of the EE groups on the RR. TBI rats that were placed in the EE had larger cortices and more cells in the hippocampus than the TBI rats housed in the SE. These data strongly suggest that the pre-injury housing environment should be considered as investigators refine pre-clinical models of TBI.