The impact of enriched environment and transplantation of murine cortical embryonic stem cells on recovery from controlled cortical contusion injury

Purpose: The effectiveness of embryonic stem cell (eSC) therapy has been explored in many models of neurological disease and several research groups have shown that eSC treatment leads to improved outcomes in pre-clinical models of traumatic brain injury (TBI). Though functional recovery occurs, few surviving eSCs appear to develop neuronal characteristics; instead the majority of the surviving eSC express glial phenotypes. Additionally, researchers have shown that enriching the post-surgical environment of the subject promotes functional recovery following TBI. The purpose of the current project was to determine if post-surgical environmental enrichment (EE) impacts the survival, migration, and integration of eSCs in a rodent model of TBI and if the presence of these cells lead to improved outcomes. Methods: In the current study, the medial frontal cortex (MFC) of rats was injured using a controlled cortical impact (CCI) device. Immediately following injury the rats were placed into either EE or standard environment (SE) housing and then seven days post-injury rats received either murine cortical eSC or media. Behavioral testing consisted of the Morris water maze (MWM), Barnes Maze (BM), and Rotarod tasks (RR). Results: On the MWM task, TBI/eSC/EE animals performed as well as the Sham/SE and Sham/EE groups. The TBI/eSC/SE, TBI/Media/EE, and TBI/Media/SE groups were impaired compared to the controls. By the end of training on the BM there were no differences between the Sham, TBI/Media/EE, and TBI/eSC/EE groups. On the RR task all animals placed in the EE performed equally well and significantly better than their SE housed counterparts. By the end of training on the RR task, the TBI/eSC/EE group performed as well as the sham counterparts, and though not significant they also surpassed the performance of the injured animals that received enrichment or eSC treatment alone. Conclusions: Combing therapeutic strategies with enriching the post-injury environment is likely to be an important addition to determining the efficacy of pre-clinical therapies.