Combining enriched environment and induced pluripotent stem cell therapy results in improved cognitive and motor function following traumatic brain injury
Affiliations: The Brain Research Laboratory, Saginaw Valley State University, University Center, MI, USA | Field Neuroscience Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI, USA
Note: [] Corresponding author: Jeffery S. Smith, Ph.D. The Malcolm and Lois Field Endowed Chair in Health Sciences, Department of Health Sciences, Crystal M. Lange College of Health & Human Services, Saginaw Valley State University, 7400 Bay Road, University Center, MI 48710, USA. Tel.: +1 989 964 4503; Fax: +1 989 964 4925; E-mail: jsmith12@svsu.edu
Abstract: Purpose: Despite advances towards potential clinically viable therapies there has been only limited success in improving functional recovery following traumatic brain injury (TBI). In rats, exposure to an enriched environment (EE) improves learning and fosters motor skill development. Induced pluripotent stem cells (iPSC) have been shown to survive transplantation and influence the recovery process. The current study evaluated EE and iPSC as a polytherapy for remediating cognitive deficits following medial frontal cortex (mFC) controlled cortical impact (CCI) injury. Methods: Sixty adult male rats received a midline mFC CCI or sham injury and were randomly placed in either EE or standard environment (SE). Seven days post-injury rats received bilateral transplantation of iPSCs or media. Behavioral measures were conducted throughout the remainder of the study. Following behavioral analysis, brains were extracted and prepared for histological analysis. Results: Open-field data revealed that combined therapy resulted in typical Sham/EE activity rearing patterns by the conclusion of the study. On the Vermicelli Handling task, rats with EE/iPSC polytherapy performed better than media-treated rats. Furthermore, rats treated with polytherapy performed equivalently to Sham/EE rats on the Morris water maze. Proficiency on the Rotarod was consistently better in EE when compared to SE counterparts. Confocal microscopy confirmed that iPSCs survived and migrated away from the transplantation site. Conclusions: Overall, EE or iPSC therapy improved cognition and motor performance, however, full cognitive restoration was seen only with the EE/iPSC treatment. These data suggest that EE/iPSC therapy should be explored as a potential, clinically relevant, treatment for TBI.
