title: Combining enriched environment and induced pluripotent stem cell therapy results in improved cognitive and motor function following traumatic brain injury.
abstract: OBJECTIVE
  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.
authors: The Brain Research Laboratory, Saginaw Valley State University, University Center, MI, USA.
authors: Jacob
authors: J
authors: Dunkerson
authors: The Brain Research Laboratory, Saginaw Valley State University, University Center, MI, USA.
authors: Kasey E
authors: KE
authors: Moritz
authors: The Brain Research Laboratory, Saginaw Valley State University, University Center, MI, USA.
authors: Jennica
authors: J
authors: Young
authors: The Brain Research Laboratory, Saginaw Valley State University, University Center, MI, USA.
authors: Tim
authors: T
authors: Pionk
authors: Field Neuroscience Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI, USA.
authors: Kyle
authors: K
authors: Fink
authors: Field Neuroscience Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI, USA.
authors: Julien
authors: J
authors: Rossignol
authors: Field Neuroscience Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI, USA.
authors: Gary
authors: G
authors: Dunbar
authors: The Brain Research Laboratory, Saginaw Valley State University, University Center, MI, USA.
authors: Jeffrey S
authors: JS
authors: Smith
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications; D003072:Cognition Disorders / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D004777:Environment; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D057026:Induced Pluripotent Stem Cells / Q000502:physiology* / Q000637:transplantation*; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009069:Movement Disorders / Q000209:etiology / Q000628:therapy*; D053580:Muscle Strength / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010751:Phosphopyruvate Hydratase