Article type: Research Article
Authors: Shear, Deborah A.; ; | Tate, Ciara C. | Tate, Matthew C. | Archer, David R. | LaPlaca, Michelle C. | Stein, Donald G.; | Dunbar, Gary L.;
Affiliations: Department of Emergency Medicine, Emory University, Atlanta, GA, USA | Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, GA, USA | School of Medicine, Emory University, Atlanta, GA, USA | Department of Pediatrics, Emory University, Atlanta, GA, USA | Department of Neurology, Emory University, Atlanta, GA, USA | Field Neurosciences Institute, Saginaw, MI, USA | Neuroscience Program, Department of Psychology, Central Michigan University, Mount Pleasant, MI, USA
Note: [] Corresponding author: Deborah Shear, Ph.D., Walter Reed Army Institute of Research, MRMC-UWI-C; Bldng 503-2 W14, Silver Spring, MD 20910 Tel.: (301) 319-7208, Fax: (301) 319-9905; E-mail: [email protected]
Abstract: Purpose: Recent work indicates that transplanted neural stem cells (NSCs) can survive, migrate to the injury site, and facilitate recovery from traumatic brain injury (TBI). The present study manipulated timing and location of NSC transplants following controlled cortical impact injury (CCI) in mice to determine optimal transplant conditions. Methods: In Experiment 1 (timing), NSCs (E14.5 mouse) were injected into the host striatum, ipsilateral to the injury, at 2, 7, or 14 days. In Experiment 2 (location), NSCs or vehicle were injected into the mouse striatum (7 days post-CCI) either ipsilateral or contralateral to the injury and cognitive and motor abilities were assessed from weeks 1–8 post-transplant. Histological measures of NSC survival, migration, and differentiation were taken at 6 and 8 weeks post-transplant. Results: The results demonstrate that: (1) 2–7 days post-injury is the optimal time-range for delivering NSCs; (2) time of transplantation does not affect short-term phenotypic differentiation; (3) transplant location affects survival, migration, phenotype, and functional efficacy; and (4) NSC-mediated functional recovery is not contingent upon NSC migration or phenotypic differentiation. Conclusions: These findings provide further support for the idea that mechanisms other than the replacement of damaged neurons or glia, such as NSC-induced increases in protective neurotrophic factors, may be responsible for the functional recovery observed in this model of TBI.
Keywords: neural stem cells, traumatic brain injury, motor recovery, spatial learning and memory, stem cell survival and migration, CNS repair
DOI: 10.3233/RNN-2011-0593
Journal: Restorative Neurology and Neuroscience, vol. 29, no. 4, pp. 215-225, 2011
