Neural Stem Cells Over-Expressing Brain-Derived Neurotrophic Factor (BDNF) Stimulate Synaptic Protein Expression and Promote Functional Recovery Following Transplantation in Rat Model of Traumatic Brain Injury

Brain-derived neurotrophic factor (BDNF) plays an essential regulatory role in the survival and differentiation of various neural cell types during brain development and after injury. In this study, we used neural stem cells (NSCs) genetically modified to encode BDNF gene (BDNF/NSCs) and naive NSCs transplantation and found that BDNF/NSCs significantly improved neurological motor function following traumatic brain injury (TBI) on selected behavioral tests. Our data clearly demonstrate that the transplantation of BDNF/NSCs causes overexpression of BDNF in the brains of TBI rats. The number of surviving engrafted cells and the proportion of engrafted cells with a neuronal phenotype were significantly greater in BDNF/NSCs than in naive NSCs-transplanted rats. The expression of pre- and post-synaptic proteins and a regeneration-associated gene in the BDNF/NSCs-transplanted rats was significantly increased compared to that in NSCs-transplanted rats, especially at the early stage of post-transplantation. These data suggest that neurite growth and overexpression of synaptic proteins in BDNF/NSC-stransplanted rats are associated with the overexpression of BDNF, which is hypothesized to be one of the mechanisms underlying the improved functional recovery in motor behavior at the early stage of cell transplantation following TBI. Therefore, the protective effect of the BDNF-modified NSCs transplantation is greater than that of the naive NSCs transplantation.