Transplantation of neural stem cells enhances expression of synaptic protein and promotes functional recovery in a rat model of traumatic brain injury

Abstract

Abstract. Transplantion of neural stem cells (NSCs) hasshown promise for the treatment of traumatic brain injury (TBI). Although the functional mechanisms underlying transplant-mediated recovery following TBI have yet to be determined, previous studies demonstrated that transplanted NSCs may respond to the release of specific neurotransmitters, and/or the production of factors that promote neuronal growth. Therefore, we hypothesize that the direct transplantation of NSCs into the injured brain enhanced the expression of synaptic protein and regeneration-associated protein, which may be responsible for promoting functional recovery in a rat model of TBI. Our results showed that NSC transplant significantly improved neurological motor function in selected behavioral tests compared to saline control rats. Our data showed that the number of surviving cells engrafted into the rats was 4.1±0.9% of engrafted cells at 8 weeks post-transplantation, with 11.4±1.6% βⅢ-tubulin-immunopositive cells of these cells. RT-PCR and Western blot analysis demonstrated that the expression of synaptophysin (SYP) and regeneration-associated protein (GAP43) in the injured brain of NSC-transplanted rats was significantly increased compared to the saline control rats during the experimental period. These data suggest that NSCs transplanted directly into the injured brain are capable of surviving, differentiating into neurons and promoting functional recovery in a rat model of TBI. Engrafted NSCs increase the expression of SYP and GAP43 in the injured brain of NSC-transplanted rats, which is suggested as one of the mechanisms underlying the improved functional recovery on motor behavior due to the transplantation of NSCs following TBI.

Co-grafting of neural stem cells with olfactory en sheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism

“…It has been shown that transplanted NSCs can survive, differentiate into neurons and/or glia, and attenuate motor dysfunction after TBI [8,9]. These exciting advances in the stem cell field have boosted efforts to explore their therapeutic potential to ameliorate TBI deficits and efforts to elucidate their underlying molecular mechanism of action.…”

Cell Therapy for Brain Injury

“…Transplanted human NSCs have shown to produce glial derived neurotrophic factor (GDNF) resulting in axonal growth following fluid percussion TBI in rats [253]. Gene therapy such as the use of NGF transfection has also been explored to further augment the production of growth factors by modified stem cells being introduced into animal TBI models [241,[254][255][256][257].…”

Relevance of gap junctions and large pore channels in traumatic brain injury

“…Experiments in vivo and in vitro revealed that these beneficial effects were lacking, when gap junction communication was suppressed in the host (Jaderstad et al, 2010). Yu et al (2013) underlined these findings by showing that neuronal stem cell transplantation significantly enhanced the Cx43 protein expression in a rat model of controlled cortical impact TBI (Ma et al, 2011). Connexin43 expression after transplantation was increased in the core and the border of injury.…”