Comparative effect of immature neuronal or glial cell transplantation on motor functional recovery following experimental traumatic brain injury in rats

Abstract

The present study evaluated the comparative effect of stereotaxically transplanted immature neuronal or glial cells in brain on motor functional recovery and cytokine expression after cold-induced traumatic brain injury (TBI) in adult rats. A total of 60 rats were divided into four groups (n=15/group): Sham group; TBI only group; TBI plus neuronal cells-transplanted group (NC-G); and TBI plus glial cells-transplanted group (GC-G). Cortical lesions were induced by a touching metal stamp, frozen with liquid nitrogen, to the dura mater over the motor cortex of adult rats. Neuronal and glial cells were isolated from rat embryonic and newborn cortices, respectively, and cultured in culture flasks. Rats received neurons or glia grafts (~1×106 cells) 5 days after TBI was induced. Motor functional evaluation was performed with the rotarod test prior to and following glial and neural cell grafts. Five rats from each group were sacrificed at 2, 4 and 6 weeks post-cell transplantation. Immunofluorescence staining was performed on brain section to identify the transplanted neuronal or glial cells using neural and astrocytic markers. The expression levels of cytokines, including transforming growth factor-β, glial cell-derived neurotrophic factor and vascular endothelial growth factor, which have key roles in the proliferation, differentiation and survival of neural cells, were analyzed by immunohistochemistry and western blotting. A localized cortical lesion was evoked in all injured rats, resulting in significant motor deficits. Transplanted cells successfully migrated and survived in the injured brain lesion, and the expression of neuronal and astrocyte markers were detected in the NC-G and GC-G groups, respectively. Rats in the NC-G and GC-G cell-transplanted groups exhibited significant motor functional recovery and reduced histopathologic lesions, as compared with the TBI-G rats that did not receive neural cells (P<0.05, respectively). Furthermore, GC-G treatment induced significantly improved motor functional recovery, as compared with the NC-G group (P<0.05). Increased cytokine expression levels were detected in the NC-G and GC-G groups, as compared with the TBI-G; however, no differences were found between the two groups. These data suggested that transplanted immature neural cells may promote the survival of neural cells in cortical lesion and motor functional recovery. Furthermore, transplanted glial cells may be used as an effective therapeutic tool for TBI patients with abnormalities in motor functional recovery and cytokine expression.

Transplantation of mesenchymal stem cells genetically engineered to overexpress interleukin-10 promotes alternative inflammatory response in rat model of traumatic brain injury

“…One of the major causes of neurological damage and reduced functional outcome in TBI is due to the inflammatory response after injury. Following the initial injury, both pro- and anti-inflammatory cytokines are released, which initiate the infiltration of leukocytes and activate astrocytes and microglia to the injury site [3, 4]. The activation of such cells can be both beneficial and harmful to the outcome following TBI.…”

Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson’s disease model

“…Furthermore, evaluation of cell survival and function after transplantation is an important factor to determine the clinical effect. However, there is no clear judgment to show the preferential effect of skewed differentiation to neurons or glia since both cell types were applied in transplantation therapy (Quan et al 2016). As to the recovery of motor function, glial cells transplantation had more beneficial effects compared to the transplantation of neuronal cells according to the above mentioned study (Quan et al 2016).…”

“…However, there is no clear judgment to show the preferential effect of skewed differentiation to neurons or glia since both cell types were applied in transplantation therapy (Quan et al 2016). As to the recovery of motor function, glial cells transplantation had more beneficial effects compared to the transplantation of neuronal cells according to the above mentioned study (Quan et al 2016). The future work will elucidate the difference between transplantation of neuronal and glial cells generated from LiCl-treated NSCs.…”

Immunological Responses to Transgene-Modified Neural Stem Cells After Transplantation

“…NSCs and 293T cells were labeled with GFP. As a biomarker of brain injury, GFAP represents the degree of inflammatory injury at the transplantation site ( 25 , 27 ). As shown in Figures 5 and 9A , GFAP-positive cells were accumulated around and immersed at the transplantation site in all groups of rats on day 3 after transplantation; however, they had decreased significantly on day 21 after transplantation.…”

“…Astrocytes and microglial cells are critical executors in inflammatory and immunological responses ( 25 – 27 , 29 , 30 ). Astrocytes are responsible for repair following injury or damage and induce the elevated production of inflammatory factors, further activating these cells to migrate toward the injured sites ( 26 , 27 , 30 ). Our results indicated that the responses of astrocytes to NSC transplantation were derived from the transplantation procedure since similar changes were also observed at the transplantation site of rats in the control group given PBS injection alone.…”