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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Brain median sagittal section showing the fluorescent dye DiI-lableling of transplanted neural cells via corpus callosum a successful migration from the (A) injection site to the (B) traumatic cold brain injury (TBI) site. (C) Confocal microscopic images of the TBI lesion at 2, 4, and 6 weeks following cell transplantation demonstrated double-labeling of injected cells with the neuronal nuclei (NeuN) neural marker and the glial fibrillary acidic protein (GFAP) astrocytic marker. DiI-positive cells (red) in the TBI lesion were co-stained with the NeuN neuronal or GFAP astrocytic (green) markers and merged as yellow.
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f5-etm-0-0-3527: Brain median sagittal section showing the fluorescent dye DiI-lableling of transplanted neural cells via corpus callosum a successful migration from the (A) injection site to the (B) traumatic cold brain injury (TBI) site. (C) Confocal microscopic images of the TBI lesion at 2, 4, and 6 weeks following cell transplantation demonstrated double-labeling of injected cells with the neuronal nuclei (NeuN) neural marker and the glial fibrillary acidic protein (GFAP) astrocytic marker. DiI-positive cells (red) in the TBI lesion were co-stained with the NeuN neuronal or GFAP astrocytic (green) markers and merged as yellow.

Mentions: DiI pre-labeled neuronal or glia were observed at the injection site and surrounding areas of TBI injury 2, 4 and 6 weeks post-transplantation. In NC-G, DiI-positive cells exhibited immunoreactivity for the NeuN neuronal marker and substantial co-expression, as shown in Fig. 5; however these cells did not exhibit immunoreactivity for GFAP. In GC-G, the pre-labeled glia were immunoreactive for the GFAP astrocytic marker but did not exhibit immunoreactivity for NeuN. These results demonstrated that the transplanted neurons and glia, although small in population, successfully migrated from the transplant site to the TBI lesion and differentiated into neural cells in vivo following TBI.


Comparative effect of immature neuronal or glial cell transplantation on motor functional recovery following experimental traumatic brain injury in rats
Brain median sagittal section showing the fluorescent dye DiI-lableling of transplanted neural cells via corpus callosum a successful migration from the (A) injection site to the (B) traumatic cold brain injury (TBI) site. (C) Confocal microscopic images of the TBI lesion at 2, 4, and 6 weeks following cell transplantation demonstrated double-labeling of injected cells with the neuronal nuclei (NeuN) neural marker and the glial fibrillary acidic protein (GFAP) astrocytic marker. DiI-positive cells (red) in the TBI lesion were co-stained with the NeuN neuronal or GFAP astrocytic (green) markers and merged as yellow.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998226&req=5

f5-etm-0-0-3527: Brain median sagittal section showing the fluorescent dye DiI-lableling of transplanted neural cells via corpus callosum a successful migration from the (A) injection site to the (B) traumatic cold brain injury (TBI) site. (C) Confocal microscopic images of the TBI lesion at 2, 4, and 6 weeks following cell transplantation demonstrated double-labeling of injected cells with the neuronal nuclei (NeuN) neural marker and the glial fibrillary acidic protein (GFAP) astrocytic marker. DiI-positive cells (red) in the TBI lesion were co-stained with the NeuN neuronal or GFAP astrocytic (green) markers and merged as yellow.
Mentions: DiI pre-labeled neuronal or glia were observed at the injection site and surrounding areas of TBI injury 2, 4 and 6 weeks post-transplantation. In NC-G, DiI-positive cells exhibited immunoreactivity for the NeuN neuronal marker and substantial co-expression, as shown in Fig. 5; however these cells did not exhibit immunoreactivity for GFAP. In GC-G, the pre-labeled glia were immunoreactive for the GFAP astrocytic marker but did not exhibit immunoreactivity for NeuN. These results demonstrated that the transplanted neurons and glia, although small in population, successfully migrated from the transplant site to the TBI lesion and differentiated into neural cells in vivo following TBI.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus