ABSTRACT
BACKGROUND:Studies have shown that neural stem cel transplantation combined with exercise training can promote the recovery of hindlimb motor function from spinal cord injury in rats, but its mechanism of action has not been fuly elucidated. OBJECTIVE:To investigate the effects of early exercise training combined with neural stem cel transplantation on the recovery of hindlimb motor function in rats with spinal cord injury. METHODS:Sixty Sprague-Dawley rats with spinal cord injury were randomly divided into three groups: control group (n=20, given conventional treatment after injury), cel transplantation group (n=20, given neural stem cel transplantation after injury), experimental group, (n=20, given neural stem cel transplantation combined with early exercise training after injury). Recovery of the hindlimb motor function was assessed by Basso, Beattie and Bresnahan scale and inclined plane test before and at 1, 7, 14, 21 days after injury. Western blot assay was used to detect caspase-3 and myeloperoxidase expression. Hematoxylin-eosin staining was done at 21 days after injury to observe the structure changes of the injured spinal cord. RESULTS AND CONCLUSION:(1) Scores of Basso, Beattie and Bresnahan scale and inclined plane test were significantly better in the experimental group than the cel transplantation group folowed by the control group (P < 0.05). (2) In the control group, the expression of caspase-3 and myeloperoxidase was significantly increased at 14 days after injury. In the cel transplantation, the expression of caspase-3 and myeloperoxidase was significantly higher than the experimental group (P < 0.05). (3) Pathological inflammation was reduced most in the experimental group folowed by the cel transplantation group. In the experimental group, the structure of injured spinal cord was improved and became relatively clear and intact. These findings indicate that neural stem cell transplantation combined with early exercise training can effectively promote the recovery of hindlimb motor function from spinal cord injury in rats, by reducing the expression of caspase-3 and myeloperoxidase and alleviating secondary lesion of the spinal cord.
ABSTRACT
BACKGROUND:Endothelial progenitor cels are widely used in the treatment of various vascular diseases, and early exercise training contributes to restore motor function after spinal cord injury. However, the therapeutic effects of endothelial progenitor cel transplantation or early exercise training alone are unfavorable. OBJECTIVE:To observe the influence of transplantation of endothelial progenitor cels combined with early exercise training on blood vessel regeneration and hind limb function in rats after spinal cord injury. METHODS:Eighty adult Sprague-Dawley rats were enroled to establish spinal cord injury models using the modified Alen’s method, and then randomly divided into four groups. Rats were respectively given culture mediumvia the tail vein, injection of endothelial progenitor cels (3×106)via the tail vein, roler and treadmil trainings for 2 weeks, or injection of endothelial progenitor celsvia the tail vein folowed by 2 weeks of roler and treadmil trainings in the model, cel transplantation, exercise and combined groups. RESULTS AND CONCLUSION:At 2 weeks after transplantation, the hindlimb motor function of rats in the combined group was better than that in the cel transplantation group and exercise group, and moreover, the percentage of CM-Dil positive cels, the number of horseradish peroxidase-positive nerve fibers, capilary density and expression of vascular endothelial growth factor and brain-derived neurotrophic factor were also significantly higher in the combined group than the cel transplantation group and exercise group. These findings indicate that early exercise training has a neuroprotective role in spinal cord injury; endothelial progenitor cel transplantation combined with early exercise training can promote regeneration of synapses and blood vessels and improve hindlimb motor function of rats, probably by increasing expression levels of vascular endothelial growth factor and brain-derived neurotrophic factor.
ABSTRACT
BACKGROUND:Electroacupuncture has promoting effects on the functional recovery of the injured spinal cord, can decrease pain, and elevate postoperative effect after acute spinal cord contusion.OBJECTIVE:To observe the effect of electroacupuncture on apoptosis in the injured site after spinal cord contusion, and analyze its neuroprotective effects on neurological function in rats with spinal cord contusion. METHODS:A total of 66 adult female Sprague-Dawley rats were randomly divided into: sham surgery group (n=20), spinal cord contusion group (n=20), electroacupuncture stimulation group (n=20) because six rats were excluded due to modeling failure and death. Before model establishment, at 1, 3 days, 1, 2, 3 and 4 weeks after model establishment, motor functions were evaluated by BBB score and the inclined plate test. At 3 days after model establishment, apoptosis of nerve cels could be detected in the site of injury in each experimental group using TUNEL assay. mRNA and protein expression of bax, bcl-2 and caspase-3 was detected surrounding the injury site using RT-PCR and western blot assay. Morphological changes in the site of injury could be observed using hematoxylin-eosin staining. The regeneration of nerve fibers was observed using HRP tracing. RESULTS AND CONCLUSION:(1) Motor function score was significantly increased at various time points in the 2nd week of treatment in the electroacupuncture stimulation group than in the spinal cord contusion group (P< 0.05). (2) Apoptotic index was significantly lower in the electroacupuncture stimulation group than in the spinal cord contusion group at 3 days after model establishment (P < 0.05). (3) mRNA and protein expression of bax and caspase-3 was significantly lower in the electroacupuncture stimulation group than in the spinal cord contusion group at 72 hours (P < 0.05); bcl-2 gene and protein expression was significantly higher (P < 0.05). (4) The number of HRP-positive nerve fibers was highest in the sham surgery group, folowed by electroacupuncture stimulation group, and lowest in the spinal cord contusion group at 4 weeks (P < 0.05). Results indicated that electroacupuncture plays a protective role on the spinal cord contusion by reducing apoptosis of nerve cels at the site of injury.
ABSTRACT
BACKGROUND:Neural stem cel transplantation alone has achieved unsatisfactory outcomes in the repair of damaged spinal cord tissues. To promote the survival, proliferation and neuronal differentiation of transplanted cels in vivo, it is necessary to further improve the micro-environment of spinal cord injury. OBJECTIVE:To investigate the effect of neural stem cel transplantation plus electroacupuncture on the hindlimb function and electrophysiological changes of rats with spinal cord injury. METHODS: Animal models of spinal cord injury were made in 72 Sprague-Dawley rats and randomized into four groups: control group with injection of culture mediumvia the tail vein; neural stem cel group with injection of neural stem cel suspensionvia the tail vein; electroacupuncture group given 1-week electroacupuncture atDu meridian and body points starting from 6 hours after modeling; combined group given injection of neural stem cel suspension via the tail vein+1-week electroacupuncture atDu meridian and body points starting from 6 hours after modeling. Motor functional recovery in rats was assessed by Basso-Beattie-Bresnahan score and inclined plane test before and at 1, 3 days and 1-4 weeks after modeling. At 4 weeks after modeling, hematoxylin-eosin staining was performed for pathological observation; fluorescence microscope was used to observe the survival and distribution of CM-Dil-labeled neural stem cels; horseradish peroxidase tracer was used to observe nerve fiber regeneration; rat neurophysiological recovery was assessed by determining motor evoked potentials and somatosensory evoked potentials. RESULTS AND CONCLUSION:At 2-4 weeks after modeling, the hindlimb function was better in the combined group than the neural stem cel group and electroacupuncture group; while it was better in the neural stem cel group and electroacupuncture group than the control group. At 4 weeks after modeling, there were few nerve axon-like structures and smal voids in the spinal cord of the neural stem cel group and electroacupuncture group; however, in the combined group, there were more nerve axon-like structures and no void in the spinal cord. At 4 weeks after modeling, the number of nerve fibers positive for CD-Dil and horseradish peroxidase was ranked as folows: combined group > neural stem cel group and electroacupuncture group > control group, and there were significant differences between groups (P < 0.05). The latencies of motor and somatosensory evoked potentials were significantly lower in the combined group than the neural stem cel group and electroaucpuncture group folowed by the control group (P < 0.05), whereas the amplitudes of motor and somatosensory evoked potentials were significantly higher in the combined group than the neural stem cel group and electroacupuncture group folowed by the control group (P < 0.05). In conclusion, these findings indicate that neural stem cel transplantation combined with electroacupuncture can promote synaptic regeneration and improve the motor and electrophysiological functions of rats.