Recovery Of Motor Function In Rats Research Articles

Retracted: Study of Effect of Salvianolic Acid B on Motor Function Recovery in Rats with Spinal Cord Injury.

[This retracts the article DOI: 10.1155/2014/931850.].

Nischarin-siRNA delivered by polyethylenimine-alginate nanoparticles accelerates motor function recovery after spinal cord injury.

A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2a cells and primary cortical neurons. In recent years, more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury. We proposed that small interfering RNA targeting nischarin (Nis-siRNA) delivered by polyethyleneimine-alginate (PEI-ALG) nanoparticles promoted motor function recovery in rats with spinal cord injury. Direct microinjection of 5 μL PEI-ALG/Nis-siRNA into the spinal cord lesion area of spinal cord injury rats was performed. From day 7 after surgery, Basso, Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-siRNA group compared with the spinal cord injury group and PEI-ALG/Control-siRNA group. On day 21 after injection, hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-siRNA group. Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-siRNA group. These findings suggest that a complex of PEI-ALG nanoparticles and Nis-siRNA effectively suppresses nischarin expression, induces expression of growth-associated protein-43, and accelerates motor function recovery after spinal cord injury.

Effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration after spinal cord injury in rats.

[Purpose] The aim of this study was to evaluate the effect of oscillating electrical field stimulation on motor function recovery and myelin regeneration in rats with spinal cord injury. [Subjects and Methods] A rat model of spinal cord injury was constructed by using the Allen weight-drop method. These rats were randomly divided into normal, spinal cord injury, and spinal cord injury + oscillating electrical field stimulation groups. The experimental group received the intervention with oscillating electrical field stimulation, and the control group received the intervention with an electrical field stimulator without oscillating electrical field stimulation. Each group was then randomly divided into seven subgroups according to observation time (1, 2, 4, 6, 8, 10, and 12 weeks). Basso-Beattie-Bresnahan score and inclined plate test score evaluation, motor evoked potential detection, and histological observation were performed. [Results] In the first 2 weeks of oscillating electrical field stimulation, the oscillating electrical field stimulation and inclined plate test scores of spinal cord injury group and spinal cord injury + oscillating electrical field stimulation group were not significantly different. In the fourth week, the scores of the spinal cord injury group were significantly lower than those of the spinal cord injury + oscillating electrical field stimulation group. The motor evoked potential incubation period in the spinal cord injury + oscillating electrical field stimulation group at the various time points was shorter than that in the spinal cord injury group. In the sixth week, the relative area of myelin in the spinal cord injury + oscillating electrical field stimulation group was evidently larger than that in the spinal cord injury group. [Conclusion] Oscillating electrical field stimulation could effectively improve spinal cord conduction function and promote motor function recovery in rats with spinal cord injury, as well as promote myelin regeneration.

Oscillating field stimulation promotes recovery after spinal cord injury in rats: Assessment using behavioral, electrophysiological and histological evaluations.

We explored whether oscillating field stimulation (OFS) could efficiently promote motor function recovery in rat model of spinal cord injury. SD rats with spinal cord injury induced by Allen method was divided into two groups, experimental group rats received active stimulator units and control group rats received sham (inoperative) stimulator units. The electric field intensity was 600μV/mm, and the polarity alternated every 15 min. The results showed that the experimental group rats had significantly better locomotor function recovery (inclined-plane testing and modified Tarlov motor grading scale) 5 weeks after the injury (P<;0.05). OFS treatment significantly decreased motor evoked potential (MEP) latency differences and amplitude differences 4 w and 8 w post injury (P<;0.05, P<;0.01). Furthermore, the number of axons was quantified by immunofluorescence staining of nerve fiber (NF), increased axon numbers were observed at 4 w and 8 w in experimental group (P<;0.05). These findings suggest OFS can promote motor function recovery in SCI rats, and this effect may be related to the improving axon regeneration in spinal cord.

Effects of acupuncture based on myofascial meridian-based acupoint-selection on nerve regeneration and motor function recovery in rats with cerebral palsy

Effects of acupuncture based on myofascial meridian-based acupoint-selection on nerve regeneration and motor function recovery in rats with cerebral palsy

Exercise promotes motor functional recovery in rats with corticospinal tract injury: anti-apoptosis mechanism.

Studies have shown that exercise interventions can improve functional recovery after spinal cord injury, but the mechanism of action remains unclear. To investigate the mechanism, we established a unilateral corticospinal tract injury model in rats by pyramidotomy, and used a single pellet reaching task and horizontal ladder walking task as exercise interventions postoperatively. Functional recovery of forelimbs and forepaws in the rat models was noticeably enhanced after the exercises. Furthermore, TUNEL staining revealed significantly fewer apoptotic cells in the spinal cord of exercised rats, and western blot analysis showed that spinal cord expression of the apoptosis-related protein caspase-3 was significantly lower, and the expression of Bcl-2 was significantly higher, while the expression of Bax was not signifiantly changed after exercise, compared with the non-exercised group. Expression of these proteins decreased with time after injury, towards the levels observed in sham-operated rats, however at 4 weeks postoperatively, caspase-3 expression remained significantly greater than in sham-operated rats. The present findings indicate that a reduction in apoptosis is one of the mechanisms underlying the improvement of functional recovery by exercise interventions after corticospinal tract injury.

Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway.

The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guidance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord injury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, caspase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental findings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.

Study of effect of salvianolic acid B on motor function recovery in rats with spinal cord injury.

In this study effect of salvianolic acid B was observed on motor function recovery of rats with spinal cord injury. 50 rats were selected and after inducing SCI their recovery under controlled conditions was studied using Sal B and PBS (as control). Both compounds were introduced intraperitoneally in respective groups of traumatic rats at the same time intervals for 28 days. It was observed that Sal B introduced at 5 mg/kg/day resulted in better motor function recovery. BBB score was recorded which increased significantly along with the reduction in cavity area observed by bright field microscopy of tissues, that is, from 1 to 10 and from 0.20 ± 0.05 mm2 to 0.10 ± 0.03 mm2, in Sal B treated group, respectively, compared to PBS group. Statistical analysis was carried out using SPSS software (SPSS, Chicago, IL, USA), values were expressed as mean ± SEM, and P value <0.01 was considered significant. Effect of Sal B on expression of NF-kB p65 and IkBα was studied and OD values of densitometry of western blots were taken. MPO activity was also studied. It was observed that treatment of Sal B significantly reduced the expression of both compounds in Sal B treated group as compared to control group after 28 days of treatment.

Transplantation of differentiated bone marrow stromal cells promotes motor functional recovery in rats with stroke

Objective: To investigate the effects of transplantation into rats with stroke of bone marrow-derived mesenchymal stem cells (MSCs) induced by brain-derived neurotrophic factor (BDNF). Materials and methods: MSCs were harvested from 6-week-old Sprague–Dawley male rats, and transplanted into adult Sprague–Dawley male rats with transient middle cerebral artery occlusion. At 48 hours after stroke, the adult rats, weighing 250–280 g, were injected via the tail vein with 1×107 MSCs or MSCs induced by BDNF (BDNF-MSCs) suspended in 1 ml phosphate-buffered saline. All animals underwent the neurological function test for 14 days. Infarct volume and blood–brain barrier permeability assay were assessed on day 14 post-middle cerebral artery occlusion. Western blotting and immunohistochemical staining were used to detect the protein expression of neuron-specific enolase (NSE). Results: Both BDNF-MSCs and MSCs produced improvement in neurological deficits compared with vehicle controls on day 14 (P<0·05). In particular, the group transplanted with BDNF-MSCs exhibited significant recovery of motor function compared with the group transplanted with MSCs alone (P<0·05). Both BDNF-MSCs and MSCs, but particularly the former, reduced infarct volume, improved blood–brain barrier dysfunction, reduced serum NSE levels, activated the NSE activity, and inhibited neuronal apoptosis in the ischemic boundary zone. Conclusions: BDNF-MSCs might contribute to the motor function improvement partly by reducing neuronal damage via upregulating the NSE expression level and inhibiting neuronal apoptosis.

Omentum-Wrapped Scaffold with Longitudinally Oriented Micro-Channels Promotes Axonal Regeneration and Motor Functional Recovery in Rats

BackgroundTissue-engineered nerve scaffolds hold great potential in bridging large peripheral nerve defects. However, insufficient vascularization of nerve scaffolds limited neural tissues survival and regeneration, which hampered the successful implantation and clinical application of nerve scaffolds. The omentum possesses a high vascularization capacity and enhances regeneration and maturation of tissues and constructs to which it is applied. However, combined application of nerve scaffolds and omentum on axonal regeneration and functional recovery in the treatment of large peripheral nerve defects has rarely been investigated thus far.MethodsIn the present study, an omentum-wrapped collagen-chitosan scaffold was used to bridge a 15-mm-long sciatic nerve defect in rats. Rats that received nerve autografts or scaffolds alone were served as positive control or negative control, respectively. The axonal regeneration and functional recovery were examined by a combination of walking track analysis, electrophysiological assessment, Fluoro-Gold (FG) retrograde tracing, as well as morphometric analyses to both regenerated nerves and target muscles.FindingsThe results demonstrated that axonal regeneration and functional recovery were in the similar range between the omentum-wrapping group and the autograft group, which were significantly better than those in the scaffold alone group. Further investigation showed that the protein levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were significantly higher in the omentum-wrapping group than those in the scaffold alone group in the early weeks after surgery.ConclusionThese findings indicate that the omentum-wrapped scaffold is capable of enhancing axonal regeneration and functional recovery, which might be served as a potent alternative to nerve autografts. The beneficial effect of omentum-wrapping on nerve regeneration might be related with the proteins produced by omentum.

Granulocyte colony-stimulating factor enhances cellular proliferation and motor function recovery on rats subjected to traumatic brain injury

Objective: Traumatic brain injury (TBI) results in neurological dysfunction and death through primary or secondary mechanisms. Here, we evaluated the effect of osmotic pump delivery of granulocyte colony-stimulating factor (G-CSF) on the histopathology and motor function recovery of rats after experimental TBI.Methods: Sprague–Dawley rats were used as experimental model by fluid percussion device to cause brain injury on the motor cortex area. The rats were simultaneously subjected to TBI and were implanted of min-osmotic pump containing recombinant human G-CSF (300 μg/700 μl) via intraperitoneal injection. Motor function was assessed by rotarod test. 5-bromo-2'-deoxyuridine (BrdU) was used to label the proliferating cells and their differentiation was evaluated by histology and immunohistochemistry.Results: The G-CSF group showed significantly better motor function recovery than the control group, and the effect lasted up to 14 days after TBI. Moreover, the G-CSF group exhibited a greater increase in the number of BrdU-positive cells compared with the control group. The G-CSF group also had a significantly higher number of DCX-positive cells in the ipsilateral subventricular zone (SVZ) than the control group.Conclusions: These data suggest that the beneficial effect of delivering G-CSF via an osmotic pump may improve the motor function and enhance neurogenesis in the SVZ of the injured brain.

The effects of citicoline combined with rehabilitative training on neural plasticity after focal cerebral ischemia

Objective To investigate the effects of citicoline combined with rehabilitative training on motor function after focal cerebral ischemia. Methods One hundred and twenty male adult Sprague-Dawley rats ( 3 months old) were subjected to left middle cerebral artery occlusion (MCAO) by suturing. Ninety-six of them were randomly divided into four groups of 24: a control group, a drug group, a rehabilitative training group, and a drug combined with rehabilitative training group. The rats in the control group did not receive any treatment. Three days after reperfusion, those in the drug group received 500 mg/kg of citicoline daily; those in the rehabilitative training group received motor training including balancing, grasping, rotating and walking exercises; those in the combined group received both citicoline and the motor training program. Behavioral tests were administered at the 7th, 14th and 21st days after MCAO. At the same time points, immunohistochemistry was used to detect calcium-binding protein S100 and β-tubulin expression in the peri-ischemia region of the cortex. Results ①As compared with the control group, the drug group at the 7th, 14th and 21st day after MCAO and the other two groups at the 7th day after MCAO showed no significant difference in average behavior scores. But at the 14th and 21st day the rehabilitative training group as well as the drug combined with rehabilitative training group had average behavior scores significantly superior to those of the control group, especially in the drug combined with rehabilitative training group. ②As compared with the control group, the expression of S100 and β-tubulin in the drug and rehabilitative training groups at the 7th day after MCAO showed no significant difference. In the drug combined with rehabilitative training group the average score was significantly higher than in the other groups at the 7th day after MCAO. All the other groups had average scores significantly higher than that of the controls at the 14th and 21st day after MCAO, especially the drug combined with rehabilitative training group. Conclusions Citicoline combined with rehabilitative training can significantly improve motor function recovery in rats. The effect of the combined modalities was more obvious, and the functional enhancement might be partially attributable to the up-regulation of S100 and β-tubulin in the cortex. Key words: Cerebral ischemia; Citicoline; Rehabilitative training; Calcium-binding protein; β-tubulin

Immune therapy with cultured microglia grafting into the injured spinal cord promoting the recovery of rat's hind limb motor function

To study the effect of activated microglia grafting on rats' hind limb motor function recovery after spinal cord injury. Microglia were separated from primary culture and subcultured for 3 generations. Lipopolysaccharide was added to the culture medium with the terminal concentration of 10 microl/L for microglia activation 3 days before transplantation. Totally 80 adult Wistar rats were divided into transplantation group and control group, with 40 rats in each group. Spinal cord injury model of rats was set by hitting onto the spinal cord using a modified Allen impactor. With a 5 microl micro-syringe, the activated microglia suspension was injected into the injured area 7 days after the first operation. Basso, Beattie and Bresnahan (BBB) scoring for hind limb motor function was taken on the 1st, 7th, 14th, 21st, and 28th day after microglia transplantation, and 8 rats were sacrificed at each time point mentioned above, respectively. Frozen sections of the spinal cord were made for haematoxylin-eosin (HE) and Naoumenko-Feigin stainings. SPSS 11.0 software was used for statistical analysis. BBB scores for hind limb motor function on the 14th, 21st, and 28th day were significantly higher compared with the control group. Most liquefaction necrosis areas disappeared and only a few multicystic cavities surrounded by aggregated microglia remained in the transplantation group. Naoumenko-Feigin staining for microglia showed that the transplantation group had significantly more positive cells (P < 0.05). Grafting of activated microglia into the injured spinal cord can significantly promote the hind limb motor function recovery in rats with spinal cord injury and reduce the size of liquefaction necrosis area. The extent of lower limb motor function improvement has a positive correlation with the number of aggregated microglia.

Reversal of noradrenergic depletion and lipid peroxidation in the pons after brain injury correlates with motor function recovery in rats

Functional impairment after brain injury (BI) has been attributed to the inhibition of regions that are related to the injured site. Therefore, noradrenaline (NA) is thought to play a critical role in recovery from motor injury. However, the mechanism of this recovery process has not been completely elucidated. Moreover, the locus coeruleus (LC) projects from the pons through the rat sensorimotor cortex, and injury axotomizes LC fibers, depressing NA function. This was tested by measuring lipid peroxidation (LP) in the pons after sensorimotor cortex injury. Depression of function in the pons would be expected to alter areas receiving pontine efferents. Male Wistar rats were divided into three groups: control (n=16), injured (n=10) and recovering (n=16), and they were evaluated using a beam-walking assay between 2 and 20 days after cortical injury. We performed measures of NA and LP in both sides of the pons and cerebellum. We found a decrease of NA in the pons and the cerebellum, and a concomitant increase in the motor deficit and LP in the pons of injured animals. Recovering rats had NA and LP levels that were very similar to those observed in control rats. These observations suggest that the mechanism of remote inhibition after BI involves lipid peroxidation, and that the NA decrease found in the cerebellum of injured animals is mediated by a noradrenergic depression in the pons, or in areas receiving NA projections from the pons.

Recurrent paraplegia after remyelination of the spinal cord.

We have conducted a long-term study of spinal cord morphology and motor function recovery in rats that have undergone lumbar spinal demyelination induced by the B-fragment of cholera toxin (CTB)-saporin. We found that, after the initial demyelination and paraplegia, motor function recovered and was stable for up to 9 months, after which there occurred a slow deterioration of motor function accompanied by loss of motoneurons and loss of spinal white matter. A striking morphological feature was the appearance of large spheroids of calcium in the ventral and dorsal horns and occasionally in the white matter. Motor performance deterioration occurred earlier and was more severe in rats that had been exercised on a treadmill, but the same morphological changes occurred in both exercise- and nonexercise-treated animals. Rats given treadmill exercise starting 3 weeks after toxin injection had a mean motor deficit score of 3.0 (i.e., paraplegia) at perfusion, whereas the nontreadmill-treated rats had a mean score of 1.8 (SD 0.38; n = 6; P <.05). These findings suggest that, in addition to the acute effects of the toxin-induced demyelination from which there is recovery of motor function, there are chronic irreversible effects of the toxin, or the initial demyelination, that cause a slow progressive degeneration of the spinal cord. This model might therefore be useful in studying the long-term effects of spinal insult of the type associated with conditions such as postpolio syndrome.

Effects of electric stimulation and previous nerve injury on motor function recovery in rats

Effects of electric stimulation and previous nerve injury on motor function recovery in rats