Bresnahan Scale Research Articles

Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function.

BackgroundLatest studies show that low-energy extracorporeal shock wave therapy (ESWT) can upregulate levels of vascular endothelial growth factor (VEGF). VEGF can ease nervous tissue harm after spinal cord injury (SCI). This study aims to explore whether low-energy ESWT can promote expression of VEGF, protect nervous tissue after SCI, and improve motor function.MethodsNinety adult female rats were divided into the following groups: Group A (simple laminectomy), Group B (laminectomy and low-energy ESWT), Group C (spinal cord injury), and Group D (spinal cord injury and low-energy ESWT). Impinger was used to cause thoracic spinal cord injury. Low-energy ESWT was applied as treatment after injury three times a week, for 3 weeks. After SCI, the Basso, Beattie, and Bresnahan (BBB) scale was used to evaluate motor function over a period of 42 days at different time points. Hematoxylin and eosin (HE) staining was used to evaluate nerve tissue injury. Neuronal nuclear antigen (NeuN) staining was also used to evaluate loss of neurons. Polymerase chain reaction was used to detect messenger RNA (mRNA) expression of VEGF and its receptor fms-like tyrosine kinase 1 (Flt-1). Immunostaining was used to evaluate VEGF protein expression level in myeloid tissue.ResultsBBB scores of Groups A and B showed no significant result related to dyskinesia. HE and NeuN staining indicated that only using low-energy ESWT could not cause damage of nervous tissue in Group B. Recovery of motor function at 7, 35, and 42 days after SCI in Group D was better than that in Group C (P<0.05). Compared with Group C, number of NeuN-positive cells at 42 days after SCI increased significantly (P<0.05). The mRNA levels of VEGF and Flt-1 and VEGF expression at 7 days after SCI in Group D were significantly higher than those in Group C (P<0.05).ConclusionLow-energy ESWT promotes expression of VEGF, decreases secondary damage of nerve tissue, and improves recovery of motor function. It can be regarded as one mode of clinical routine adjunctive therapy for spinal injury.

Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury.

ObjectiveThe current study aimed to evaluate the contribution(s) of specific opioid receptor systems to the analgesic and detrimental effects of morphine, observed after spinal cord injury in prior studies.Study DesignWe used specific opioid receptor agonists to assess the effects of µ- (DAMGO), δ- (DPDPE), and κ- (GR89696) opioid receptor activation on locomotor (BBB, tapered beam, ladder tests) and sensory (girdle, tactile, and tail-flick tests) recovery in a rodent contusion model (T12). We also tested the contribution of non-classic opioid binding using [+]- morphine.MethodsFirst, a dose-response curve for analgesic efficacy was generated for each opioid agonist. Baseline locomotor and sensory reactivity was assessed 24 h after injury. Subjects were then treated with an intrathecal dose of a specific agonist and re-tested after 30 min. To evaluate effects on recovery, subjects were treated with a single dose of an agonist and both locomotor and sensory function were monitored for 21 d.ResultsAll agonists for the classic opioid receptors, but not the [+]- morphine enantiomer, produced antinociception at a concentration equivalent to a dose of morphine previously shown to produce strong analgesic effects (0.32 μmol). DAMGO and [+]- morphine did not affect long-term recovery. GR89696, however, significantly undermined recovery of locomotor function at all doses tested.ConclusionsBased on these data, we hypothesize that the analgesic efficacy of morphine is primarily mediated by binding to the classic μ-opioid receptor. Conversely, the adverse effects of morphine may be linked to activation of the κ-opioid receptor. Ultimately, elucidating the molecular mechanisms underlying the effects of morphine is imperative in order to develop safe and effective pharmacological interventions in a clinical setting.SettingUSA

Curcumin Attenuates Inflammation, Oxidative Stress, and Ultrastructural Damage Induced by Spinal Cord Ischemia–Reperfusion Injury in Rats

Curcumin is a molecule found in turmeric root that possesses anti-inflammatory and antioxidant properties and has been widely used to treat neurodegenerative diseases. We investigated whether curcumin stimulates the neurorepair process and improves locomotor function in a rat model of spinal cord ischemia-reperfusion injury. Thirty-two Wistar albino rats (190-220 g) were randomly allocated into 4 groups of 8 rats each: 1 sham-operated group and 3 ischemia-reperfusion injury groups that received intraperitoneal injections of saline vehicle, methylprednisolone (MP, 30 mg/kg following induction of ischemia-reperfusion [IR] injury), or curcumin (200 mg/kg for 7 days before induction of IR injury). Spinal cord IR injury was induced by occlusion of the abdominal aorta for 30 minutes. After 24 hours of reperfusion, locomotor function was assessed using the Basso, Beattie, and Bresnahan scale. All animals were sacrificed. Spinal cord tissues were harvested to evaluate histopathological and ultrastructural alterations and to analyze levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta, nitric oxide, and caspase-3, as well as enzyme activities of superoxide dismutase and glutathione peroxidase. Intraperitoneal administration of curcumin significantly reduced inflammatory cytokine expression, attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in comparison to treatment with MP or saline. Histopathological and ultrastructural abnormalities were significantly reduced in curcumin-treated rats compared to the MP- and saline-treated groups. Furthermore, curcumin significantly improved locomotor function. Curcumin treatment preserves neuronal viability against inflammation, oxidative stress, and apoptosis associated with ischemia-reperfusion injury.

Delayed injection of polypyrrole doped with iodine particle suspension after spinal cord injury in rats improves functional recovery and decreased tissue damage evaluated by 3.0 Tesla in vivo magnetic resonance imaging

Background ContextTraumatic spinal cord injury (SCI) causes irreversible damage with loss of motor, sensory, and autonomic functions. Currently, there is not an effective treatment to restore the lost neurologic functions. PurposeInjection of polypyrrole-iodine(PPy-I) particle suspension is proposed as a therapeutic strategy. Study DesignThis is an in vivo animal study. MethodsThis study evaluates the use of such particles in rats after SCI by examining spared nervous tissue and the Basso, Beattie, and Bresnahan (BBB) scale to evaluate the functional outcome. Diffusive magnetic resonance imaging (MRI) was employed to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) as non-invasive biomarkers of damage after SCI. ResultsFractional anisotropy decreased, whereas ADC increased in all groups after the lesion. There were significant differences in FA when compared with the SCI-PPy-I group versus the SCI group (p<.05). Significant positive correlations between BBB and FA (r2=0.449, p<.05) and between FA and preserved tissue (r2=0.395, p<.05) were observed, whereas significant negative associations between BBB and ADC (r2=0.367, p<.05) and between ADC and preserved tissue (r2=0.421, p<.05) were observed. ConclusionsThe results suggested that PPy-I is neuroprotective as it decreased the amount of damaged tissue while improving the motor function. Non-invasive MRI proved to be useful in the characterization of SCI and recovery.

Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis.

OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the spinal cord.

Effects of ganglioside G(M1) and erythropoietin on spinal cord lesions in rats: functional and histological evaluations

OBJECTIVE:To evaluate the functional and histological effects of ganglioside G(M1) and erythropoietin after experimental spinal cord contusion injury.METHODS:Fifty male Wistar rats underwent experimental spinal cord lesioning using an NYU-Impactor device and were randomly divided into the following groups, which received treatment intraperitoneally. The G(M1) group received ganglioside G(M1) (30 mg/kg); the erythropoietin group received erythropoietin (1000 IU/kg); the combined group received both drugs; and the saline group received saline (0.9%) as a control. A fifth group was the laminectomy group, in which the animals were subjected to laminectomy alone, without spinal lesioning or treatment. The animals were evaluated according to the Basso, Beattie and Bresnahan (BBB) scale, motor evoked potential recordings and, after euthanasia, histological analysis of spinal cord tissue.RESULTS:The erythropoietin group had higher BBB scores than the G(M1) group. The combined group had the highest BBB scores, and the saline group had the lowest BBB scores. No significant difference in latency was observed between the three groups that underwent spinal cord lesioning and intervention. However, the combined group showed a significantly higher signal amplitude than the other treatment groups or the saline group (p<0.01). Histological tissue analysis showed no significant difference between the groups. Axonal index was significantly enhanced in the combined group than any other intervention (p<0.01).CONCLUSION:G(M1) and erythropoietin exert therapeutic effects on axonal regeneration and electrophysiological and motor functions in rats subjected to experimental spinal cord lesioning and administering these two substances in combination potentiates their effects.

IKVAV-linked cell membrane-spanning peptide treatment induces neuronal reactivation following spinal cord injury.

Spinal cord regeneration following treatment with a novel membrane-spanning peptide (MSP) expressing the isoleucine-lysine-valine-alanine-valine (IKVAV) epitope was assessed in Balb-c mice. After hemilaminectomy and compression injury, mice were treated with IKVAV, IKVAV-MSP, peptide or vehicle control. Functional improvement was assessed using modified Basso, Beattie, and Bresnahan Scale (mBBB) and spinal cord segments were studied histologically 28 days after injury. IKVAV-MSP group scores increased significantly compared with control groups after 4 weeks of observation (p < 0.05). The number of protoplasmic astrocytes, neurons and muscle bundle size in the IKVAV-MSP mice were significantly increased (p < 0.001; p < 0.05 and p < 0.007; respectively). This study demonstrates that it is possible to promote functional recovery after SCI using bioactive IKVAV presenting cell membrane-spanning peptides.

Hydroalcoholic extract of red propolis promotes functional recovery and axon repair after sciatic nerve injury in rats

Context: Peripheral axon injury and degeneration are often mediated by oxidative stress and inflammation. The hydroalcoholic extract of the red propolis (HERP) has attracted great attention because of its antioxidant and anti-inflammatory activities. Objective: The objective of this work is to study the effect of HERP on nerve repair and functional recovery after sciatic nerve injury (SNI) in rats. Materials and methods: The chemical markers in HERP were identified using high-resolution mass spectroscopy. After axonotmesis of sciatic nerve, ibuprofen (IBP) and HERP treatments were orally administered for 28 d. Behavioural tests were performed weekly after SNI. The myelinated axon number was counted using morphometric analysis. Results: The compounds found in HERP were pinocembrin, formononetin, vestitol, and biochanin A. The animals that underwent SNI showed a significant decrease in motor function based on the Basso, Beattie and Bresnahan scale and sciatic functional index compared with sham animals until 7 d after the surgery (p < 0.05). After 14 and 21 d, the SNI groups treated with either HERP or IBP showed significant improvement (p < 0.01), and the SNI group treated with HERP 10 mg/kg showed accelerated motor recovery compared with the other groups (p < 0.01). SNI caused also a reduction in the myelinated axon counts, and treatment with HERP 10 mg/kg induced a significant increase in the number of myelinated fibres compared with all other groups. Conclusion: HERP promoted regenerative responses and accelerated functional recovery after sciatic nerve crush. Thus, it can be considered to be a new strategy or complementary therapy for treating nerve injuries.

Effects of estrogen on functional and neurological recovery after spinal cord injury: An experimental study with rats

OBJECTIVES:To evaluate the functional and histological effects of estrogen as a neuroprotective agent after a standard experimentally induced spinal cord lesion.METHODS:In this experimental study, 20 male Wistar rats were divided into two groups: one group with rats undergoing spinal cord injury (SCI) at T10 and receiving estrogen therapy with 17-beta estradiol (4mg/kg) immediately following the injury and after the placement of skin sutures and a control group with rats only subjected to SCI. A moderate standard experimentally induced SCI was produced using a computerized device that dropped a weight on the rat's spine from a height of 12.5 mm. Functional recovery was verified with the Basso, Beattie and Bresnahan scale on the 2nd, 7th, 14th, 21st, 28th, 35th and 42nd days after injury and by quantifying the motor-evoked potential on the 42nd day after injury. Histopathological evaluation of the SCI area was performed after euthanasia on the 42nd day.RESULTS:The experimental group showed a significantly greater functional improvement from the 28th to the 42nd day of observation compared to the control group. The experimental group showed statistically significant improvements in the motor-evoked potential compared with the control group. The results of pathological histomorphometry evaluations showed a better neurological recovery in the experimental group, with respect to the proportion and diameter of the quantified nerve fibers.CONCLUSIONS:Estrogen administration provided benefits in neurological and functional motor recovery in rats with SCI beginning at the 28th day after injury.

A computerized system for the application of Basso, Beattie and Bresnahan scale in Wistar rats.

OBJECTIVES: To develop and test a computer program to assist researchers in assigning scores in the application of the Basso, Beattie and Bresnahan (BBB) scale and to compare these scores when doing so in free, targeted and automated computer-assisted modes. METHOD: To test the program, the participants used the Impactor methodology recommended by the New York University (USA), in which 12 Wistar rats submitted to spinal cord injury were filmed on the 28th day after the injury. Eight researchers from the Laboratory of Medical Investigation, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil took part in the study. The two heads of the laboratory, with 15 years of experience in the application of the scale, were considered the gold standard. RESULTS: The results of the scale application were not significantly different in relation to the gold standard, considering the mean of the evaluators in each method: free, targeted and automated form (with the help of the computer). CONCLUSIONS: The application of the BBB scale in the automated mode, using the computer program, did not present any difference in relation to the gold standard for all the evaluators. Level of Evidence II, Diagnostic Studies.

Comparative Study on the Effects of Ceftriaxone and Monocytes on Recovery after Spinal Cord Injury in Rat.

Comparison between the efficacy of ceftriaxone and monocytes on improvement of neuron protection and functional recovery after spinal cord injury (SCI) in rat. Rats were randomly divided into three groups of ten. Spinal cord injury was performed on rats under general anesthesia using the weight dropping method. Ceftriaxone was injected intraperitoneally 200 mg/kg/day for seven days after SCI. Monocytes were injected 2 × 105 cells 4 days after SCI. Hind limb motor function was assessed using the Basso, Beattie and Bresnahan (BBB) scale. Corticospinal tract (CST) axons were traced by injection of biotin dextran amine (BDA) into the sensorimotor cortex. There were statistically significant differences in BBB scores in ceftriaxone in comparison to both monocytes receiving and control groups. On the other hand there were statistically significant differences in axon counting in both ceftriaxone and monocytes receiving groups in comparison to control group. Our findings suggest that ceftriaxone improves functional recovery more effective than monocytes in rats after SCI. These results are from an experimental model and validation is required for further investigation.

Lewis, Fischer 344, and sprague-dawley rats display differences in lipid peroxidation, motor recovery, and rubrospinal tract preservation after spinal cord injury.

The rat is the most common animal model for the preclinical validation of neuroprotective therapies in spinal cord injury (SCI). Lipid peroxidation (LP) is a hallmark of the damage triggered after SCI. Free radicals react with fatty acids causing cellular and membrane disruption. LP accounts for a considerable amount of neuronal cell death after SCI. To better understand the implications of inbred and outbred rat strain selection on preclinical SCI research, we evaluated LP after laminectomy sham surgery and a severe contusion of the T9 spinal cord in female Sprague-Dawley (SPD), Lewis (LEW), and Fischer 344 (F344) rats. Further analysis included locomotor recovery using the Basso, Beattie, and Bresnahan (BBB) scale and retrograde rubrospinal tract tracing. LEW had the highest levels of LP products 72 h after sham surgery and SCI, significantly different from both F344 and SPD. SPD rats had the fastest functional recovery and highest BBB scores; these were not significantly different to F344. However, LEW rats achieved the lowest BBB scores throughout the 2-month follow-up, yielding significant differences when compared to SPD and F344. To see if the improvement in locomotion was secondary to an increase in axon survival, we evaluated rubrospinal neurons (RSNs) via retrograde labeling of the rubrospinal tract and quantified cells at the red nuclei. The highest numbers of RSNs were observed in SPD rats then F344; the lowest counts were seen in LEW rats. The BBB scores significantly correlated with the amount of positively stained RSN in the red nuclei. It is critical to identify interstrain variations as a potential confound in preclinical research. Multi-strain validation of neuroprotective therapies may increase chances of successful translation.

Motor Outcome and Histological Findings in a Clipping Model of Spinal Cord Injury: Comparison between Posterior and Lateral Clip Placement

Introduction Different types of spinal cord injury models in rats were described in the literature, including spinal cord clip compression. This type of procedure can be performed by placing the clip in two directions in relation to the spinal cord: lateral or posterior. Studies published in the literature usually do not describe the direction of the clip placement. It is assumed that the severity of neurological symptoms and the histological lesion are different from each other in these two models. The objective is to evaluate the locomotor and the histological impact on the spinal cord comparing lateral and posterior clip placement. Materials and Methods This study is a randomized experimental trial. A total of 20 female Wistar rats, ranging from 250 to 300 g, aged 12 to 14 weeks, were randomized in two groups by the direction of clip placement: lateral group ( n = 10) and posterior group ( n = 10). After exposing the thoracic segment of spine (T8–T10), a laminectomy was performed at the T9 level under microscope view. The spinal cord injury was made using a 5 mm long aneurismal clip with a closing pressure of 50 g. Locomotor behavior was evaluated by the Basso, Beattie, and Bresnahan scale at the 1st, 7th, 14th, 21st, and 28th day after surgery and the histological analysis of the injury area by computer software. Results The histological evaluation showed a greater lesion area in the lateral group, mean 2.3 ± 2 mm2, when compared with the posterior group, mean 4.8 ± 1 mm2 ( p = 0.03). There was no overall difference between lateral and posterior locomotor scores from day 1 to 28 ( p = 0.361). Conclusion The lesion area observed in the spinal cord histology after the lateral placement of a clip was significantly greater than in the posterior direction of the clip. There was no overall motor performance difference between lateral and posterior BBB scores.

Functional Recovery and in Vivo Cell Tracking after Human Adipose Tissue-Derived Stem Cells Therapy for Experimental Spinal Cord Injury

Introduction The use of human adipose tissue-derived stem cells (hADSC) as therapy in spinal cord injury (SCI) is a promising approach for the recovery of motor function of injured patients. This study aims to evaluate the effects of hADSC, applied to the cauda equina in an animal model of blunt spinal trauma, on their motor function. A secondary aim is to analyze cell migration toward the injury site. Method All samples were collected after an informed consent had been obtained in accordance with guidelines for research involving human subjects, and with the approval of the ethics committee (approval number 769). A total of 40 Wistar rats were anesthetized, injured at Th10 using the NYU impactor device and randomly divided into four groups: Group A, animals were submitted to one culture medium injection immediately after injury; group B, animals were submitted to two culture medium injections, immediately after and 7 days postlesion; group C, animals were submitted to one cell injection (1 × 106 cells) immediately after injury and group D, animals were submitted to two cell injections, immediately after and 7 days postlesion. Standard animal care, according to the university's protocol was maintained for 40 days with motor analysis every 72 hours using the Basso, Beattie, and Bresnahan (BBB) scale. Some animals were transplanted with luc gene-transduced cells to evaluate cell migration, which was assessed by in vivo bioluminescence images of animals in groups C and D (IVIS Lumina II). Results A statistically significant recovery of motor function was observed in animals transplanted with hADSC compared with the control group ( p = 0.007 for one injection protocol, p = 0.005 for the two injection protocol). No differences were observed between one and two injection protocols ( p = 0.13). Bioluminescence analysis revealed cell migration to the injury site after injection. Conclusion hADSC injected at the cauda equina migrate toward the injury site and promote significant motor recovery.

Tissue-engineered regeneration of completely transected spinal cord using induced neural stem cells and gelatin-electrospun poly (lactide-co-glycolide)/polyethylene glycol scaffolds.

Tissue engineering has brought new possibilities for the treatment of spinal cord injury. Two important components for tissue engineering of the spinal cord include a suitable cell source and scaffold. In our study, we investigated induced mouse embryonic fibroblasts (MEFs) directly reprogrammed into neural stem cells (iNSCs), as a cell source. Three-dimensional (3D) electrospun poly (lactide-co-glycolide)/polyethylene glycol (PLGA-PEG) nanofiber scaffolds were used for iNSCs adhesion and growth. Cell growth, survival and proliferation on the scaffolds were investigated. Scanning electron microcopy (SEM) and nuclei staining were used to assess cell growth on the scaffolds. Scaffolds with iNSCs were then transplanted into transected rat spinal cords. Two or 8 weeks following transplantation, immunofluorescence was performed to determine iNSC survival and differentiation within the scaffolds. Functional recovery was assessed using the Basso, Beattie, Bresnahan (BBB) Scale. Results indicated that iNSCs showed similar morphological features with wild-type neural stem cells (wt-NSCs), and expressed a variety of neural stem cell marker genes. Furthermore, iNSCs were shown to survive, with the ability to self-renew and undergo neural differentiation into neurons and glial cells within the 3D scaffolds in vivo. The iNSC-seeded scaffolds restored the continuity of the spinal cord and reduced cavity formation. Additionally, iNSC-seeded scaffolds contributed to functional recovery of the spinal cord. Therefore, PLGA-PEG scaffolds seeded with iNSCs may serve as promising supporting transplants for repairing spinal cord injury (SCI).

Lentivirus-mediated inhibition of tumour necrosis factor-α improves motor function associated with PRDX6 in spinal cord contusion rats.

The recovery of motor function in rats is inhibited following contusion spinal cord injury (cSCI). However, the mechanism of tumour necrosis factor α (TNF-α) in motor function after cSCI associated with peroxiredoxin 6 (PRDX6) remains unknown. We randomly divided rats into four groups: sham, cSCI, vector and lentivirus mediating TNF-α RNA interference (TNF-α-RNAi-LV) group. The Basso, Beattie, Bresnahan (BBB) scale was used to evaluate motor function. Real-time quantitative PCR (qRT-PCR) and western blotting were used to detect the expression of TNF-α and PRDX6, which were located in neurons using immunohistochemistry (IHC) and immunofluorescence. Subsequently, lentiviral-mediated TNF-α was used to determine the role of TNF-αand the relationship of PRDX6 and TNF-α in cSCI. After cSCI, the motor capability of hind limbs disappeared and was followed by recovery of function. IHC analysis indicated that TNF-α and PRDX6 were primarily located in spinal cord neurons. TNF-α interference significantly improved neural behaviour and increased expression of PRDX6. Our study suggests that inhibition of TNF-α can promote the recovery of motor function. The underlying mechanism of TNF-α-promoted motor function may be connected with the up-regulation of PRDX6. This provides a new strategy or target for the clinical treatment of SCI in future.

Improvements in neuroelectrophysiological and rear limb functions in rats with spinal cord injury after Schwann cell transplantation in combination with a C5a receptor antagonist.

We measured the effect of Schwann cell transplantation and complement factor 5a (C5a) receptor antagonist on nerve function recovery in rats with spinal cord injury. Experimental spinal cord injury was induced in eighty Wistar rats and these were randomly divided into four treatment groups: culture medium and saline injection (control group), Schwann cell injection (cell transplantation group), C5a receptor antagonist injection (C5a receptor antagonist group), and both Schwann cell and C5a receptor antagonist injections (combination group). Rear limb functional recovery was assessed 1, 2, 4, 6, and 8 weeks after the spinal cord injury with the tilt table test and the Basso, Beattie, Bresnahan scale. Sex-determining region Y (SRY) gene expression was measured at week 4 and horseradish peroxidase (HRP) labeling was used at week 8 to further assess the recovery of neuroelectrophysiological functions. The rear limb functional assessment showed that the combination group had better outcomes than the cell transplantation and C5a receptor antagonist groups. All treatment groups had better outcomes than control. Only the cell transplantation and combination groups showed SRY expression. The number of HRP-positive nerve fibers in the different groups ranked as follows: combination group > cell transplantation and C5a receptor antagonist > control. The refractory period and amplitude of the induced potential in the combination group were significantly greater than in the other three groups. These results suggest that the combination of Schwann cell transplantation and the C5a receptor antagonist enhances the regeneration of injured synapses and improves limb function and electrophysiology.

Panax notoginseng saponins improve recovery after spinal cord transection by upregulating neurotrophic factors.

Saponins extracted from Panax notoginseng are neuroprotective, but the mechanisms underlying this effect remain unclear. In the present study, we established a rat model of thoracic (T10) spinal cord transection, and injected Panax notoginseng saponins (100 mg/kg) or saline 30 minutes after injury. Locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) scale from 1 to 30 days after injury, and immunohistochemistry was carried out in the ventral horn of the spinal cord at 1 and 7 days to determine expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Our results show that at 7–30 days post injury, the BBB score was higher in rats treated with Panax notoginseng saponins than in those that received saline. Furthermore, at 7 days, more NGF- and BDNF-immunoreactive neurons were observed in the ventral horn of the spinal cord of rats that had received Panax notoginseng saponins than in those that received saline. These results indicate that Panax notoginseng saponins caused an upregulation of NGF and BDNF in rats with spinal cord transection, and improved hindlimb motor function.

Motor and histological findings in a model of sci: comparison between posterior and lateral clips

Objective: To evaluate the locomotor and histological impact on the spinal cord comparing lateral and posterior clip placement. Method: Randomized experimental trial. Twenty female Wistar rats, weighing between 250 and 300 grams and aged 12-14 weeks were randomized in two groups according to the placement of the clip: lateral group (N=10) and posterior group (N=10). After exposing the thoracic segment of the spine (T8-T10), a laminectomy was performed at the T9 level under microscopic view. The spinal cord injury was made using a 5 mm long aneurysm clip with a closing pressure of 50 grams. Locomotor behavior was evaluated by the Basso, Beattie and Bresnahan scale in days 1, 7, 14, 21, and 28 after surgery. The area of injury was assessed by histological analysis and measured by a software. Results: The histological evaluation showed a larger mean area of 4.8&amp;#177;1mm&amp;#178; of lesion (P=0.03) in the lateral group when compared with the posterior group mean area of 2.3&amp;#177;2mm&amp;#178;. There was no significant difference between lateral and posterior groups with respect to locomotor scores from day 1 to 28 (P=0.361). Conclusion: The lesion area observed in the spinal cord histology after lateral placement of a clip was significantly bigger than in the posterior placement. The motor evaluation showed similar BBB scores regardless of the type of clamping method.

Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury

Extracorporeal shock wave therapy (ESWT) is widely used for the clinical treatment of various human diseases. Recent studies have demonstrated that low-energy ESWT upregulates the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis and functional recovery in myocardial infarction and peripheral artery disease. Many previous reports suggested that VEGF produces a neuroprotective effect to reduce secondary neural tissue damage after spinal cord injury (SCI). The purpose of the present study was to investigate whether low-energy ESWT promotes VEGF expression and neuroprotection and improves locomotor recovery after SCI. Sixty adult female Sprague-Dawley rats were randomly divided into 4 groups: sham group (laminectomy only), sham-SW group (low-energy ESWT applied after laminectomy), SCI group (SCI only), and SCI-SW group (low-energy ESWT applied after SCI). Thoracic spinal cord contusion injury was inflicted using an impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) Scale (open field locomotor score) at different time points over 42 days after SCI. Hematoxylin and eosin staining was performed to assess neural tissue damage in the spinal cord. Neuronal loss was investigated by immunostaining for NeuN. The mRNA expressions of VEGF and its receptor, Flt-1, in the spinal cord were assessed using real-time polymerase chain reaction. Immunostaining for VEGF was performed to evaluate VEGF protein expression in the spinal cord. In both the sham and sham-SW groups, no animals showed locomotor impairment on BBB scoring. Histological analysis of H & E and NeuN stainings in the sham-SW group confirmed that no neural tissue damage was induced by the low-energy ESWT. Importantly, animals in the SCI-SW group demonstrated significantly better locomotor improvement than those in the SCI group at 7, 35, and 42 days after injury (p < 0.05). The number of NeuN-positive cells in the SCI-SW group was significantly higher than that in the SCI group at 42 days after injury (p < 0.05). In addition, mRNA expressions of VEGF and Flt-1 were significantly increased in the SCI-SW group compared with the SCI group at 7 days after injury (p < 0.05). The expression of VEGF protein in the SCI-SW group was significantly higher than that in the SCI group at 7 days (p < 0.01). The present study showed that low-energy ESWT significantly increased expressions of VEGF and Flt-1 in the spinal cord without any detrimental effect. Furthermore, it significantly reduced neuronal loss in damaged neural tissue and improved locomotor function after SCI. These results suggested that low-energy ESWT enhances the neuroprotective effect of VEGF in reducing secondary injury and leads to better locomotor recovery following SCI. This study provides the first evidence that low-energy ESWT can be a safe and promising therapeutic strategy for SCI.