Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functiona...Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting Rho A expression. We established a rat model of acute spinal cord injury using a modification of Allen's method. The rats were given electroacupuncture treatment at Dazhui(Du14), Mingmen(Du4), Sanyinjiao(SP6), Huantiao(GB30), Zusanli(ST36) and Kunlun(BL60) acupoints with a sparsedense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan(BBB) locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and Rho A and Nogo-A m RNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases Rho A and Nogo-A m RNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery.展开更多
Objective: To investigate the effect and significance of electroacupuncture (EA) on neuronal apoptosis and hindlimb motor and bladder functional improvement in rats with acute spinal cord injury (SCI). Methods: Sixty ...Objective: To investigate the effect and significance of electroacupuncture (EA) on neuronal apoptosis and hindlimb motor and bladder functional improvement in rats with acute spinal cord injury (SCI). Methods: Sixty healthy Sprague Dawley rats were randomly assigned to sham, model, EA, and EA control groups (n = 15 each). EA group rats received EA treatment at Zhibian and Shuidao acupoints seven times daily, whereas EA control group rats received EA at two points, 0.5 cm away from Zhibian and Shuidao, respectively. Histomorphological changes in spinal cord tissue were examined using hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL assay. Bcl-2, Bax, and Bad protein levels were detected using immunohistochemistry. Additionally, hindlimb motor function, residual urine volume and maximum bladder capacity were measured. Results: HE staining revealed a morphologically and structurally intact spinal cord in the EA group, and the tissue contained scattered blood cells without edema. In the EA control group, there were small morphological defects in the spinal cord, and the tissue contained fewer blood cells with local edema. Compared with the EA control and model groups, Bax and Bad levels were significantly decreased in the EA group and Bcl-2 expression was increased (P < 0.05). After SCI, hindlimb function scores, residual urine volume, and maximum bladder capacity in rats of the EA group significantly differed from those of the EA control group (P < 0.05). Conclusion: EA may induce SCI-induced improvements in hindlimb motor and bladder functions by affecting neuronal apoptosis and relevant gene expression changes.展开更多
Electroacupuncture at Dazhui(GV14) and Mingmen(GV4) on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this stu...Electroacupuncture at Dazhui(GV14) and Mingmen(GV4) on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this study, we established rat models of spinal cord injury using a modified Allen's weight-drop method. Ninety-nine male Sprague-Dawley rats were randomly divided into three equal groups: sham(only laminectomy), SCI(induction of spinal cord injury at T10), and EA(induction of spinal cord injury at T10 and electroacupuncture intervention at GV14 and GV4 for 20 minutes once a day). Rats in the SCI and EA groups were further randomly divided into the following subgroups: 1-day(n = 11), 7-day(n = 11), and 14-day(n = 11). At 1, 7, and 14 days after electroacupuncture treatment, the Basso, Beattie and Bresnahan locomotor rating scale showed obvious improvement in rat hind limb locomotor function, hematoxylin-eosin staining showed that the histological change of injured spinal cord tissue was obviously alleviated, and immunohistochemistry and western blot analysis showed that Wnt1, Wnt3 a, β-catenin immunoreactivity and protein expression in the injured spinal cord tissue were greatly increased compared with the sham and SCI groups. These findings suggest that electroacupuncture at GV14 and GV4 upregulates Wnt1, Wnt3 a, and β-catenin expression in the Wnt/β-catenin signaling pathway, exhibiting neuroprotective effects against spinal cord injury.展开更多
Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase(ROCK) signaling pathway regulates the actin cytoskeleton by controlling...Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase(ROCK) signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan(GV3), Dazhui(GV14), Zusanli(ST36) and Ciliao(BL32) and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the m RNA and protein expression of Rho-A and Rho-associated kinase Ⅱ(ROCKⅡ) of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKⅡ. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKⅡ. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of Rho A and ROCKⅡ. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.展开更多
This study established the following groups of rats: a normal group, a sham surgery group, a spinal cord injury model group, a low-frequency electroacupuncture group, a high-frequency electroacupuncture group and a s...This study established the following groups of rats: a normal group, a sham surgery group, a spinal cord injury model group, a low-frequency electroacupuncture group, a high-frequency electroacupuncture group and a semen coicis group. In all but the normal and sham surgery groups the left half of Tlo was transected. Four hours after model induction, 5-Hz and 100-Hz electroacupuncture were used to stimulate the acupoints I-luantiao (GB 30), Zusan/i (ST 36), Zhiyan9 (DU 9) and Xuanshu (DU 5), or crude extract from semen coicis was intraperitoneally injected, for 8 consecutive weeks. The results indicated that electroacupuncture stimulation and intraperitoneal injection of semen coicis improved the morphology of spinal cord tissue, promoted the recovery of motion-evoked potentials, suppressed glial fibrillary acidic protein expression, and ameliorated motor function in rats with hemisection spinal cord injury. The effects of high-frequency (100 Hz) electroacupuncture ancl semen coicis were significant.展开更多
Objective: To observe the effect of electroacupuncture(EA) combined with oriented conductive bioprotein hydrogel(OCBH) on the recovery of nerve function in rats with complete spinal cord injury(SCI)and to explore its ...Objective: To observe the effect of electroacupuncture(EA) combined with oriented conductive bioprotein hydrogel(OCBH) on the recovery of nerve function in rats with complete spinal cord injury(SCI)and to explore its effect and mechanism on the formation and changes of glial scars.Methods: A total of 72 female Sprague-Dawley rats were randomly divided into groups according to the treatment received. A rat model of complete SCI was constructed using a spinal cord transection.Behavioral assessments, hematoxylin-eosin(H&E) staining, immunofluorescence staining, and Western blotting were performed at a fixed period after the operation.Results: The material group and the material + EA group obtained better results in the behavioral assessments(all P <.05) and the H&E staining. In the immunofluorescence staining and Western blotting,the GFAP protein was expressed more and denser in the material group and the material + EA group than in the model group, and the density of the GFAP expression in the material + EA group was lower at week 12 than in the material group(all P <.05). The expression of complement C3 in the model, material,and material + EA groups decreased in turn. Some inflammatory factors and the NF-κB signaling pathway showed similar results in the Western blotting(all P <.05). The expression of the GDNF protein in the material + EA group was significantly higher than that in the model group and the material group(both P <.01).Conclusion: EA combined with OCBH can promote the recovery of motor functions after SCI by facilitating the formation of glial scars in the early stage, preventing the further spread of an inflammatory response that would affect the activation of A1/A2 astrocytes and change the morphology of glial scars at the spinal cord-material interface in its late stage.展开更多
Objective:To observe the effect of electroacupuncture at Jiaji (EX-B2) points on the expression of microRNA-21 and neuronal apoptosis in rats with acute spinal cord injury. Methods:SD rats were randomly divided into s...Objective:To observe the effect of electroacupuncture at Jiaji (EX-B2) points on the expression of microRNA-21 and neuronal apoptosis in rats with acute spinal cord injury. Methods:SD rats were randomly divided into sham-operated group, model group, electro-acupuncture group and methylprednisolone group. The model of acute spinal cord injury was reproduced by modified Allen's method. Each group was given corresponding intervention treatment 2 hours after modeling. The electroacupuncture group was treated with electro-acupuncture at Jiaji (EX-B2) points in T8 to T12, the methylprednisolone group was given intraperitoneal injection of 30 mg/kg methylprednisolone sodium succinate, and the sham operation group and model group were not treated. After treatment, BBB scores were observed to evaluate the motor function of posterior limb in each group, and the injured spinal cord tissues were taken. The pathological changes of spinal cord neuropathy were observed by Nissl staining. The expression of microRNA-21 was detected by RT-qPCR, and the expression of apoptotic proteins (Bax, Bcl-2 and cleaved-Caspase-3) was detected by Western-Blot. Result:Compared with sham operation group, BBB, neuron survival rate and expression of microRNA-21 were significantly lower, apoptotic rate of neurons was significantly higher, expression of Bax, Bcl-2, cleaved Caspase-3 protein and Bax/Bcl-2 ratio were significantly increased in model group (P< 0.05). Electroacupuncture could significantly increase BBB score, neuron survival rate and expression of microRNA-21, reduce apoptotic rate of neurons and the ratio of Bax/Bcl-2, and inhibit the expression of Bax, Bcl-2 and cleaved Caspase-3 protein in tissues, which were significantly different from those of model group (P< 0.05). Conclusions: Electroacupuncture at Jiaji (EX-B2) points can significantly promote the recovery of neurological function in rats after ASCI, and its mechanism may be closely related to the up-regulation of the expression of microRNA-21 in tissues and the inhibition of the activation of Bax/Bcl-2/cleaved Caspase-3 signaling pathway.展开更多
Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury...Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli(ST36),Xuanzhong(GB39),Futu(ST32)and Sanyinjiao(SP6)were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase(ACh E)activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor(GDNF)m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury.展开更多
The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal c...The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Allen's method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also well recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additionally, anterior tibial muscle fibers slowly, but progressively, atrophied. Immu- nohistochemical staining showed that the absorbance values of calcitonin gene related peptide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic fi- broblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related peptide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through gene related peptide and acetylcholinesterase cord. attenuating the decreased expression of calcitonin n anterior horn motor neurons of the injured spinal展开更多
A contusive model of spinal cord injury at spinal segment T8-9 was established in rats. Huantiao (GB30) and Huatuojiaji (Ex-B05) were punctured with needles, and endogenous neural stem cells were labeled with 5-br...A contusive model of spinal cord injury at spinal segment T8-9 was established in rats. Huantiao (GB30) and Huatuojiaji (Ex-B05) were punctured with needles, and endogenous neural stem cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) and NG2. Double immunofluorescence staining showed that electroacupuncture markedly increased the numbers of BrdU+/NG2+cells at spinal cord tissue 15 mm away from the injury center in the rostral and caudal directions. The results suggest that electroacupuncture promotes the proliferation of endogenous neural stem cells and oligodendrocytes in rats with spinal cord injury.展开更多
Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatme...Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury.Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord.In this study,Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury.The rat models were established by inserting a balloon catheter into the atlanto-occipital space.The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression.Electroacupuncture was conducted at the acupoints Dazhui(GV14) and Baihui(GV 20)(2 Hz,15 minutes) once a day for 14 consecutive days.Compared with decompression alone,hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture.However,the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours.Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone.These findings indicate that compared with decompression alone,Governor Vessel electroacupuncture combined with delayed decompression(48 hours) is more effective in the treatment of upper cervical spinal cord injury.Governor Vessel electroacupuncture combined with early decompression(12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury.Nevertheless,further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone.展开更多
OBJECTIVE: To formulate an evidence-based treatment for one patient with acute spinal cord injury and summarize evidence for evaluating acute spinal cord injury treatment. METHODS: Studies related to the treatment f...OBJECTIVE: To formulate an evidence-based treatment for one patient with acute spinal cord injury and summarize evidence for evaluating acute spinal cord injury treatment. METHODS: Studies related to the treatment for acute spinal cord injury were identified via a search of National Guideline Clearinghouse (NGC, 2000 11), the Cochrane Library (Issue 1,2011), TRIP Database (2000 11), and PubMed (1966-2011). Treatment strategies were formulated according to three basic principles: best evidence, doctor's professional experience, and wishes of the patient. RESULTS: A total of 34 articles were selected, including 1 NGC guideline, 22 systematic reviews, and 11 randomized controlled trials. Based on our review, we arrived at the following recommendations: no clinical evidence exists definitively to recommend the use of any of neuroprotective pharmaceuticals; surgery should be undertaken early; mechanical compression devices and low-molecular weight heparin should be employed to prevent thrombosis; respiratory muscle training is beneficial for pulmonary function and quality of life; and functional electrical stimulation and acupuncture can promote functional recovery. The patient accordingly underwent surgery 6 hours after trauma without receiving any neuroprotective pharmaceuticals; low-molecular weight heparin and intermittent pneumatic compression were applied to prevent thrombosis. He also underwent respiratory muscle training daily for 8 weeks and received functional electrical stimulation for 15 minutes and acupuncture for 30 minutes every day. After follow-up for 3 months, the above therapeutic regimen was confirmed efficacious for acute spinal cord injury. CONCLUSION: Evidence-based medicine provides an individualized treatment protocol for acute spinal cord injury, which can significantly improve the therapeutic effect and prognosis.展开更多
Effect of acupuncture on free radicals after spinal cord injury was observed in rats with experimental spinal cord injury (SCI). Results indicated that within 24 hours after SCI malondialdehyde (MDA) increased pro... Effect of acupuncture on free radicals after spinal cord injury was observed in rats with experimental spinal cord injury (SCI). Results indicated that within 24 hours after SCI malondialdehyde (MDA) increased progressively, 2 hours after SCI it reached the peak; and the superoxide dismutase (SOD) activity decreased significantly at the same hours, the decrease being the most marked 2-6 hours after SCI. The MDA content in the acupuncture group was significantly lower (P<0.05) and the SOD activity higher (P<0.01) than that of the control group respectively. It is suggested that acupuncture inhibits production of MDA and increases the SOD activity.……展开更多
Background:The inhibitory microenvironment around spinal cord injury(SCI)severely restricted functional repair after injury.Mitophagy was one of the important measures to maintain cellular homeostasis and ensure the h...Background:The inhibitory microenvironment around spinal cord injury(SCI)severely restricted functional repair after injury.Mitophagy was one of the important measures to maintain cellular homeostasis and ensure the harmonious nerve cell microenvironment.Hypoxia-inducible factor1α(HIF1-α)can mediate mitochondrial autophagy in neurodegenerative diseases,but the mechanisms are complex and diverse,which need to be further elucidated.Electroacupuncture plays a significant role in improving the neural microenvironment after spinal cord injury,promote long-term neurological function recovery in SCI patients,but whether electroacupuncture can participate in HIF1-α mediated mitophagy remains unknown.Objective:Investigated the effects of HIF1-α on mitochondrial autophagy in rats with spinal cord contusion and the potential mechanism of electroacupuncture.Methods:Following the successful construction of an SCI model of Sprague-Dawley rat utilizing a modified Allen method,electroacupuncture intervention was performed at T9 and T11 Jiaji acupoint(EX-B2),with further molecular biology and morphology examined by perfusion.To observe the effect of HIF1-α on local damage repair,the stereotypic injection of Hif1a knockdown virus was performed,and the changes of mitophagy in damaged local area was detected employing Western blotting,real-time fluorescence quantitative PCR,immunofluorescence,transmission electron microscopy and Nissl staining.Results:HIF1-α as well as its mitophagy receptor BNIP3 and NIX are upregulated after spinal cord injury.Elec-troacupuncture treatment or local inhibition of HIF1-α expression can reverse the early autophagy state after spinal cord injury,reduce cell apoptosis and injury area,promote neuronal survival.Conclusion:Electroacupuncture may serve as a promising strategy for spinal cord injury treatment,by alleviating HIF1-α mediated early mitochondrial autophagy.展开更多
The incidence of spinal cord injury(SCI) has been gradually increasing, and the treatment has troubled the medical field all the time. Primary and secondary injuries ultimately lead to nerve impulse conduction block. ...The incidence of spinal cord injury(SCI) has been gradually increasing, and the treatment has troubled the medical field all the time. Primary and secondary injuries ultimately lead to nerve impulse conduction block. Microglia and astrocytes excessively accumulate and proliferate to form the glial scar. At present, to reduce the effect of glial scar on nerve regeneration is a hot spot in the research on the treatment of SCI. According to the preliminary experiments, we would like to provide a new bionic spinal cord to reduce the negative effect of glial scar on nerve regeneration. In this hypothesis we designed a new scaffold that combine the common advantage of acellular scaffold of spinal cord and thermosensitive gel, which could continue to release exogenous basic fibroblast growth factor(BFGF) in the spinal lesion area on the basis of BFGF modified thermosensitive gel. Meanwhile, the porosity, pore size and material of the gray matter and white matter regions were distinguished by an isolation layer, so as to induce the directed differentiation of cells into the defect site and promote regeneration of spinal cord tissue.展开更多
Patients with potential spinal stenosis are susceptible to central cord syndrome induced by blunt trauma.Suitable animal models are helpful for studying the pathogenesis and treatment of such injuries.In this study,we...Patients with potential spinal stenosis are susceptible to central cord syndrome induced by blunt trauma.Suitable animal models are helpful for studying the pathogenesis and treatment of such injuries.In this study,we established a mouse model of acute blunt traumatic spinal cord injury by compressing the C6 spinal cord with 5 and 10 g/mm~2 compression weights to simulate cervical central cord syndrome.Behavioral testing confirmed that this model exhibited the characteristics of central cord syndrome because motor function in the front paws was impaired,whereas basic motor and sensory functions of the lower extremities were retained.Hematoxylin-eosin staining showed that the diseased region of the spinal cord in this mouse model was restricted to the gray matter of the central cord,whereas the white matter was rarely affected.Magnetic resonance imaging showed a hypointense signal in the lesion after mild and severe injury.In addition,immunofluorescence staining showed that the degree of nerve tract injury in the spinal cord white matter was mild,and that there was a chronic inflammation reaction.These findings suggest that this mouse model of central cord syndrome can be used as a model for preclinical research,and that gray matter is most vulnerable to injury in central cord syndrome,leading to impaired motor function.展开更多
基金supported by a grant from the Science and Technology Development Program of Jilin Province of China,No.2011084
文摘Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting Rho A expression. We established a rat model of acute spinal cord injury using a modification of Allen's method. The rats were given electroacupuncture treatment at Dazhui(Du14), Mingmen(Du4), Sanyinjiao(SP6), Huantiao(GB30), Zusanli(ST36) and Kunlun(BL60) acupoints with a sparsedense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan(BBB) locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and Rho A and Nogo-A m RNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases Rho A and Nogo-A m RNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery.
文摘Objective: To investigate the effect and significance of electroacupuncture (EA) on neuronal apoptosis and hindlimb motor and bladder functional improvement in rats with acute spinal cord injury (SCI). Methods: Sixty healthy Sprague Dawley rats were randomly assigned to sham, model, EA, and EA control groups (n = 15 each). EA group rats received EA treatment at Zhibian and Shuidao acupoints seven times daily, whereas EA control group rats received EA at two points, 0.5 cm away from Zhibian and Shuidao, respectively. Histomorphological changes in spinal cord tissue were examined using hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL assay. Bcl-2, Bax, and Bad protein levels were detected using immunohistochemistry. Additionally, hindlimb motor function, residual urine volume and maximum bladder capacity were measured. Results: HE staining revealed a morphologically and structurally intact spinal cord in the EA group, and the tissue contained scattered blood cells without edema. In the EA control group, there were small morphological defects in the spinal cord, and the tissue contained fewer blood cells with local edema. Compared with the EA control and model groups, Bax and Bad levels were significantly decreased in the EA group and Bcl-2 expression was increased (P < 0.05). After SCI, hindlimb function scores, residual urine volume, and maximum bladder capacity in rats of the EA group significantly differed from those of the EA control group (P < 0.05). Conclusion: EA may induce SCI-induced improvements in hindlimb motor and bladder functions by affecting neuronal apoptosis and relevant gene expression changes.
基金supported by the National Natural Science Foundation of China,No.81373728
文摘Electroacupuncture at Dazhui(GV14) and Mingmen(GV4) on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this study, we established rat models of spinal cord injury using a modified Allen's weight-drop method. Ninety-nine male Sprague-Dawley rats were randomly divided into three equal groups: sham(only laminectomy), SCI(induction of spinal cord injury at T10), and EA(induction of spinal cord injury at T10 and electroacupuncture intervention at GV14 and GV4 for 20 minutes once a day). Rats in the SCI and EA groups were further randomly divided into the following subgroups: 1-day(n = 11), 7-day(n = 11), and 14-day(n = 11). At 1, 7, and 14 days after electroacupuncture treatment, the Basso, Beattie and Bresnahan locomotor rating scale showed obvious improvement in rat hind limb locomotor function, hematoxylin-eosin staining showed that the histological change of injured spinal cord tissue was obviously alleviated, and immunohistochemistry and western blot analysis showed that Wnt1, Wnt3 a, β-catenin immunoreactivity and protein expression in the injured spinal cord tissue were greatly increased compared with the sham and SCI groups. These findings suggest that electroacupuncture at GV14 and GV4 upregulates Wnt1, Wnt3 a, and β-catenin expression in the Wnt/β-catenin signaling pathway, exhibiting neuroprotective effects against spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.81360562
文摘Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase(ROCK) signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan(GV3), Dazhui(GV14), Zusanli(ST36) and Ciliao(BL32) and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the m RNA and protein expression of Rho-A and Rho-associated kinase Ⅱ(ROCKⅡ) of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKⅡ. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKⅡ. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of Rho A and ROCKⅡ. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.
基金the High-funded Projects of Japan Science and Technology Ministry,No. 343the National Natural Science Foundation of China,No. 30772838
文摘This study established the following groups of rats: a normal group, a sham surgery group, a spinal cord injury model group, a low-frequency electroacupuncture group, a high-frequency electroacupuncture group and a semen coicis group. In all but the normal and sham surgery groups the left half of Tlo was transected. Four hours after model induction, 5-Hz and 100-Hz electroacupuncture were used to stimulate the acupoints I-luantiao (GB 30), Zusan/i (ST 36), Zhiyan9 (DU 9) and Xuanshu (DU 5), or crude extract from semen coicis was intraperitoneally injected, for 8 consecutive weeks. The results indicated that electroacupuncture stimulation and intraperitoneal injection of semen coicis improved the morphology of spinal cord tissue, promoted the recovery of motion-evoked potentials, suppressed glial fibrillary acidic protein expression, and ameliorated motor function in rats with hemisection spinal cord injury. The effects of high-frequency (100 Hz) electroacupuncture ancl semen coicis were significant.
基金financially supported by the National Natural Science Foundation of China (81973882 and 81804119)
文摘Objective: To observe the effect of electroacupuncture(EA) combined with oriented conductive bioprotein hydrogel(OCBH) on the recovery of nerve function in rats with complete spinal cord injury(SCI)and to explore its effect and mechanism on the formation and changes of glial scars.Methods: A total of 72 female Sprague-Dawley rats were randomly divided into groups according to the treatment received. A rat model of complete SCI was constructed using a spinal cord transection.Behavioral assessments, hematoxylin-eosin(H&E) staining, immunofluorescence staining, and Western blotting were performed at a fixed period after the operation.Results: The material group and the material + EA group obtained better results in the behavioral assessments(all P <.05) and the H&E staining. In the immunofluorescence staining and Western blotting,the GFAP protein was expressed more and denser in the material group and the material + EA group than in the model group, and the density of the GFAP expression in the material + EA group was lower at week 12 than in the material group(all P <.05). The expression of complement C3 in the model, material,and material + EA groups decreased in turn. Some inflammatory factors and the NF-κB signaling pathway showed similar results in the Western blotting(all P <.05). The expression of the GDNF protein in the material + EA group was significantly higher than that in the model group and the material group(both P <.01).Conclusion: EA combined with OCBH can promote the recovery of motor functions after SCI by facilitating the formation of glial scars in the early stage, preventing the further spread of an inflammatory response that would affect the activation of A1/A2 astrocytes and change the morphology of glial scars at the spinal cord-material interface in its late stage.
基金National Natural Science Foundation of China(81674077 S).
文摘Objective:To observe the effect of electroacupuncture at Jiaji (EX-B2) points on the expression of microRNA-21 and neuronal apoptosis in rats with acute spinal cord injury. Methods:SD rats were randomly divided into sham-operated group, model group, electro-acupuncture group and methylprednisolone group. The model of acute spinal cord injury was reproduced by modified Allen's method. Each group was given corresponding intervention treatment 2 hours after modeling. The electroacupuncture group was treated with electro-acupuncture at Jiaji (EX-B2) points in T8 to T12, the methylprednisolone group was given intraperitoneal injection of 30 mg/kg methylprednisolone sodium succinate, and the sham operation group and model group were not treated. After treatment, BBB scores were observed to evaluate the motor function of posterior limb in each group, and the injured spinal cord tissues were taken. The pathological changes of spinal cord neuropathy were observed by Nissl staining. The expression of microRNA-21 was detected by RT-qPCR, and the expression of apoptotic proteins (Bax, Bcl-2 and cleaved-Caspase-3) was detected by Western-Blot. Result:Compared with sham operation group, BBB, neuron survival rate and expression of microRNA-21 were significantly lower, apoptotic rate of neurons was significantly higher, expression of Bax, Bcl-2, cleaved Caspase-3 protein and Bax/Bcl-2 ratio were significantly increased in model group (P< 0.05). Electroacupuncture could significantly increase BBB score, neuron survival rate and expression of microRNA-21, reduce apoptotic rate of neurons and the ratio of Bax/Bcl-2, and inhibit the expression of Bax, Bcl-2 and cleaved Caspase-3 protein in tissues, which were significantly different from those of model group (P< 0.05). Conclusions: Electroacupuncture at Jiaji (EX-B2) points can significantly promote the recovery of neurological function in rats after ASCI, and its mechanism may be closely related to the up-regulation of the expression of microRNA-21 in tissues and the inhibition of the activation of Bax/Bcl-2/cleaved Caspase-3 signaling pathway.
基金supported by a grant from the Shaanxi Province Scientific and Technological Project in China,No.2014TM4193
文摘Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli(ST36),Xuanzhong(GB39),Futu(ST32)and Sanyinjiao(SP6)were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase(ACh E)activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor(GDNF)m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury.
基金supported by a grant from the Hunan Provincial Science and Technology Ministry in China, No. 2012SK3222Funding for New Teachers by the Ministry of Education in China, No. 200805331166
文摘The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Allen's method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also well recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additionally, anterior tibial muscle fibers slowly, but progressively, atrophied. Immu- nohistochemical staining showed that the absorbance values of calcitonin gene related peptide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic fi- broblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related peptide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through gene related peptide and acetylcholinesterase cord. attenuating the decreased expression of calcitonin n anterior horn motor neurons of the injured spinal
基金supported by the Study Science Foundation of the Department of Education, Yunnan Province, China, No. 2011Y184the National Natural Science Foundation of China, No. 10S090202+1 种基金Doctoral Innovation Foundation of Kunming Medical University, No. 2011D01the Natural Science Foundation of Kunming University, No. XJ11L016
文摘A contusive model of spinal cord injury at spinal segment T8-9 was established in rats. Huantiao (GB30) and Huatuojiaji (Ex-B05) were punctured with needles, and endogenous neural stem cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) and NG2. Double immunofluorescence staining showed that electroacupuncture markedly increased the numbers of BrdU+/NG2+cells at spinal cord tissue 15 mm away from the injury center in the rostral and caudal directions. The results suggest that electroacupuncture promotes the proliferation of endogenous neural stem cells and oligodendrocytes in rats with spinal cord injury.
基金supported by the Capital Characteristic Clinical Application Research Projects of Beijing Municipal Science and Technology Plan of China,No.Z16110000516009
文摘Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury.Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord.In this study,Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury.The rat models were established by inserting a balloon catheter into the atlanto-occipital space.The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression.Electroacupuncture was conducted at the acupoints Dazhui(GV14) and Baihui(GV 20)(2 Hz,15 minutes) once a day for 14 consecutive days.Compared with decompression alone,hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture.However,the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours.Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone.These findings indicate that compared with decompression alone,Governor Vessel electroacupuncture combined with delayed decompression(48 hours) is more effective in the treatment of upper cervical spinal cord injury.Governor Vessel electroacupuncture combined with early decompression(12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury.Nevertheless,further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone.
文摘OBJECTIVE: To formulate an evidence-based treatment for one patient with acute spinal cord injury and summarize evidence for evaluating acute spinal cord injury treatment. METHODS: Studies related to the treatment for acute spinal cord injury were identified via a search of National Guideline Clearinghouse (NGC, 2000 11), the Cochrane Library (Issue 1,2011), TRIP Database (2000 11), and PubMed (1966-2011). Treatment strategies were formulated according to three basic principles: best evidence, doctor's professional experience, and wishes of the patient. RESULTS: A total of 34 articles were selected, including 1 NGC guideline, 22 systematic reviews, and 11 randomized controlled trials. Based on our review, we arrived at the following recommendations: no clinical evidence exists definitively to recommend the use of any of neuroprotective pharmaceuticals; surgery should be undertaken early; mechanical compression devices and low-molecular weight heparin should be employed to prevent thrombosis; respiratory muscle training is beneficial for pulmonary function and quality of life; and functional electrical stimulation and acupuncture can promote functional recovery. The patient accordingly underwent surgery 6 hours after trauma without receiving any neuroprotective pharmaceuticals; low-molecular weight heparin and intermittent pneumatic compression were applied to prevent thrombosis. He also underwent respiratory muscle training daily for 8 weeks and received functional electrical stimulation for 15 minutes and acupuncture for 30 minutes every day. After follow-up for 3 months, the above therapeutic regimen was confirmed efficacious for acute spinal cord injury. CONCLUSION: Evidence-based medicine provides an individualized treatment protocol for acute spinal cord injury, which can significantly improve the therapeutic effect and prognosis.
文摘 Effect of acupuncture on free radicals after spinal cord injury was observed in rats with experimental spinal cord injury (SCI). Results indicated that within 24 hours after SCI malondialdehyde (MDA) increased progressively, 2 hours after SCI it reached the peak; and the superoxide dismutase (SOD) activity decreased significantly at the same hours, the decrease being the most marked 2-6 hours after SCI. The MDA content in the acupuncture group was significantly lower (P<0.05) and the SOD activity higher (P<0.01) than that of the control group respectively. It is suggested that acupuncture inhibits production of MDA and increases the SOD activity.……
基金National Natural Science Foundation of China(Nos.82174487 and 82205258)Zhejiang Medical and Health Science and Technology Plan Project(No.2021RC099)+2 种基金General scientific research project of Edu-cation Department of Zhejiang Province(No.Y202044576)Graduate Scientific Research Fund project of Zhejiang Chinese Medical Univer-sity(No.2022YKJ10)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents.
文摘Background:The inhibitory microenvironment around spinal cord injury(SCI)severely restricted functional repair after injury.Mitophagy was one of the important measures to maintain cellular homeostasis and ensure the harmonious nerve cell microenvironment.Hypoxia-inducible factor1α(HIF1-α)can mediate mitochondrial autophagy in neurodegenerative diseases,but the mechanisms are complex and diverse,which need to be further elucidated.Electroacupuncture plays a significant role in improving the neural microenvironment after spinal cord injury,promote long-term neurological function recovery in SCI patients,but whether electroacupuncture can participate in HIF1-α mediated mitophagy remains unknown.Objective:Investigated the effects of HIF1-α on mitochondrial autophagy in rats with spinal cord contusion and the potential mechanism of electroacupuncture.Methods:Following the successful construction of an SCI model of Sprague-Dawley rat utilizing a modified Allen method,electroacupuncture intervention was performed at T9 and T11 Jiaji acupoint(EX-B2),with further molecular biology and morphology examined by perfusion.To observe the effect of HIF1-α on local damage repair,the stereotypic injection of Hif1a knockdown virus was performed,and the changes of mitophagy in damaged local area was detected employing Western blotting,real-time fluorescence quantitative PCR,immunofluorescence,transmission electron microscopy and Nissl staining.Results:HIF1-α as well as its mitophagy receptor BNIP3 and NIX are upregulated after spinal cord injury.Elec-troacupuncture treatment or local inhibition of HIF1-α expression can reverse the early autophagy state after spinal cord injury,reduce cell apoptosis and injury area,promote neuronal survival.Conclusion:Electroacupuncture may serve as a promising strategy for spinal cord injury treatment,by alleviating HIF1-α mediated early mitochondrial autophagy.
基金Supported by State Key Program of National Natural Science Foundation of China,No.81330042Special Program for Sino-Russian Joint,Research Sponsored by the Ministry of Science and Technology,China,No.2014DFR31210+2 种基金Key Program Sponsored by the Tianjin Science and Technology Committee,China,No.14ZCZDSY00044National Natural Science Foundation of China,No.81201399National Natural Science Foundation of China,No.81301544
文摘The incidence of spinal cord injury(SCI) has been gradually increasing, and the treatment has troubled the medical field all the time. Primary and secondary injuries ultimately lead to nerve impulse conduction block. Microglia and astrocytes excessively accumulate and proliferate to form the glial scar. At present, to reduce the effect of glial scar on nerve regeneration is a hot spot in the research on the treatment of SCI. According to the preliminary experiments, we would like to provide a new bionic spinal cord to reduce the negative effect of glial scar on nerve regeneration. In this hypothesis we designed a new scaffold that combine the common advantage of acellular scaffold of spinal cord and thermosensitive gel, which could continue to release exogenous basic fibroblast growth factor(BFGF) in the spinal lesion area on the basis of BFGF modified thermosensitive gel. Meanwhile, the porosity, pore size and material of the gray matter and white matter regions were distinguished by an isolation layer, so as to induce the directed differentiation of cells into the defect site and promote regeneration of spinal cord tissue.
基金the National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100the National Natural Science Foundation of China(Key Program),No.81930070(both to SF)。
文摘Patients with potential spinal stenosis are susceptible to central cord syndrome induced by blunt trauma.Suitable animal models are helpful for studying the pathogenesis and treatment of such injuries.In this study,we established a mouse model of acute blunt traumatic spinal cord injury by compressing the C6 spinal cord with 5 and 10 g/mm~2 compression weights to simulate cervical central cord syndrome.Behavioral testing confirmed that this model exhibited the characteristics of central cord syndrome because motor function in the front paws was impaired,whereas basic motor and sensory functions of the lower extremities were retained.Hematoxylin-eosin staining showed that the diseased region of the spinal cord in this mouse model was restricted to the gray matter of the central cord,whereas the white matter was rarely affected.Magnetic resonance imaging showed a hypointense signal in the lesion after mild and severe injury.In addition,immunofluorescence staining showed that the degree of nerve tract injury in the spinal cord white matter was mild,and that there was a chronic inflammation reaction.These findings suggest that this mouse model of central cord syndrome can be used as a model for preclinical research,and that gray matter is most vulnerable to injury in central cord syndrome,leading to impaired motor function.