Spinal cord injuries (SCI) in rodents have been created by laceration, contusion, compression, or intramedullary injection of toxic agents. The choice of an appropriate SCI model should be made for each study based ...Spinal cord injuries (SCI) in rodents have been created by laceration, contusion, compression, or intramedullary injection of toxic agents. The choice of an appropriate SCI model should be made for each study based on the experimental design, with care taken to avoid unintended complications such as hemorrhage. Technical comments will be made in this communication describing the 1) importance of vertebral stabi- lization, 2) injury preparation, and 3) landmarks to improve the preci- sion and reproducibility of the SCI.展开更多
The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis (ALS): ALS is a progressive neurological disease characterized primarily by the development of limb paralysis,...The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis (ALS): ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord (SC), where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis (mSOD1) and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging (DTI) has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy evaluate axonal structural changes at early stages of the disease in a preclinical model of ALS.展开更多
Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. I...Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies.展开更多
The duplication of animal models plays a key role in spinal cord injury research; however, there has been limited study into normal, external force-derived fracture dislocation. This study adopted experimental devices...The duplication of animal models plays a key role in spinal cord injury research; however, there has been limited study into normal, external force-derived fracture dislocation. This study adopted experimental devices, designed in-house, to construct standardized ventral and dorsal spinal cord injury animal models of 6 g and 17 g falling from a height of 2, 4, and 10 cm, and 15, 30 or 50 g transversal compression on the spinal cord. The results showed that gradual increases in the degree of histopathological injury led to decreased Tarlov and Basso, Beattie and Bresnahan scores for the behavioral test, and increased Ashworth scores for the hind limb. Furthermore, there was a gradual decline in the slope test in the rats with dorsal spinal cord injury that correlated to increases in the falling substance weight or falling height. Similar alterations were observed in the ventral spinal cord injured rats, proportional to the increase in compression weight. Our experimental findings indicate that the standardized experimental rat models of dorsal and ventral spinal cord injury are stable, reliable and reproducible.展开更多
Objective:Using neuromyelitis optica immunoglobulin G(NMO-IgG)to induced ex vivo mice spinal cord slice model.Methods:Vibratome-cut transverse spinal cord slices from 7-day-old C57BL/6Jmouse pups were cultured on tran...Objective:Using neuromyelitis optica immunoglobulin G(NMO-IgG)to induced ex vivo mice spinal cord slice model.Methods:Vibratome-cut transverse spinal cord slices from 7-day-old C57BL/6Jmouse pups were cultured on transwell porous supports for 7days,then randomly divided into the control group and NMO model group.Slices of the control group were further cultured with human serum complement,while slices from NMO model group were exposed to complement and NMO-IgG.After 24-hour incubation,slices of both groups were measured for aquaporin-4(AQP4),glial fibrillary acidic protein(GFAP),myelin basic protein(MBP)and neurofilament light chain(NFL)by immunofluorescence.Results:Slices exposed to NMO-IgG showed astrocyte swelling,and a significant loss of AQP4and GFAP staining.Ratios of the loss of AQP4and GFAP staining were 77.74%±6.75%and 75.62%±5.76%respectively in the model group,and NMO-like injury score was 3.11±0.60.But there were no obvious losses of AQP4and GFAP staining in the control group,and NMO-like lesion score was 0.00.There were significant differences between the two groups with regards to the above indexes(P<0.01).Ratios of the loss of MBP and NFL staining in the model group were 37.60%±4.88%and46.29%±4.98%respectively,while the corresponding figures in the control group were 9.10%±1.63%and 5.80%±0.81%,and the differences between the two groups were statistically significant(P<0.01).Conclusion:These results suggested that NMO-IgG-induced ex vivo spinal cord slice model possesses typical features of NMO,and this model might be useful for relevant fundamental studies.展开更多
The overall goal of this project is to develop a humane non-human primate model of traumatic spinal cord injury that will facilitate the development and evaluation of therapeutic interventions. The model utilizes neur...The overall goal of this project is to develop a humane non-human primate model of traumatic spinal cord injury that will facilitate the development and evaluation of therapeutic interventions. The model utilizes neurophysiological techniques to identify the location of the upper motor neuron axons that innervate the lower motor neurons that control tail musculature. This facilitates the placement of a selective lesion that partially disconnects the upper and lower motor neuron supply to the musculature of the tail. An implanted transmitter quantitatively measures electromyography data from the tail. The preliminary data indicates that this model is feasible. The subject was able to tolerate the implantation of the transmitter, without adverse effects. As well, there was no limb impairment, bowel dysfunction or bladder dysfunction. The histopathologic and electromyographic features of the selective experimental lesion were similar to human spinal cord injury.展开更多
Most animal spinal cord injury models involve a laminectomy,such as the weight drop model or the transection model.However,in clinical practice,many patients undergo spinal cord injury while maintaining a relatively c...Most animal spinal cord injury models involve a laminectomy,such as the weight drop model or the transection model.However,in clinical practice,many patients undergo spinal cord injury while maintaining a relatively complete spinal canal.Thus,open spinal cord injury models often do not simulate real injuries,and few previous studies have investigated whether having a closed spinal canal after a primary spinal cord injury may influence secondary processes.Therefore,we aimed to assess the differences in neurological dysfunction and pathological changes between rat spinal cord injury models with closed and open spinal canals.Sprague-Dawley rats were randomly divided into three groups.In the sham group,the tunnel was expanded only,without inserting a screw into the spinal canal.In the spinal cord injury with open canal group,a screw was inserted into the spinal canal to cause spinal cord injury for 5 minutes,and then the screw was pulled out,leaving a hole in the vertebral plate.In the spinal cord injury with closed canal group,after inserting a screw into the spinal canal for 5 minutes,the screw was pulled out by approximately 1.5 mm and the flat end of the screw remained in the hole in the vertebral plate so that the spinal canal remained closed;this group was the modified model,which used a screw both to compress the spinal cord and to seal the spinal canal.At 7 days post-operation,the Basso-Beattie-Bresnahan scale was used to measure changes in neurological outcomes.Hematoxylin-eosin staining was used to assess histopathology.To evaluate the degree of local secondary hypoxia,immunohistochemical staining and western blot assays were applied to detect the expression of hypoxia-inducible factor 1α(HIF-1α)and vascular endothelial growth factor(VEGF).Compared with the spinal cord injury with open canal group,in the closed canal group the Basso-Beattie-Bresnahan scores were lower,cell morphology was more irregular,the percentage of morphologically normal neurons was lower,the percentages of HIF-1α-and VEGF-immunoreactive cells were higher,and HIF-1αand VEGF protein expression was also higher.In conclusion,we successfully established a rat spinal cord injury model with closed canal.This model could result in more serious neurological dysfunction and histopathological changes than in open canal models.All experimental procedures were approved by the Institutional Animal Care Committee of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,China(approval No.HKDL201810)on January 30,2018.展开更多
The deleterious effect of vasculature damage on the outcome of spinal cord injury has long been recognized, and numerous clinical studies have shown that the presence of hemorrhage into the spinal cord is directly ass...The deleterious effect of vasculature damage on the outcome of spinal cord injury has long been recognized, and numerous clinical studies have shown that the presence of hemorrhage into the spinal cord is directly associated with a poorer neurological outcome. Vascular damage leads to de- creased blood flow to the cord and the release of potentially toxic blood-borne components. Here we consider the mechanisms that may be contributing to hemorrhage-induced damage and discuss the utility of a new model of spinal cord hemorrhage, which was urgently required as most of our current understanding has been extrapolated from intracerebral hemorrhage studies.展开更多
A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the ...A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the macaque fasicularis monkey that measures electromyographic data from the musculature of the tail. As well, previous experiments have demonstrated that selective lesions can be created in the lower thoracic spinal cord that does not cause limb weakness and/or bowel dysfunction. The histopathological features of these lesions appear similar to human TSCI. This paper describes a method by which the EMG data can be transformed into a quantitative metric of volitional limb movement (“Q”). This metric permits an objective assessment of injury, natural recovery as well as potential efficacy of candidate treatments.展开更多
Objective:To explore the modified Allen impactor method in establishing a rat model of spinal cord injury,and to preliminarily evaluate the motor function of the forelimbs and hindlimbs of rats.Methods:Thirty female S...Objective:To explore the modified Allen impactor method in establishing a rat model of spinal cord injury,and to preliminarily evaluate the motor function of the forelimbs and hindlimbs of rats.Methods:Thirty female SD rats with a body weight of 255±21g were randomly divided into two groups,namely the sham-operated group and the operated group,with 15 rats in each group.The spinal cord injury SD rat model was established by exposing but not injuring the spinal cord in the sham-operated group,while the SD rat model was established by the modified Allen impactor method in the operated group.The Basso-Beattie-Bresnahan(BBB)rating scale was used to assess the rats’hindlimb motor neurobehavior.A rat model of spinal cord injury was established by the modified Allen impactor method.After the cells were transplanted,the BBB score was used to evaluate the motor function;the changes in the motor function of rats with spinal cord injury were detected.Results:The motor function and sensory function of the forelimbs and hindlimbs of the rats showed significant changes after five days.The motor function of the forelimbs and hindlimbs of the rats in the sham-operated group were essentially normal after three days(about 20 points);the sensory function of the rats in the operated group decreased significantly after five days;however,in the sham-operated group,it decreased to 0.The motor function scores of the rats in the operated group at each point of time were significantly lower than those in the sham-operated group(p<0.05),while the forelimb motor function scores were significantly higher than those in the sham-operated group(p<0.05).Conclusion:The modified Allen impactor method that was used to establish a rat model of spinal cord injury in this study can significantly reduce the motor function of rats.展开更多
BACKGROUND: The establishment of a rat model of complete transected spinal cord injury lacks technological specifications. The current models lack concordance and reliability, and the death rate of the experimental a...BACKGROUND: The establishment of a rat model of complete transected spinal cord injury lacks technological specifications. The current models lack concordance and reliability, and the death rate of the experimental animals is high. Therefore, there is a great need for a reliable model to apply clinical applications of therapy. OBJECTIVE: To construct a rat model of complete transected spinal cord injury characterized by stability, reproducibility, and a high animal survival rate. DESIGN: Completely randomized controlled study. SETTING: Department of Neurosurgery, Xiangya Hospital of Central South University. MATERIALS: Fifty-five healthy specific pathogen free grade adult female Sprague Dawley rats were provided by the Experimental Animal Department, Xiangya Medical College, Central South University. Olympus BX51 imaging collecting analytic system was provided by Olympus Company, Japan; and SEN-7203 Nihon-Kohden electrical stimulator by Nihon Kohden, Japan. METHODS: This study was performed at the Laboratory of Neurosurgery, Xiangya Hospital of Central South University from April to June 2006. Experimental grouping: 55 rats were randomly divided into model group (n = 40) and sham surgery group (n = 15). In the model group, a self-made sliver hook was passed through the ventral side to support the spinal cord at the T12 segment and to shear it off. A complete transected spinal cord, 2 mm in length, was resected. In the sham surgery group, the spinal cord was identically exposed. The dura mater of the spinal cord was cut open, but the spinal cord was not damaged. MAIN OUTCOME MEASURES: Histopathological changes after spinal cord injury at L2 segment were observed subsequent to hematoxylin and eosin staining under optical microscopy. Olympus BX51 imaging collecting analytic system was used to count spinal cord ventral horn neurons. Motor function of rat hindlimb was evaluated with the Basso, Beattie and Bresnahan (BBB) scale. Paraplegia was evaluated as 0 point, and complete normality as 21 points. Somatosensory-evoked potential was measured using Nihon-Kohden electric stimulator at 21 days post-operation. RESULTS: A total of 82% (33/40) rats survived longer than 30 days after modeling. Pathological changes of spinal cord tissue: degenerative and necrotic pathological changes appeared in the model group after surgery; for example, neuronal swelling, chromatinolysis, and karyopyknosis. The spinal cord in the sham surgery group displayed mild edema 24 hours after surgery, gradually recovering to normal levels. Quantification of spinal cord ventral horn neurons: the number of spinal cord ventral horn neurons in the model group was less than in the sham surgery group at 24 hours, as well as 7 and 21 days after surgery (P 〈 0.01); while, the number at 7 and 21 days after surgery decreased compared to 24 hours after surgery (P 〈 0.01). Motor function changes: Rats in the sham operation group moved lightly abnormally following anesthesia recovery and then moved normally 7 days after surgery. BBB scores in the model group were less than in the sham surgery group 21 days after surgery (P 〈 0.01). BBB scores of both lower extremities increased slightly 7 days after surgery (P 〈 0.01); however, voluntary motor function of both lower extremities was still not recovered 30 days after surgery. Changes of somatosensory-evoked potential: wave form of somatosensory-evoked potential was normal in the sham surgery group 21 days after surgery, but recovered wave form was not recorded in the model group. CONCLUSION: Results from spinal cord histopathology, cytology, motor function, and somatosensory-evoked potential suggested that the complete transected spinal cord injury model in this study was stable, reliable, and reproducible. Furthermore, the survival rate of experimental animals was high.展开更多
The purpose of this present work is to provide a tool to better understand mechanically related pathologies of the lumbar unit and the spinal structure by providing spinal cord deformations in different loading cases....The purpose of this present work is to provide a tool to better understand mechanically related pathologies of the lumbar unit and the spinal structure by providing spinal cord deformations in different loading cases. In fact, spinal cord injury (SCI) resulting from a traumatic movement leades to a deformation of the neural and vascular structure of the spinal cord. And since the magnitude of the spinal cord stress is correlated with the pressure of the vertebral elements, stresses will be computed on all theses components. Physical properties of the vertebrae, various ligaments, the discs, and the spinal cord are described under simple loading as compression, and combined loading, flexion and lateral bending to evaluate the pressure undergone by different components of the lumbar unit. A nonlinear three-dimensional finite element method is used as a numerical tool to perform all the computations. This study provides accurate results for the localisation and the magnitude of maximum equivalent stress and shear stress on the lumbar unit and especially for the spinal cord. These results showed that stresses are more important when a compression of 500 N is combined with a flexion and a lateral bending. In particular, shear stresses are maximum for the spinal cord and the four intervertebral discs for the case of a flexion of 3.8 N.m and a lateral bending of 6.5 N.m.展开更多
Some studies have suggested that early surgical treatment can effectively improve the prognosis of cervical spinal cord injury without radiological abnormality, but no research has focused on the development of a prog...Some studies have suggested that early surgical treatment can effectively improve the prognosis of cervical spinal cord injury without radiological abnormality, but no research has focused on the development of a prognostic model of cervical spinal cord injury without radiological abnormality. This retrospective analysis included 43 patients with cervical spinal cord injury without radiological abnormality. Seven potential factors were assessed: age, sex, external force strength causing damage, duration of disease, degree of cervical spinal stenosis, Japanese Orthopaedic Association score, and physiological cervical curvature. A model was established using multiple binary logistic regression analysis. The model was evaluated by concordant profiling and the area under the receiver operating characteristic curve. Bootstrapping was used for internal validation. The prognostic model was as follows: logit(P) =-25.4545 + 21.2576 VALUE + 1.2160SCORE-3.4224 TIME, where VALUE refers to the Pavlov ratio indicating the extent of cervical spinal stenosis, SCORE refers to the Japanese Orthopaedic Association score(0–17) after the operation, and TIME refers to the disease duration(from injury to operation). The area under the receiver operating characteristic curve for all patients was 0.8941(95% confidence interval, 0.7930–0.9952). Three factors assessed in the predictive model were associated with patient outcomes: a great extent of cervical stenosis, a poor preoperative neurological status, and a long disease duration. These three factors could worsen patient outcomes. Moreover, the disease prognosis was considered good when logit(P) ≥-2.5105. Overall, the model displayed a certain clinical value. This study was approved by the Biomedical Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University, China(approval number: 2018063) on May 8, 2018.展开更多
Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chlorid...Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.展开更多
Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using c...Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using contusion or complete transection models and this has led to a deeper understanding of the molecular and cellular complexities of the injury. However, it has not to date led to development of successful novel therapies, this is in part due to the complexity of the injury and the difficulty of deciphering the exact roles and interactions of different cells within this complex environment. Here we developed a collagen matrix that can be molded into the 3D tubular shape with a lumen and can hence support cell interactions in a similar architecture to a spinal cord. We show that astrocytes can be successfully grown on this matrix in vitro and when injured, the cells respond as they do in vivo and undergo reactive gliosis, one of the steps that lead to formation of a glial scar, the main barrier to spinal cord regeneration. In the future, this system can be used to quickly assess the effect of drugs on glial scar protein activity or to perform live imaging of labeled cells after exposure to drugs.展开更多
文摘Spinal cord injuries (SCI) in rodents have been created by laceration, contusion, compression, or intramedullary injection of toxic agents. The choice of an appropriate SCI model should be made for each study based on the experimental design, with care taken to avoid unintended complications such as hemorrhage. Technical comments will be made in this communication describing the 1) importance of vertebral stabi- lization, 2) injury preparation, and 3) landmarks to improve the preci- sion and reproducibility of the SCI.
基金provided by the Chicago Biomedical Consortium’s Postdoctoral Research Award,No.085740
文摘The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis (ALS): ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord (SC), where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis (mSOD1) and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging (DTI) has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy evaluate axonal structural changes at early stages of the disease in a preclinical model of ALS.
文摘Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies.
基金the National Natural Science Foundation of China for Youths, No.30901483the Natural Science Foundation of Shanxi Province for Youths,No. 2009021041-3Projects of Patent Promoteand Implementation of Shanxi Province, No.111009
文摘The duplication of animal models plays a key role in spinal cord injury research; however, there has been limited study into normal, external force-derived fracture dislocation. This study adopted experimental devices, designed in-house, to construct standardized ventral and dorsal spinal cord injury animal models of 6 g and 17 g falling from a height of 2, 4, and 10 cm, and 15, 30 or 50 g transversal compression on the spinal cord. The results showed that gradual increases in the degree of histopathological injury led to decreased Tarlov and Basso, Beattie and Bresnahan scores for the behavioral test, and increased Ashworth scores for the hind limb. Furthermore, there was a gradual decline in the slope test in the rats with dorsal spinal cord injury that correlated to increases in the falling substance weight or falling height. Similar alterations were observed in the ventral spinal cord injured rats, proportional to the increase in compression weight. Our experimental findings indicate that the standardized experimental rat models of dorsal and ventral spinal cord injury are stable, reliable and reproducible.
基金supported by the National Natural Science Foundation of China (No.81460194 No.81260188)
文摘Objective:Using neuromyelitis optica immunoglobulin G(NMO-IgG)to induced ex vivo mice spinal cord slice model.Methods:Vibratome-cut transverse spinal cord slices from 7-day-old C57BL/6Jmouse pups were cultured on transwell porous supports for 7days,then randomly divided into the control group and NMO model group.Slices of the control group were further cultured with human serum complement,while slices from NMO model group were exposed to complement and NMO-IgG.After 24-hour incubation,slices of both groups were measured for aquaporin-4(AQP4),glial fibrillary acidic protein(GFAP),myelin basic protein(MBP)and neurofilament light chain(NFL)by immunofluorescence.Results:Slices exposed to NMO-IgG showed astrocyte swelling,and a significant loss of AQP4and GFAP staining.Ratios of the loss of AQP4and GFAP staining were 77.74%±6.75%and 75.62%±5.76%respectively in the model group,and NMO-like injury score was 3.11±0.60.But there were no obvious losses of AQP4and GFAP staining in the control group,and NMO-like lesion score was 0.00.There were significant differences between the two groups with regards to the above indexes(P<0.01).Ratios of the loss of MBP and NFL staining in the model group were 37.60%±4.88%and46.29%±4.98%respectively,while the corresponding figures in the control group were 9.10%±1.63%and 5.80%±0.81%,and the differences between the two groups were statistically significant(P<0.01).Conclusion:These results suggested that NMO-IgG-induced ex vivo spinal cord slice model possesses typical features of NMO,and this model might be useful for relevant fundamental studies.
文摘The overall goal of this project is to develop a humane non-human primate model of traumatic spinal cord injury that will facilitate the development and evaluation of therapeutic interventions. The model utilizes neurophysiological techniques to identify the location of the upper motor neuron axons that innervate the lower motor neurons that control tail musculature. This facilitates the placement of a selective lesion that partially disconnects the upper and lower motor neuron supply to the musculature of the tail. An implanted transmitter quantitatively measures electromyography data from the tail. The preliminary data indicates that this model is feasible. The subject was able to tolerate the implantation of the transmitter, without adverse effects. As well, there was no limb impairment, bowel dysfunction or bladder dysfunction. The histopathologic and electromyographic features of the selective experimental lesion were similar to human spinal cord injury.
文摘Most animal spinal cord injury models involve a laminectomy,such as the weight drop model or the transection model.However,in clinical practice,many patients undergo spinal cord injury while maintaining a relatively complete spinal canal.Thus,open spinal cord injury models often do not simulate real injuries,and few previous studies have investigated whether having a closed spinal canal after a primary spinal cord injury may influence secondary processes.Therefore,we aimed to assess the differences in neurological dysfunction and pathological changes between rat spinal cord injury models with closed and open spinal canals.Sprague-Dawley rats were randomly divided into three groups.In the sham group,the tunnel was expanded only,without inserting a screw into the spinal canal.In the spinal cord injury with open canal group,a screw was inserted into the spinal canal to cause spinal cord injury for 5 minutes,and then the screw was pulled out,leaving a hole in the vertebral plate.In the spinal cord injury with closed canal group,after inserting a screw into the spinal canal for 5 minutes,the screw was pulled out by approximately 1.5 mm and the flat end of the screw remained in the hole in the vertebral plate so that the spinal canal remained closed;this group was the modified model,which used a screw both to compress the spinal cord and to seal the spinal canal.At 7 days post-operation,the Basso-Beattie-Bresnahan scale was used to measure changes in neurological outcomes.Hematoxylin-eosin staining was used to assess histopathology.To evaluate the degree of local secondary hypoxia,immunohistochemical staining and western blot assays were applied to detect the expression of hypoxia-inducible factor 1α(HIF-1α)and vascular endothelial growth factor(VEGF).Compared with the spinal cord injury with open canal group,in the closed canal group the Basso-Beattie-Bresnahan scores were lower,cell morphology was more irregular,the percentage of morphologically normal neurons was lower,the percentages of HIF-1α-and VEGF-immunoreactive cells were higher,and HIF-1αand VEGF protein expression was also higher.In conclusion,we successfully established a rat spinal cord injury model with closed canal.This model could result in more serious neurological dysfunction and histopathological changes than in open canal models.All experimental procedures were approved by the Institutional Animal Care Committee of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,China(approval No.HKDL201810)on January 30,2018.
基金supported by a grant from Medical Research Council,No.MRCG0300456
文摘The deleterious effect of vasculature damage on the outcome of spinal cord injury has long been recognized, and numerous clinical studies have shown that the presence of hemorrhage into the spinal cord is directly associated with a poorer neurological outcome. Vascular damage leads to de- creased blood flow to the cord and the release of potentially toxic blood-borne components. Here we consider the mechanisms that may be contributing to hemorrhage-induced damage and discuss the utility of a new model of spinal cord hemorrhage, which was urgently required as most of our current understanding has been extrapolated from intracerebral hemorrhage studies.
文摘A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the macaque fasicularis monkey that measures electromyographic data from the musculature of the tail. As well, previous experiments have demonstrated that selective lesions can be created in the lower thoracic spinal cord that does not cause limb weakness and/or bowel dysfunction. The histopathological features of these lesions appear similar to human TSCI. This paper describes a method by which the EMG data can be transformed into a quantitative metric of volitional limb movement (“Q”). This metric permits an objective assessment of injury, natural recovery as well as potential efficacy of candidate treatments.
基金Natural Science Basic Research Program of Shaanxi Province(Project Number:S2019-JC-YB-1575)。
文摘Objective:To explore the modified Allen impactor method in establishing a rat model of spinal cord injury,and to preliminarily evaluate the motor function of the forelimbs and hindlimbs of rats.Methods:Thirty female SD rats with a body weight of 255±21g were randomly divided into two groups,namely the sham-operated group and the operated group,with 15 rats in each group.The spinal cord injury SD rat model was established by exposing but not injuring the spinal cord in the sham-operated group,while the SD rat model was established by the modified Allen impactor method in the operated group.The Basso-Beattie-Bresnahan(BBB)rating scale was used to assess the rats’hindlimb motor neurobehavior.A rat model of spinal cord injury was established by the modified Allen impactor method.After the cells were transplanted,the BBB score was used to evaluate the motor function;the changes in the motor function of rats with spinal cord injury were detected.Results:The motor function and sensory function of the forelimbs and hindlimbs of the rats showed significant changes after five days.The motor function of the forelimbs and hindlimbs of the rats in the sham-operated group were essentially normal after three days(about 20 points);the sensory function of the rats in the operated group decreased significantly after five days;however,in the sham-operated group,it decreased to 0.The motor function scores of the rats in the operated group at each point of time were significantly lower than those in the sham-operated group(p<0.05),while the forelimb motor function scores were significantly higher than those in the sham-operated group(p<0.05).Conclusion:The modified Allen impactor method that was used to establish a rat model of spinal cord injury in this study can significantly reduce the motor function of rats.
基金the Scientific and Technological Foundation of Hunan Public Health Bureau, No. B2006-034
文摘BACKGROUND: The establishment of a rat model of complete transected spinal cord injury lacks technological specifications. The current models lack concordance and reliability, and the death rate of the experimental animals is high. Therefore, there is a great need for a reliable model to apply clinical applications of therapy. OBJECTIVE: To construct a rat model of complete transected spinal cord injury characterized by stability, reproducibility, and a high animal survival rate. DESIGN: Completely randomized controlled study. SETTING: Department of Neurosurgery, Xiangya Hospital of Central South University. MATERIALS: Fifty-five healthy specific pathogen free grade adult female Sprague Dawley rats were provided by the Experimental Animal Department, Xiangya Medical College, Central South University. Olympus BX51 imaging collecting analytic system was provided by Olympus Company, Japan; and SEN-7203 Nihon-Kohden electrical stimulator by Nihon Kohden, Japan. METHODS: This study was performed at the Laboratory of Neurosurgery, Xiangya Hospital of Central South University from April to June 2006. Experimental grouping: 55 rats were randomly divided into model group (n = 40) and sham surgery group (n = 15). In the model group, a self-made sliver hook was passed through the ventral side to support the spinal cord at the T12 segment and to shear it off. A complete transected spinal cord, 2 mm in length, was resected. In the sham surgery group, the spinal cord was identically exposed. The dura mater of the spinal cord was cut open, but the spinal cord was not damaged. MAIN OUTCOME MEASURES: Histopathological changes after spinal cord injury at L2 segment were observed subsequent to hematoxylin and eosin staining under optical microscopy. Olympus BX51 imaging collecting analytic system was used to count spinal cord ventral horn neurons. Motor function of rat hindlimb was evaluated with the Basso, Beattie and Bresnahan (BBB) scale. Paraplegia was evaluated as 0 point, and complete normality as 21 points. Somatosensory-evoked potential was measured using Nihon-Kohden electric stimulator at 21 days post-operation. RESULTS: A total of 82% (33/40) rats survived longer than 30 days after modeling. Pathological changes of spinal cord tissue: degenerative and necrotic pathological changes appeared in the model group after surgery; for example, neuronal swelling, chromatinolysis, and karyopyknosis. The spinal cord in the sham surgery group displayed mild edema 24 hours after surgery, gradually recovering to normal levels. Quantification of spinal cord ventral horn neurons: the number of spinal cord ventral horn neurons in the model group was less than in the sham surgery group at 24 hours, as well as 7 and 21 days after surgery (P 〈 0.01); while, the number at 7 and 21 days after surgery decreased compared to 24 hours after surgery (P 〈 0.01). Motor function changes: Rats in the sham operation group moved lightly abnormally following anesthesia recovery and then moved normally 7 days after surgery. BBB scores in the model group were less than in the sham surgery group 21 days after surgery (P 〈 0.01). BBB scores of both lower extremities increased slightly 7 days after surgery (P 〈 0.01); however, voluntary motor function of both lower extremities was still not recovered 30 days after surgery. Changes of somatosensory-evoked potential: wave form of somatosensory-evoked potential was normal in the sham surgery group 21 days after surgery, but recovered wave form was not recorded in the model group. CONCLUSION: Results from spinal cord histopathology, cytology, motor function, and somatosensory-evoked potential suggested that the complete transected spinal cord injury model in this study was stable, reliable, and reproducible. Furthermore, the survival rate of experimental animals was high.
文摘The purpose of this present work is to provide a tool to better understand mechanically related pathologies of the lumbar unit and the spinal structure by providing spinal cord deformations in different loading cases. In fact, spinal cord injury (SCI) resulting from a traumatic movement leades to a deformation of the neural and vascular structure of the spinal cord. And since the magnitude of the spinal cord stress is correlated with the pressure of the vertebral elements, stresses will be computed on all theses components. Physical properties of the vertebrae, various ligaments, the discs, and the spinal cord are described under simple loading as compression, and combined loading, flexion and lateral bending to evaluate the pressure undergone by different components of the lumbar unit. A nonlinear three-dimensional finite element method is used as a numerical tool to perform all the computations. This study provides accurate results for the localisation and the magnitude of maximum equivalent stress and shear stress on the lumbar unit and especially for the spinal cord. These results showed that stresses are more important when a compression of 500 N is combined with a flexion and a lateral bending. In particular, shear stresses are maximum for the spinal cord and the four intervertebral discs for the case of a flexion of 3.8 N.m and a lateral bending of 6.5 N.m.
基金supported by the National Natural Science Foundation of China,No.30672136(to HPL)
文摘Some studies have suggested that early surgical treatment can effectively improve the prognosis of cervical spinal cord injury without radiological abnormality, but no research has focused on the development of a prognostic model of cervical spinal cord injury without radiological abnormality. This retrospective analysis included 43 patients with cervical spinal cord injury without radiological abnormality. Seven potential factors were assessed: age, sex, external force strength causing damage, duration of disease, degree of cervical spinal stenosis, Japanese Orthopaedic Association score, and physiological cervical curvature. A model was established using multiple binary logistic regression analysis. The model was evaluated by concordant profiling and the area under the receiver operating characteristic curve. Bootstrapping was used for internal validation. The prognostic model was as follows: logit(P) =-25.4545 + 21.2576 VALUE + 1.2160SCORE-3.4224 TIME, where VALUE refers to the Pavlov ratio indicating the extent of cervical spinal stenosis, SCORE refers to the Japanese Orthopaedic Association score(0–17) after the operation, and TIME refers to the disease duration(from injury to operation). The area under the receiver operating characteristic curve for all patients was 0.8941(95% confidence interval, 0.7930–0.9952). Three factors assessed in the predictive model were associated with patient outcomes: a great extent of cervical stenosis, a poor preoperative neurological status, and a long disease duration. These three factors could worsen patient outcomes. Moreover, the disease prognosis was considered good when logit(P) ≥-2.5105. Overall, the model displayed a certain clinical value. This study was approved by the Biomedical Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University, China(approval number: 2018063) on May 8, 2018.
基金supported by a grant from Guangzhou Medical University,No.2008C24
文摘Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.
文摘Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using contusion or complete transection models and this has led to a deeper understanding of the molecular and cellular complexities of the injury. However, it has not to date led to development of successful novel therapies, this is in part due to the complexity of the injury and the difficulty of deciphering the exact roles and interactions of different cells within this complex environment. Here we developed a collagen matrix that can be molded into the 3D tubular shape with a lumen and can hence support cell interactions in a similar architecture to a spinal cord. We show that astrocytes can be successfully grown on this matrix in vitro and when injured, the cells respond as they do in vivo and undergo reactive gliosis, one of the steps that lead to formation of a glial scar, the main barrier to spinal cord regeneration. In the future, this system can be used to quickly assess the effect of drugs on glial scar protein activity or to perform live imaging of labeled cells after exposure to drugs.