Spinal cord injury (SCI) is a complex pathological process. Based on the encouraging results of preclinical experiments, some stem cell therapies have been translated into clinical practice. Mesenchymal stem cells (MSCs) have become one of the most important seed cells in the treatment of SCI due to their abundant sources, strong proliferation ability and low immunogenicity. However, the survival rate of MSCs transplanted to spinal cord injury is rather low, which hinders its further clinical application. In recent years, hydrogel materials have been widely used in tissue engineering because of their good biocompatibility and biodegradability. The treatment strategy of hydrogel combined with MSCs has made some progress in SCI repair. This review discusses the significance and the existing problems of MSCs in the repair of SCI. It also describes the research progress of hydrogel combined with MSCs in repairing SCI, and prospects its application in clinical research, aiming at providing reference and new ideas for future SCI treatment.
In order to observe the role of genetically modified Schwann cell (SC) with pSVP0Mcat in the regeneration of injured spinal cord, the cells were implanted into the spinal cord. Ninety SD rats were used to establish a model of hemi-transection of spinal cord at the level of T8, and were divided into three groups, randomly, that is, pSVP0Mcat modified SC implantation (Group A), SC implantation (Group B) and without cell implantation as control (Group C). After three months the presence of axonal regeneration of the injured spinal cord was examined by means of horseradish peroxidase (HRP) retrograde labelling technique and stereography. The results indicated that HRP labelled cells in Group A and B could be found in the superior region of injured spinal cord and the brain stem such as the red nuclei and oculomotor nuclei. The density of ventral hom neurons of the spinal cord and the number of myelinated axons in 100 microns of the white matter was A gt; B gt; C group. In brief, the pSVP0Mcat modified SC intraspinal implantation could promote regeneration of the injured spinal cord.
Objective To discuss the clinical characteristics, mechanism, and treatment of odontoid fracture combined with lower cervical spinal cord injuries without fracture or dislocation. Methods According to the inclusion and exclusion criteria, 7 male patients aged 37-71 years (mean, 51.4 years), suffered from odontoid fractures combined with lower cervical spinal cord injuries without fracture or dislocation were analyzed retrospectively between June 2007 and October 2015. The trauma causes were traffic accidents in 2 cases, fall in 2 cases, and hit injury in 3 cases. The time from injury to admission was 2 hours to 3 days with an average of 9 hours. According to Anderson-Grauer classification of odontoid fracture, 1 case of type IIA, 3 cases of type IIB, 2 cases of type IIC, and 1 case of shallow type III were found. The cervical spinal cord injuries affected segments included C4, 5 in 1 case, C4–6 in 2 cases, and C5–7 in 4 cases. All the cervical spine had different degenerative changes: 2 of mild, 3 of moderate, and 2 of severe. The lower cervical spinal cord injury was assessed by Sub-axial Injury Classification (SLIC) with scoring of 4-6 (mean, 5.1). The visual analogue scale (VAS) score was used to evaluate the occipital neck pain with scoring of 7.8±1.0; the neurological function was assessed by American Spinal Injury Association (ASIA) as grade B in 1 case, grade C in 4 cases, and grade D in 2 cases; and Japanese Orthopedic Association score (JOA) was 9.2±3.9. For the odontoid fractures, 4 cases were fixed with anterior screw while the others were fixed with posterior atlantoaxial fixation and fusion. For the lower cervical spine, 4 cases were carried out with anterior cervical corpectomy and titanium fusion while the others with anterior cervical disecotomy and Cage fusion. Results The operation time was 178-252 minutes (mean, 210.2 minutes); the intraoperative blood loss was 60-140 mL (mean, 96.5 mL) and with no blood transfusion. All incisions healed primarily. All the patients were followed up 12-66 months (mean, 18 months). There was no direct surgical related complications during operation, and all bone grafting got a fusion at 6-9 months (mean, 7.7 months) after operation. There was no inter-fixation failure or loosening. At last follow-up, the VAS score declined to 1.7±0.7 and JOA score improved to 15.1±1.7, showing significant differences when compared with preoperative ones (t=18.064, P=0.000; t=–7.066, P=0.000). The neurological function of ASIA grade were also improved to grade D in 5 cases and grade E in 2 cases, showing significant difference (Z=–2.530, P=0.011). Conclusion Complex forces and degeneration of lower cervical spine were main reasons of odontoid fracture combined with lower cervical spinal cord injuries without fracture or dislocation. The type of odontoid fracture and neurological deficit status of lower cervical spinal cord were important to guide making strategy of one-stage operation with a satisfactory clinic outcome.
ObjectiveTo explore the effectiveness of functional reconstruction of hand grasp and pinch by tendon transfers in patients with cervical spinal cord injury.MethodsBetween July 2013 and January 2016, tendon transfer surgery were performed in 21 patients (41 hands) with cervical spinal injury that motion level was located at C6 to reconstruct hand grasp and pinch function. There were 18 males and 3 females with a mean age of 42.3 years (range, 17-65 years). Nineteen patients were with complete spinal cord injury [American Spinal Injury Association (ASIA) grading A], 1 patient was with central cord syndrome whose bilateral hands were completely paralyzed and lower limbs were normal (ASIA grading D), and 1 patient was with cervical spondylotic myelopathy (AISA grading D). The time from injury to hospitalization was 12-22 months (mean, 16.8 months). According to the International classification of surgery of the hand in tetraplegia (ICSHT), there were 6 cases of grade O3, 10 of grade O4, 3 of grade OCu5, and 2 of grade O5. The surgery was divided into two stages with an interval of 6-11 months. At the first stage, grip function was reconstructed in all patients by transfering the extensor carpi radialis longus from radialis side to palmar side through subcutaneous tunnel, and braided and sutured with the flexor pollicis longus and flexor digitorum profundus. At the second stage, the lateral pinch function of the thumb and index finger was reconstructed by braiding and suturing the radial half of the extensor carpi ulnaris (the patients graded as ICSHT O3) or pronator tere (the patients graded above ICSHT O3) with extensor pollicis longus and abductor pollicis longus. The grasp force, the thumb and index finger lateral pinch force, and the maximum fingertips distance between the thumb and index finger were measured at preoperation and at different time points after operation. The modified Lamb and Chan questionnaire, based upon the activities of daily living, was used to evaluate the hand function of all patients at 6 months after sencond stage surgery.ResultsThere was 1 patient with elbow skin lesion, 1 patient with wrist stiffness; both of them recovered after corresponding treatment. All the 21 patients were followed up 15-32 months (mean, 19.6 months) without wound infection, tendon adhesion, tendon rupture, and other complications. The grasp forces of all patients were significantly improved at 4 weeks, 3 months, 6 months, and 1 year after the first stage surgery when compared with preoperative value (P<0.05); and no significant difference was found between different time points after operation (P>0.05). The thumb and index finger lateral pinch force and the maximum fingertips distance between the thumb and index finger of all patients were also significantly improved at 4 weeks, 3 months, 6 months, and 1 year after the second stage surgery when compared with preoperative values (P<0.05); and no significant difference was found between different time points after operation (P>0.05). And there was no significant difference of above indexes between the patients graded as ICSHT O3 and above ICSHT O3 (P>0.05). The functional outcome was good in 19 cases, fair in 1 case, and poor in 1 case according to modified Lamb and Chan questionnaire at 6 months after second stage surgery.ConclusionTendon transfer can significantly improve the hand function and the quality of life of the patients with complete cervical spinal cord injury.
Objective To explore the factors to affect severity of hyperextension injury of the cervical spinal cord (HEICSC). Methods Forty-five patients with HEICSC, 35 males and 10 females, aged 27-67 years old (mean 48.2 years old), were retrospectively analyzed. The disease course was 30 minutes to 16 days. According to modified Frankel grading, there were 6 cases of grade A, 8 cases of grade B, 16 cases of grade C and 15 cases of grade D. Spinal cord injuries (SCI) segments were determined according to SCI plane and high signal change (HSC) in spinal cord on MR images. The whole or large part of HSC segments were supposed to be main injured spinal cord segments (MISCSs) and the staccato or patchy HSC ones were supposed to be common injured spinal cord segments (CISCSs). When the external force acting on head or face suffered was larger, the force produced during high-speed movement or forehead and/or face had severe contused and/or) lacerated wound, the force was defined severe traumatic strength, whereas the reverse was true for sl ight traumatic strength. According to signal magnitude of the cervical discs on T2-weighted MR images, degeneration of cervical discs and cervical vertebras were classified into 5 grades: grade 0-4. Cervical spinal stenosis were graded to 5 grades according to the width of anterior or posterior cerebrospinal fluid layer to spinal cord on T2-weighted MR images and compressed degree of spinal cord on T1-weighted MR images. The influence of traumatic strength, cervical spinal degeneration or cervical spinal stenosis on SCI were explored. Results Among the 45 cases, 12 cases were caused by sl ight traumatic strength, 33 cases were caused by severe one. The cervical spinal cord was injuried more sl ightly and the patients were older in the sl ight traumatic strength cases than in the severe ones (P lt; 0.05). The number of MISCSs were 45 in 40 cases and the 25 segments were located at C3, 4 level. The number of CISCSs were 39 in 21 cases. All the cervical vertebraes of the 45 patients had degenerated. The most were in grade 3 in 22 patients and the severest degenerative segments were mostly located in C5,6 discs in 35 ones. The number of the MISCSs in different degenerative grades of discs was 0 in grade 0, 9 in grade 1, 20 in grade 2, 14 in grade 3, and 2 in grade 4. The ratios of the segment number of injuried spinal cord to the segment number of spinal stenosis in every grade of stenosis were 1/62 in grade 0, 2/11 in grade 1, 27/52 in grade 2, 33/33 in grade 3, 21/22 in grade 4. Conclusion Three main factors including the magnitude of traumatic strength, the degree of instabil ity of cervical vertebrae and the degree of cervical stenosis contribute to development and progress of HEICSC.
ObjectiveTo study the effects of astaxanthin on the apoptosis after spinal cord injury in rats.MethodsOne hundred and forty-four healthy adult Sprague Dawley rats were divided into experimental group, control group, and sham group according to the random number table (n=48). In the control group and the experimental group, the modified Allen’s method was used to make the spinal cord injury model; in the sham group, only the lamina was cut without damaging the spinal cord. At immediate after operation, the rats in the experimental group were given intragastric administration of astaxanthin (75 mg/kg) twice a day; and the rats in the control group and the sham group were given equal amount of olive oil by gavage twice a day. BBB score was used to assess the motor function at 1 day and 1, 2, 3, and 4 weeks after operation. The malondialdehyde (MDA) content was determined by the thiobarbituric acid method at 24 hours after operation; and the activity of superoxide dismutase (SOD) was determined by the xanthine oxidase method. Apoptosis index (AI) was determined by TUNEL method at 6, 24, and 48 hours after operation. At 48 hours after operation, the water content of spinal cord was measured by dry-wet weight method, the lesion ratio of spinal cord was calculated, the ultrastructure of the spinal cord was observed by transmission electron microscopy, and ultrastructure scoring was performed using the Kaptanoglu score method.ResultsThe BBB score in the control group and the experimental group was significantly lower than that in the sham group at each postoperative time point (P<0.05); and the BBB score in the experimental group were significantly higher than that in the control group at 1-4 weeks postoperatively (P<0.05). The MDA content in the control group and the experimental group was significantly higher than that in the sham group at 24 hours after operation, and in the experimental group was significantly lower than in the control group (P<0.05). The SOD activity in the control group and the experimental group was significantly lower than that in the sham group, and in the experimental group was significantly higher than in the control group (P<0.05). At each time point postoperatively, the AI in the control group and the experimental group was significantly higher than that in the sham group, and in the experimental group was significantly lower than in the control group (P<0.05). At 48 hours after operation, the water content of spinal cord, the lesion ratio of spinal cord, and the ultrastructure score in the control group and the experimental group were significantly higher than those in the sham group, and in the experimental group were significantly lower than in the control group (P<0.05).ConclusionAstaxanthin can inhibit the lipid peroxidation, reduce the apoptosis, reduce the spinal cord edema, reduce the spinal cord lesion, reduce the histopathological damage after spinal cord injury, and improve the motor function of rats with spinal cord injury, and protect the spinal cord tissue, showing an obvious neuroprotective effect.
ObjectiveTo investigate the effect of saikosaponin a (SSa) on the levels of immune inflammation in rats with acute spinal cord injury and its possible mechanism.MethodsSeventy-two Sprague Dawley rats (weighing, 220-250 g) were randomly divided into sham operation group (group A), spinal cord injury group (group B), and SSa treatment group (group C) respectively, 24 rats in each group. The spinal cord injury model was induced by using the Allen’s method in groups B and C; the spinous process and vertebral plate at both sides were cut off by lamina excision to expose the spinal cord in group A. The rats were given intraperitoneal injection of 10 mg/kg SSa in group C and equal volume of normal saline in group B at immediate after injury. The spinal cord tissue was harvested from 18 rats of each group at 24 hours after operation to measure the levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) by ELISA, to detect the expressions of nuclear factor κB (NF-κB) P65, NF-κB P-P65, and aquaporin 4 (AQP4) by Western blot and to observe the morphology of spinal cord by HE staining. The motor function of the lower limbs was evaluated by BBB score and tiltboard experiment in 6 rats at 1, 3, 7, 14, 21, and 28 days after injury.ResultsThe BBB score and tiltboard experiment maximum angle were significantly higher in group A than groups B and C at each time point (P<0.05) and in group C than group B at 14, 21, and 28 days after operation (P<0.05). ELISA test showed that the concentrations of TNF-α and IL-6 were significantly lower in group A than groups B and C, and in group C than group B (P<0.05). Western blot results showed that the protein expression levels of NF-κB P65, NF-κB P-P65, and AQP4 were significantly lower in group A than groups B and C, and in group C than group B (P<0.05). HE staining demonstrated normal neurons of the spinal cord and no obvious lesion in group A; neuronal cells were observed in the injured area of group B, with hemorrhage, neutrophil infiltration, and nerve cell edema in the injured area; the neuronal cells were visible in the spinal cord of group C, with microglia mild hyperplasia, and the pathological changes were improved when compared with group B.ConclusionSSa has neuroprotective effects on acute spinal cord injury in rats by inhibiting NF-κB signaling pathway and AQP4 protein expression and reducing inflammation response and edema.
Objective To explore the related factors of upper urinary tract deterioration (UUTD) in spinal cord injury patients using intermittent catheterization (IC-SCI) in the community. Methods Patients with spinal cord injury in the Chinese community were selected for investigation between August 3 and August 31, 2020. The included patients were divided into UUTD group and non-UUTD group. The basic information, intermittent catheterization practices, and urinary complications were compared between the two groups. Logistic regression was used to analyze the risk factors contributing to UUTD. Results A total of 431 patients were surveyed. Among them, there were 310 males and 121 females, 246 cases in the non-UUTD group and 185 cases in the UUTD group. There were statistically significant differences in the disease duration, gender, etiology, urinary incontinence, urinary tract infection, bladder calculi and nephrolithiasis between the two groups (P<0.05); there was no statistically significant difference in the other indicators between the two groups (P>0.05). The results of logistic regression analysis showed that urinary tract infection [odds ratio (OR)=3.229, 95% confidence interval (CI) (1.706, 6.110), P<0.001], nephrolithiasis [OR=4.846, 95%CI (2.617, 8.973), P<0.001], and urinary incontinence [OR=2.345, 95%CI (1.116, 4.925), P=0.024] were risk factors for UUTD. Conclusion Urinary tract infection, nephrolithiasis and urinary incontinence are independent risk factors for UUTD in community-based IC-SCI patients and deserve attention for preventive strategies.
OBJECTIVE Following the delayed repair of peripheral nerve injury, the cell number of anterior horn of the spinal cord and its ultrastructural changes, motorneuron and its electrophysiological changes were investigated. METHODS In 16 rabbits the common peroneal nerves of both sides being transected one year later were divided into four groups randomly: the degeneration group and regeneration of 1, 3 and 5 months groups. Another 4 rabbits were used for control. All transected common peroneal nerves underwent epineural suture except for the degeneration group the electrophysiological examination was carried out at 1, 3 and 5 months postoperatively. Retrograde labelling of the anterior horn cells was demonstrated and the cells were observed under light and electronmicroscope. RESULTS 1. The number of labelled anterior horn cell in the spinal cord was 45% of the normal population after denervation for one year (P lt; 0.01). The number of labelled cells increased steadily from 48% to 57% and 68% of normal values at 1, 3 and 5 months following delayed nerve repair (P lt; 0.01). 2. The ultrastructure of the anterior horn cells of the recover gradually after repair. 3. With the progress of regeneration the latency become shortened, the conduction velocity was increased, the amplitude of action potential was increased. CONCLUSION Following delayed repair of injury of peripheral nerve, the morphology of anterior horn cells of spinal cord and electrophysiological display all revealed evidence of regeneration, thus the late repair of injury of peripheral nerve was valid.
ObjectiveTo investigate the expression changes and the repair effect of mitogen and stress- activated protein kinase 1 (MSK1) on spinal cord injury (SCI) in rats.MethodsOne hundred and twenty male Sprague Dawley (SD) rats (weighing 220-250 g) were used for the study, 70 of them were randomly divided into sham-operation group and SCI group (n=35), the rats in SCI group were given SCI according to Allen’s method, and the sham-operation group only opened the lamina without injuring the spinal cord; spinal cord tissue was collected at 8 hours, 12 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after invasive treatment, each group of 5 rats was used to detect the expression of MSK1 and proliferating cell nuclear antigen (PCNA) by Western blot assay. Another 20 SD rats were grouped by the same method as above (n=10). In these rats, a negative control lentiviral LV3NC dilution was injected at a depth of approximately 0.8 mm at the spinal cord T10 level. The results of transfection at 1, 3, 5, 7, and 14 days after injection were observed under an inverted fluorescence microscope to determine the optimal transfection time of the virus. The other 30 SD rats were randomly divided into group A with only SCI, group B with a negative control lentiviral LV3NC injected after SCI, and group C with MSK1 small interfering RNA (siRNA) lentivirus injected after SCI, with 10 rats each group. The Basso, Beatlie, Bresnahan (BBB) score of hind limbs was measured at 1, 3, 5, 7, and 14 days after treatment; spinal cord tissue collected at the optimal time point for lentivirus transfection was detected the expression changes of MSK1 and PCNA by Western blot and the localization by immunofluorescence staining of MSK1 and PCNA proteins.ResultsWestern blot assay showed that there was no significant changes in the expression of MSK1 and PCNA at each time points in the sham-operation group. In the SCI group, the expression of MSK1 protein was gradually decreased from 8 hours after injury to the lowest level at 3 days after injury, and then gradually increased; the expression change of PCNA protein was opposite to MSK1. The expression of MSK1 in SCI group was significantly lower than that in the sham-operation group at 1, 2, 3, and 5 days after injury (P<0.05), and the expression of PCNA protein of SCI group was significantly higher than that of the sham-operation group at 8 hours and 1, 2, 3, 5, and 7 days after injury (P<0.05). The fluorescence expression of both the SCI group and the sham-operation group has be found and peaked at 7 days. There was a positive correlation between fluorescence intensity and time in 7 days after transfection. With the prolongation of postoperative time, the BBB scores of groups A, B, and C showed a gradually increasing trend. The BBB score of group C was significantly lower than those of groups A and B at 5, 7, and 14 days after treatment (P<0.05). After transfection for 7 days, Western blot results showed that the relative expression of MSK1 protein in group C was significantly lower than that in groups A and B (P<0.05); and the relative expression of PCNA protein was significantly higher than that in groups A and B (P<0.05). Immunofluorescence staining showed that MSK1 was expressed in the nuclei of the spinal cord and colocalized with green fluorescent protein, neuronal nuclei, and glial fibrillary acidic protein (GFAP). The relative expression area of MSK1 positive cells in group C was significantly higher than that in group B (P<0.05), and the relative expression areas of PCNA and GFAP positive cells were significantly lower than those in group B (P<0.05).ConclusionLentivirus-mediated MSK1 siRNA can effectively silence the expression of MSK1 in rat spinal cord tissue. MSK1 may play a critical role in the repair of SCI in rats by regulating the proliferation of glial cells.