Objective To explore the construction of a canine model of vascularized allogeneic spinal cord transplantation (vASCT) and preliminarily evaluate its therapeutic efficacy for spinal cord injury (SCI). Methods Sixteen female Beagle dogs aged 8-12 months were randomly selected, with 8 dogs serving as donors for the harvesting of spinal cord tissue with a vascular pedicle [dorsal intercostal artery (DIA) at the T10 level and accompanying vein]. The remaining 8 dogs underwent a 1.5-cm-length spinal cord defect at the T10 level, followed by transplantation of the donor spinal cord tissue for repair. Polyethylene glycol (PEG) was applied to both ends to spinal cord graft; then, using a random number table method, the dogs were divided into an experimental group (n=4) and a control group (n=4). The experimental group received immunosuppressive intervention with oral tacrolimus [0.1 mg/(kg∙d)] postoperatively, while the control group received no treatment. The operation time and ischemia-reperfusion time of two groups were recorded. The recovery of hind limb function was estimated by Olby score within 2 months after operation; the motor evoked potentials (MEP) was measured through neuroelectrophysiological examination, and the spinal cord integrity was observed through MRI. ResultsThere was no significant difference in the operation time and ischemia-reperfusion time between the two groups (P>0.05). All dogs survived until the completion of the experiment. Within 2 months after operation, all dogs in the control group failed to regain the movement function of hind limbs, and Olby scores were all 0. In the experimental group, the movement and weight-bearing, as well as walking abilities of the hind limbs gradually recovered, and the Olby scores also showed a gradually increasing trend. There was a significant difference between the two groups from 3 to 8 weeks after operation (P<0.05). Neuroelectrophysiological examination indicated that the electrical signals of the experimental group passed through the transplanted area, and the latency was shortened compared to that at 1 month after operation (P<0.05), showing continuous improvement, but the amplitude did not show significant improvement (P>0.05). The control group was unable to detect any MEP changes after operation. MRI examination showed that the transplanted spinal cord in the experimental group survived and had good continuity with normal spinal cord tissue, while no relevant change was observed in the control group. ConclusionThe vASCT model of dogs was successfully constructed. This surgical procedure can restore the continuity of the spinal cord. The combination of tacrolimus anti-immunity is a key factor for the success of transplantation.
ObjectiveTo evaluate whether long frozen elephant trunk (FET) increases the risk of spinal cord injury in patients with acute type A aortic dissection.MethodsFrom 2018 to 2019, 172 patients with acute type A aortic dissection were treated in Guangdong Provincial People’s Hospital. They were divided into two groups according to the length of FET: patients treated with stents of 100 mm in length were enrolled into a short FET group, and those with stents of 150 mm in length into a long FET group. There were 124 patients in the short FET group, including 108 (87.1%) males and 16 (12.9%) females with a mean age of 51.8±7.9 years. There were 48 patients in the long FET group, including 44 (91.7%) males and 4 (8.3%) females with a mean age of 50.6±9.7 years. The clinical data and prognosis of the patients were analyzed.ResultsThe mean distal stent graft was at the level of T 8.5±0.7 in the long FET group, and at the level of T 6.8±0.6 in the short FET group (P=0.001). Sixteen patients died after operation in the two groups, including 13 (10.5%) in the short FET group and 3 (6.2%) in the long FET group (P=0.561). There were 7 patients of spinal cord injury in the two groups, including 6 (4.8%) in the short FET group and 1 (2.2%) in the long FET group (P=0.675). There was no statistical difference in other complications between the two groups. The follow-up time was 16.7 (1-30) months. During the follow-up, 2 patients died in the long FET group and 5 died in the short FET group. No new spinal cord injury or distal reintervention occurred during the follow-up.ConclusionLong FET does not increase the incidence of spinal cord injury in patients with acute type A aortic dissection.
The capacity of embryonic spinal cord tissue in the repair of injured structure of spinal cord has been noted for years. In order to investigate the embryonic spinal cord graft in the repair of motor function of injured spinal cord, the embryonic spinal cord tissue was transplanted to the hemisection cavity in spinal cord in adult rat. One hundred adult Wistar Rats were used to simulate the hemisectional injury of spinal cord by drilling 2-3 mm cavity in lumbar enlargement. Sixty rats were treated with rat embryonic spinal cord tissue grafting while the other forty were chosen as control. The outcome was evaluated according the combined behavioural score (CBS) and motor evoked potential (MEP) in the 1, 2, 4 and 12 weeks. The grafting group was superior to the control as assessed by CBS (P lt; 0.05), especially within 4 weeks. (P lt; 0.01). The restoration of the latent peak of early wave(P1, N1) was better in the grafting group, too. This suggested that embryonic spinal cord graft could improve the recovery of motor function of injured spinal cord in adult rat. The effect of the embryonic spinal cord tissue graft might be concerned with its secretion of several kinds of neurotrophic factors, nerve growth factor, nerve transmitted factor, or adjustment of hormone.
Objective To evaluate the feasibility and safety of percutaneous endoscopic technique in the treatment of intraspinal cement leakage after percutaneous vertebroplasty (PVP). Methods Between May 2014 and March 2016, 5 patients with lower limb pain and spinal cord injury caused by intraspinal cement leakage after PVP, were treated with percutaneous endoscopic spinal decompression. Of 5 cases, 3 were male and 2 were female, aged from 65 to 83 years (mean, 74.4 years). The course of disease was 10-30 days (mean, 16.2 days). Imageological examinations confirmed the levels of cement leakage at T 12, L 1 in 3 cases, and at L 1, 2 in 2 cases; bilateral sides were involved in 1 case and unilateral side in 4 cases. Two patients had lower limb pain, whose visual analogue scale (VAS) were 8 and 7; 3 patients had lower extremities weakness, whose Japanese Orthopedic Association (JOA) 29 scores were 18, 20, and 19. According to American Spinal Injury Association (ASIA) impairment scale, neural function was rated as grade E in 2 cases and grade D in 3 cases. Results The operation time was 55-119 minutes (mean, 85.6 minutes), and the blood loss was 30-80 mL (mean, 48 mL). CT scan and three-dimensional (3D) reconstruction at 1 day after operation showed that cement leakage was removed in all patients. Five cases were followed up 6-21 months (mean, 12 months). In 2 patients with lower limb pain, and VAS score was significantly decreased to 2 at last follow-up. In 3 patients with lower extremities weakness, the muscle strength was improved progressively, and the JOA29 scores at last follow-up were 21, 23, and 22. Conclusion Percutaneous endoscopic technique for intraspinal cement leakage after PVP is safe, effective, and feasible.
Clinical trials have demonstrated that kilohertz-frequency transcutaneous spinal cord stimulation (TSCS) can be used to facilitate the recovery of sensory-motor function for patients with spinal cord injury, whereas the neural mechanism of TSCS is still undetermined so that the choice of stimulation parameters is largely dependent on the clinical experience. In this paper, a finite element model of transcutaneous spinal cord stimulation was used to calculate the electric field distribution of human spinal cord segments T12 to L2, whereas the activation thresholds of spinal fibers were determined by using a double-cable neuron model. Then the variation of activation thresholds was obtained by varying the carrier waveform, the interphase delay, the modulating frequency, and the modulating pulse width. Compared with the sinusoidal carrier, the usage of square carrier could significantly reduce the activation threshold of dorsal root (DR) fibers. Moreover, the variation of activation thresholds was no more than 1 V due to the varied modulating frequency and decreases with the increased modulating pulse width. For a square carrier at 10 kHz modulated by rectangular pulse with the frequency of 50 Hz and the pulse width of 1 ms, the lowest activation thresholds of DR fibers and dorsal column fibers were 27.6 V and 55.8 V, respectively. An interphase delay of 5 μs was able to reduce the activation thresholds of the DR fibers to 20.1 V. The simulation results can lay a theoretical foundation on the selection of TSCS parameters in clinical trials.
Spine is a common site of metastasis in patients with malignant tumors, and tumor metastasis to the spine can lead to pain, pathological fractures, and nerve compression. In order to optimize the diagnosis and management of patients with spinal metastases and metastatic spinal cord compression (MSCC), the National Institute for Health and Care Excellence (NICE) in the UK proposed the first diagnostic and treatment guidelines for patients with MSCC (or at risk of MSCC) in 2008. In recent years, with the rapid advancement of spinal surgery and radiotherapy technology, the standardized process of MSCC diagnosis and treatment urgently needs to be updated. In 2023, NICE launched new guidelines for spinal metastases and MSCC. Based on a thorough study of the guidelines, this article discusses and interprets pain management, corticosteroid treatment, application of bisphosphonates and denosumab, tools for assessing spinal stability and prognosis, radiation therapy, surgical timing and approach, etc., providing reference for clinical diagnosis and treatment in China.
Objective Aminoguanidine (AG) can reduce brain edema and increase the recovery of neuron functions in surgical brain injury and stroke. To investigate the effect of AG on spinal cord injury (SCI) in rats and its mechanism. Methods A total of 150 adult male Sprague Dawley rats (weighing, 230-255 g) were divided into control group (group A, 25 rats without treatment), the sham-operated group (group B, 25 rats undergoing laminectomy), SCI group (group C, 25 SCI rats with injection of 5%DMSO), SCI + AG groups (groups D, E, and F, 25 SCI rats and AG injection of 75, 150, and 300 mg/kg, respectively). The optimal dosage of AG was screened by dry-wet weight method with the percentage of water content at 0, 12, 24, and 48 hours after injury. The blood-spinal cord barriar permeability was further detected by Evans blue (EB) method, aquaporins 4 (AQP4) mRNA expression by RT-PCR, AQP4 protein expression by immunohistochemistry and Western blot. Results AG injection at dosage of 150 mg/kg can significantly reduce edema of spinal cords at 12, 24, and 48 hours after SCI (P lt; 0.05), so 150 mg/kg was the optimal dosage. The EB content in group E was significantly lower than that in group C at 12, 24, and 48 hours after SCI, and the permeability of blood-spinal cord barrier was significantly decreased compared with group C (P lt; 0.05). The AQP4 mRNA expressions in groups B and E were significantly lower than that in group C at 12, 24, and 48 hours after SCI (P lt; 0.05). AQP4 protein expressions in groups B and E were significantly lower than that in group C at 24 and 48 hours after SCI (P lt; 0.05) by Western blot. Immunohistochemical staining revealed that AQP4 protein expression in group C was significantly higher than that in groups B and E (P lt; 0.05) at 48 hours after SCI, but no significant difference was found between group B and group E (P gt; 0.05). Conclusion AG injection at dosage of 150 mg/kg can induce spinal cord edema and injury in rats, which could be correlated with the down-regulation of AQP4 expression.
Spinal cord stimulation (SCS) for pain is usually implanted as an open loop system using unchanged parameters. To avoid the under and over stimulation caused by lead migration, evoked compound action potentials (ECAP) is used as feedback signal to change the stimulating parameters. This study established a simulation model of ECAP recording to investigate the relationship between ECAP component and dorsal column (DC) fiber recruitment. Finite element model of SCS and multi-compartment model of sensory fiber were coupled to calculate the single fiber action potential (SFAP) caused by single fiber in different spinal cord regions. The synthetized ECAP, superimposition of SFAP, could be considered as an index of DC fiber excitation degree, because the position of crests and amplitude of ECAP corresponds to different fiber diameters. When 10% or less DC fibers were excited, the crests corresponded to fibers with large diameters. When 20% or more DC fibers were excited, ECAP showed a slow conduction crest, which corresponded to fibers with small diameters. The amplitude of this slow conduction crest increased as the stimulating intensity increased while the amplitude of the fast conduction crest almost remained unchanged. Therefore, the simulated ECAP signal in this paper could be used to evaluate the degree of excitation of DC fibers. This SCS-ECAP model may provide theoretical basis for future clinical application of close loop SCS base on ECAP.
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.
Spina bifida and tethered spinal cord are congenital diseases that can lead to severe disability. At present, most doctors in relevant specialties in China still have insufficient understanding of spina bifida, resulting in high incidence and aggravation of its complications. To provide guidance for the diagnosis and treatment of spina bifida and tethered spinal cord in China, experts from neurosurgery, urology, orthopedics, spine surgery, and rehabilitation departments who have experiences in the diagnosis and treatment of spina bifida discussed and summarized their experiences, and referred to the relevant literature on the diagnosis and treatment of spina bifida at home and abroad. Expert consensus was formed in the following aspects: concept, classification, and pathological changes of spina bifida; diagnosis; treatment process and operation timing; principles and methods of treatment; rehabilitation; and follow up. This expert consensus can provide reference for relevant care providers of spina bifida in China.