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 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.
Objective To explore the therapeutic effect of basic fibroblast growth factor (bFGF) on spinal cord injury (SCI) in rats and the influence of Notch/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods A total of 40 10-week-old male Sprague Dawley (SD) rats were selected to establish T10-segment SCI model by a free falling object. Among them, 32 successful models were randomly divided into model group and bFGF group, with 16 in each group. Another 16 SD rats were selected as sham-operation group, with only T10 processes, dura mater, and spinal cord exposed. After modeling, the rats in bFGF group were intraperitoneally injected with 100 μg/kg bFGF (once a day for 28 days), and the rats in model group and sham-operation group were injected with normal saline in the same way. The survival of rats in each group were observed after modeling. Basso-Beattie-Bresnahan (BBB) scores were performed before modeling and at immediate, 14 days, and 28 days after modeling to evaluate the functional recovery of hind limbs. Then, the spinal cord tissue at the site of injury was taken at 28 days and stained with HE, Nissl, and propidium iodide (PI) to observe the pathological changes, neuronal survival (number of Nissl bodies) and apoptosis (number of PI red stained cells) of the spinal cord tissue; immunohistochemical staining and ELISA were used to detect the levels of astrocyte activation markers [glial fibrillary acidic protein (GFAP)] and inflammatory factors [interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ)] in tissues, respectively. Western blot was used to detect the expressions of Notch/STAT3 signaling pathway related proteins [Notch, STAT3, phosphoryl-STAT3 (p-STAT3), bone morphogenetic protein 2 (BMP-2)] in tissues. Results All rats survived until the experiment was completed. At immediate after modeling, the BBB scores in model group and bFGF group significantly decreased when compared to sham-operation group (P<0.05). At 14 and 28 days after modeling, the BBB scores in model group significantly decreased when compared to sham-operation group (P<0.05); the bFGF group showed an increase compared to model group (P<0.05). Compared with before modeling, the BBB scores of model group and bFGF group decreased at immediate after modeling, and gradually increased at 14 and 28 days, the differences between different time points were significant (P<0.05). The structure of spinal cord tissue in sham-operation group was normal; in model group, there were more necrotic lesions in the spinal cord tissue and fewer Nissl bodies with normal structures; the number of necrotic lesions in the spinal cord tissue of the bFGF group significantly reduced compared to the model group, and some normally structured Nissl bodies were visible. Compared with sham-operation group, the number of Nissl bodies in spinal cord tissue significantly decreased, the number of PI red stained cells, GFAP, IL-1β, TNF-α, IFN-γ, Notch, p-STAT3 /STAT3, BMP-2 protein expression levels significantly increased in model group (P<0.05). The above indexes in bFGF group significantly improved when compared with model group (P<0.05). Conclusion bFGF can improve motor function and pathological injury repair of spinal cord tissue in SCI rats, improve neuronal survival, and inhibit neuronal apoptosis, excessive activation of astrocytes in spinal cord tissue and inflammatory response, the mechanism of which may be related to the decreased activity of Notch/STAT3 signaling pathway.
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.
ObjectiveTo assess whether expanding the landing zone of frozen elephant trunk (FET) increases the risk of spinal cord injury in patients with acute type A aortic dissection. MethodsPatients with acute type A aortic dissection who were treated in Guangdong Provincial People’s Hospital from 2017 to 2020 were collected. They were divided into two groups according to the landing zone of FET by the image diagnosis of postoperative chest X-ray or total aorta CT angiography, including a Th9 group which defined as below the eighth thoracic vertebral level, and a Th8 group which was defined as above or equal to the eighth thoracic vertebral level. Using the propensity score matching (PSM) method, the preoperative and intraoperative data of two groups were matched with a 1∶2 ratio. The prognosis of the two groups after PSM was analyzed. Results Before PSM, 573 patients were collected, including 58 patients in the Th9 group and 515 patients in the Th8 group. After PSM, 174 patients were collected, including 58 patients in the Th9 group (46 males and 12 females, with an average age of 47.91±9.92 years), and 116 patients in the Th8 group (93 males and 23 females, with an average age of 48.01±9.53 years). There were 8 patients of postoperative spinal cord injury in the two groups after PSM, including 5 (4.31%) patients in the Th8 group and 3 (5.17%) patients in the Th9 group (P=0.738). In the Th8 group, 2 patients had postoperative transient paresis and recovered spontaneously after symptomatic treatment, and 1 patient had postoperative paraplegia with cerebrospinal fluid drainage. After 3 days, the muscle strength of both lower limbs gradually recovered after treatment. There was no statistical difference in complications between the two groups (P＞0.05). ConclusionExpanding the landing zone of FET does not increase the risk of spinal cord injury in patients with acute type A aortic dissection. However, the sample size is limited, and in the future, multicenter large-scale sample size studies are still needed for verification
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.
Objective To investigate the effects of removing microglia from spinal cord on nerve repair and functional recovery after spinal cord injury (SCI) in mice. MethodsThirty-nine 6-week-old female C57BL/6 mice were randomly divided into control group (n=12), SCI group (n=12), and PLX3397+SCI group (n=15). The PLX3397+SCI group received continuous feeding of PLX3397, a colony-stimulating factor 1 receptor inhibitor, while the other two groups were fed a standard diet. After 14 days, both the SCI group and the PLX3397+SCI group were tested for ionized calcium binding adapter molecule 1 (Iba1) to confirm that the PLX3397+SCI group had completely depleted the spinal cord microglia. The SCI model was then prepared by clamping the spinal cord in both the SCI group and the PLX3397+SCI group, while the control group underwent laminectomy. Preoperatively and at 1, 3, 7, 14, 21, and 28 days postoperatively, the Basso Mouse Scale (BMS) was used to assess the hind limb function of mice in each group. At 28 days, a footprint test was conducted to observe the gait of the mice. After SCI, spinal cord tissue from the injury site was taken, and Iba1 immunofluorescence staining was performed at 7 days to observe the aggregation and proliferation of microglia in the spinal cord. HE staining was used to observe the formation of glial scars at the injury site at 28 days; glial fibrillary acidic protein (GFAP) immunofluorescence staining was applied to astrocytes to assess the extent of the injured area; neuronal nuclei antigen (NeuN) immunofluorescence staining was used to evaluate neuronal survival. And 5-hydroxytryptamine (5-HT) immunofluorescence staining was performed to assess axonal survival at 60 days. Results All mice survived until the end of the experiment. Immunofluorescence staining revealed that the microglia in the spinal cord of the PLX3397+SCI group decreased by more than 95% compared to the control group after 14 days of continuous feeding with PLX3397 (P<0.05). Compared to the control group, the BMS scores in the PLX3397+SCI group and the SCI group significantly decreased at different time points after SCI (P<0.05). Moreover, the PLX3397+SCI group showed a further decrease in BMS scores compared to the SCI group, and exhibited a dragging gait. The differences between the two groups were significant at 14, 21, and 28 days (P<0.05). HE staining at 28 days revealed that the SCI group had formed a well-defined and dense gliotic scar, while the PLX3397+SCI group also developed a gliotic scar, but with a more blurred and loose boundary. Immunofluorescence staining revealed that the number of microglia near the injury center at 7 days increased in the SCI group than in the control group, but the difference between groups was not significant (P>0.05). In contrast, the PLX3397+SCI group showed a significant reduction in microglia compared to both the control and SCI groups (P<0.05). At 28 days after SCI, the area of spinal cord injury in the PLX3397+SCI group was significantly larger than that in SCI group (P<0.05); the surviving neurons significantly reduced compared with the control group and SCI group (P<0.05). The axonal necrosis and retraction at 60 days after SCI were more obvious. ConclusionThe removal of microglia in the spinal cord aggravate the tissue damage after SCI and affecte the recovery of motor function in mice, suggesting that microglia played a neuroprotective role in SCI.
Objective To investigate the expression pattern of hypoxia-inducible factor 1α (HIF-1α) in experimental secondary spinal cord injury (SSCI) in rats and its potential effects on SSCI. Methods A total of 66 SD rats (female or male) with weight (250 ± 20) g were randomly divided into 3 groups: normal control group (group A, n=6), pseudo injury group (group B, n=6), and spinal cord injury (SCI) group (group C, n=54). In group A, no treatment was given as normal control. In groupB, only laminectomy was appl ied. In group C, laminectomy was appl ied and static compression model of SCI was built at T10 level. The expression of HIF-1α was measured with HE and immunohistochemical staining in groups A, B (1 hour after pseudo injury), and C (1, 3, 6, 12 hours and 1, 2, 3, 7, 14 days after SCI). Results All rats survived to the end of the experiment. HE staining showed that the spinal tissue of groups A and B were dense and the nucleus were round and big with l ight staining and clear nucleolus. The injured neuron at 1-12 hours after SCI of group C presented pyknosis and deep eosin staining. The swelling axon with bubbles and the disintegrated and disorganized medullary sheath in white matter appeared at 1-3 days after SCI. The hyperplasia of gl ial cells were obvious and gray matter cells were broken and apoptosis with cavities in injured spinal segment was observed at 7 and 14 days after SCI. Immunohistochemical staining showed that HIF-1α was poorly expressed in group A and increased a l ittle in group B. The positive expression in group C increased at 3 hours after SCI, which was found in spinal cord anterior horn neurons and a small amount of gangl ion cells. It reached peak at 1 day, maintained at a high level during 1-3 days and then decl ined. At 14 days, it appeared only in a small amount of gangl ion cells of white matter. There was no significant difference in the number of HIF-1α positive cells between groups A and B (t=1.325, P=0.137). The number of HIF-1α positive cells at each time point in group C was more than those in groups A and B (P lt; 0.05), and there were significant differences between all time points in group C (P lt; 0.05). Conclusion The expression of HIF-1α increases after SCI, it is related to the ischemia hypoxia after SSCI, and the expression pattern was correlated with the injury time.
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 To determine the feasibility, safety, and efficacy of common pedicle screw placement under direct vision combined with dome shaped decompression via small incision for double segment thoracolumbar fracture with nerve injury. Methods A retrospective analysis was performed on the clinical data of 32 patients with double segment thoracolumbar fracture with nerve injury undergoing common pedicle screw placement under direct vision combined with dome shaped decompression via small incision between November 2011 and November 2015 (combined surgery group), and another 32 patients undergoing traditional open pedicle screw fixation surgery (traditional surgery group). There was no significant difference in gender, age, cause of injury, time of injury-to-surgery, injury segments and Frankel classification of neurological function between two groups (P>0.05). The length of soft tissue dissection, the operative time, the blood loss during surgery, the postoperative drainage, the visual analogue scale (VAS) of incision after surgery, and recovery of neurological function after surgery were evaluated. Results All cases were followed up 9 to 12 months (mean, 10.5 months) in combined surgery group, and 8 to 12 months (mean, 9.8 months) in traditional surgery group. The length of soft tissue dissection, the operative time, the blood loss during surgery, the postoperative drainage, and the postoperative VAS score in the combined surgery group were significantly better than those in the traditional surgery group (P<0.05). Dural rupture during surgery and pedicle screw pulling-out at 6 months after surgery occurred in 2 cases and 1 case of the combined surgery group; dural rupture during surgery occurred in 1 case of the traditional surgery group. The X-ray films showed good decompression, and fracture healing; A certain degree of neurological function recovery was achieved in two groups. Conclusion Common pedicle screw placement under direct vision combined with dome shaped decompression via small incision can significantly reduce iatrogenic trauma and provide good nerve decompression. Therefore, it is a safe, effective, and minimally invasive treatment method for double segment thoracolumbar fracture with neurological injury.