This study aims to investigate the neuroprotective effect of tetramethylpyrazine on mice after spinal cord injury and its mechanism. Seventy-five female C57BL/6 mice were randomly divided into 5 groups, namely, a sham operation group, a model group, a tetramethylpyrazine low-dose group(25 mg·kg~(-1)), a tetramethylpyrazine medium-dose group(50 mg·kg~(-1)), and a tetramethylpyrazine high-dose group(100 mg·kg~(-1)), with 15 mice in each group. Modified Rivlin method was used to establish the mouse model of acute spinal cord injury. After 14 d of tetramethylpyrazine intervention, the motor function of hind limbs of mice was evaluated by basso mouse scale(BMS) and inclined plate test. The levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) in the spinal cord homogenate were determined by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe the histology of the spinal cord, and Nissl's staining was used to observe the changes in the number of neurons. Western blot and immunofluorescence method were used to detect the expression of glial fibrillary acidic protein(GFAP) and C3 protein. Tetramethylpyrazine significantly improved the motor function of the hind limbs of mice after spinal cord injury, and the BMS score and inclined plate test score of the tetramethylpyrazine high-dose group were significantly higher than those of the model group(P<0.01). The levels of TNF-α, IL-6, and IL-1β in spinal cord homogenate of the tetramethylpyrazine high-dose group were significantly decreased(P<0.01). After tetramethylpyrazine treatment, the spinal cord morphology recovered, the number of Nissl bodies increased obviously with regular shape, and the loss of neurons decreased. As compared with the model group, the expression of GFAP and C3 protein was significantly decreased(P<0.05,P<0.01) in tetramethylpyrazine high-dose group. In conclusion, tetramethylpyrazine can promote the improvement of motor function and play a neuroprotective role in mice after spinal cord injury, and its mechanism may be related to inhibiting inflammatory response and improving the hyperplasia of glial scar.
Rats ; Mice ; Female ; Animals ; Rats, Sprague-Dawley ; Neuroprotective Agents/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; Mice, Inbred C57BL ; Spinal Cord Injuries/genetics* ; Spinal Cord/metabolism*

OBJECTIVE: To summarize the research progress of stem cell transplantation in treating spinal cord injury (SCI) at different stages based on the pathophysiological mechanism of SCI. METHODS: The relevant research literature at home and abroad was extensively reviewed to explore the impact of transplantation timing on the effectiveness of stem cell transplantation in treating SCI. RESULTS: Researchers performed different types of stem cell transplantation for subjects at different stages of SCI through different transplantation approaches. Clinical trials have proved the safety and feasibility of stem cell transplantation at acute, subacute, and chronic stages, which can alleviate inflammation at the injured site and restore the function of the damaged nerve cells. But the reliable clinical trials comparing the effectiveness of stem cell transplantation at different stages of SCI are still lacking. CONCLUSION Stem cell transplantation has a good prospect in treating SCI. In the future, the multi-center, large sample randomized controlled clinical trials are needed, with a focus on the long-term effectiveness of stem cell transplantation.
Humans ; Hematopoietic Stem Cell Transplantation ; Neurons ; Recovery of Function/physiology* ; Spinal Cord ; Spinal Cord Injuries/surgery* ; Stem Cell Transplantation

PURPOSE: To identify risk factors for developing pressure ulcers (PUs) in the acute care period of traumatic spinal fracture patients with or without spinal cord injuries (SCIs). METHODS: Data were collected prospectively in participating the National Spinal column/Cord Injury Registry of Iran (NSCIR-IR) from individuals with traumatic spinal fractures with or without SCIs, inclusive of the hospital stay from admission to discharge. Trained nursing staff examined the patients for the presence of PUs every 8 h during their hospital stay. The presence and grade of PUs were assessed according to the European Pressure Ulcer Advisory Panel classification. In addition to PU, following data were also extracted from the NSCIR-IR datasets during the period of 2015 - 2021: age, sex, Glasgow coma scale score at admission, having SCIs, marital status, surgery for a spinal fracture, American Spinal Injury Association impairment scale (AIS), urinary incontinence, level of education, admitted center, length of stay in the intensive care unit (ICU), hypertension, respiratory diseases, consumption of cigarettes, diabetes mellitus and length of stay in the hospital. Logistic regression models were used to estimate the unadjusted and adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Altogether 2785 participants with traumatic spinal fractures were included. Among them, 87 (3.1%) developed PU during their hospital stay and 392 (14.1%) had SCIs. In the SCI population, 63 (16.1%) developed PU during hospital stay. Univariate logistic regression for the whole sample showed that marital status, having SCIs, urinary incontinence, level of education, treating center, number of days in the ICU, age, and Glasgow coma scale score were significant predictors for PUs. However, further analysis by multiple logistic regression only revealed the significant risk factors to be the treating center, marital status, having SCIs, and the number of days in the ICU. For the subgroup of individuals with SCIs, marital status, AIS, urinary incontinence, level of education, the treating center, the number of days in the ICU and the number of days in the hospital were significant predictors for PUs by univariate analysis. After adjustment in the multivariate model, the treating center, marital status (singles vs. marrieds, OR = 3.06, 95% CI: 1.55 - 6.03, p = 0.001), and number of days in the ICU (OR = 1.06, 95% CI: 1.04 - 1.09, p < 0.001) maintained significance. CONCLUSIONS These data confirm that individuals with traumatic spinal fractures and SCIs, especially single young patients who suffer from urinary incontinence, grades A-D by AIS, prolonged ICU stay, and more extended hospitalization are at increased risk for PUs; as a result strategies to minimize PU development need further refinement.
Humans ; Spinal Fractures/etiology* ; Pressure Ulcer/complications* ; Iran/epidemiology* ; Spinal Cord Injuries/epidemiology* ; Risk Factors ; Spine ; Registries ; Urinary Incontinence/complications* ; Suppuration/complications*

OBJECTIVES: To investigate the effect of torso training on unstable surface on lower limb motor function in patients with incomplete spinal cord injury. METHODS: A total of 80 patients with incomplete spinal cord injury caused by thoracolumbar fracture admitted in Ningbo Yinzhou No.2 Hospital from April 2020 to December 2021 were randomly divided into control group and study group, with 40 cases in each group. In addition to routine training, the control group received torso training on stable surface and the study group received torso training on unstable surface. The gait, lower limb muscle strength, balance function, lower limb function, mobility and nerve function of the two groups were compared. RESULTS: After treatment, the stride length, stride frequency and comfortable walking speed improved in the two groups (all P<0.05), and the improvements in study group were more significant (all P<0.05). The muscle strength of quadriceps femoris, gluteus maximus, hamstring, anterior tibialis and gastrocnemius were improved in the two groups (all P<0.05), and the improvements in study group were more significant (all P<0.05); the total trajectories of static eye opening and static eye closing gravity center movement in the two groups were significantly shorter (all P<0.05), and the improvements in the study group were more significant (all P<0.05). The dynamic stability limit range and the American Spinal Injury Association (ASIA) lower extremity motor score, Berg balance scale, modified Barthel index scale in the two groups were significantly higher (all P<0.05), and these scores in study group were significantly higher than those in the control group (all P<0.05). Both groups showed a significant improvement in ASIA grade (all P<0.05), and the improvement in the study group was significantly better (P<0.05). CONCLUSIONS Torso training on unstable surface can effectively improve the gait and lower limb muscle strength of patients with incomplete spinal cord injury and improve the lower limb motor function.
Humans ; Walking/physiology* ; Spinal Cord Injuries ; Gait/physiology* ; Lower Extremity ; Torso

Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17⁺ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17⁺ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.
Animals ; Rats ; Interleukin-17 ; Rats, Sprague-Dawley ; Recovery of Function ; Spinal Cord Injuries/drug therapy* ; T-Lymphocytes, Regulatory ; Receptors, Antigen, T-Cell, gamma-delta/immunology*

Humans ; Poliomyelitis/diagnosis* ; Fractures, Bone ; Lower Extremity ; Spinal Cord Injuries/diagnosis*

OBJECTIVE: To investigate the effect of acetylcorynoline (Ace) for promoting functional recovery of injured spinal cord in rats and explore the underlying mechanism. METHODS: Rat models of spinal cord injury (SCI) were treated with intraperitoneal injection of different concentrations of Ace, with the sham-operated rats as the control group. After the treatment, the changes in motor function of the rats and the area of spinal cord injury were assessed with BBB score and HE staining, and the changes in pro-inflammatory cytokine levels and microglial activation were determined using PCR, ELISA and immunofluorescence staining. In a lipopolysaccharide (LPS)-treated BV2 cell model, the effects of different concentrations of Ace or DMSO on microglial activation and inflammatory cytokine production were observed. Network pharmacology analysis was performed to predict the target protein and signaling mechanism that mediated the inhibitory effect of Ace on microglia activation, and AutoDock software was used for molecular docking between Ace and the target protein. A signaling pathway blocker (Osimertinib) was used to verify the signaling mechanism in rat models of SCI and LPS-treated BV2 cell model. RESULTS: In rat models of SCI, Ace treatment significantly increased the BBB score, reduced the area of spinal cord injury, and lowered the number of activated microglia cells and the levels of pro-inflammatory cytokines (P < 0.05). The cell experiments showed that Ace treatment significantly lower the level of cell activation and the production of inflammatory cytokines in LPS-treated BV2 cells (P < 0.05). Network pharmacology analysis suggested that EGFR was the main target of Ace, and they bound to each other via hydrogen bonds as shown by molecular docking. Western blotting confirmed that Ace inhibited the activation of the EGFR/MAPK signaling pathway in injured mouse spinal cord tissue and in LPS-treated BV2 cells, and its inhibitory effect was comparable to that of Osimertinib. CONCLUSION In rat models of SCI, treatment with Ace can inhibit microglia-mediated inflammatory response by regulating the EGFR/MAPK pathway, thus promoting tissue repair and motor function recovery.
Mice ; Animals ; Rats ; Recovery of Function ; Lipopolysaccharides ; Microglia ; Molecular Docking Simulation ; Spinal Cord Injuries ; Signal Transduction ; Cytokines ; ErbB Receptors

PURPOSE: There are many infectious and inflammatory causes for elevated core-body temperatures, though they rarely pass 40 ℃ (104 ℉). The term "quad fever" is used for extreme hyperpyrexia in the setting of acute cervical spinal cord injuries (SCIs). The traditional methods of treating hyperpyrexia are often ineffective and reported morbidity and mortality rates approach 100%. This study aims to identify the incidence of elevated temperatures in SCIs at our institution and assess the effectiveness of using a non-invasive dry water temperature management system as a treatment modality with mortality. METHODS: A retrospective analysis of acute SCI patients requiring surgical intensive care unit admission who experienced fevers ≥ 40 ℃ (104 ℉) were compared to patients with maximum temperatures < 40 ℃. Patients ≥18 years old who sustained an acute traumatic SCI were included in this study. Patients who expired in the emergency department; had a SCI without radiologic abnormality; had neuropraxia; were admitted to any location other than the surgical intensive care unit; or had positive blood cultures were excluded. SAS 9.4 was used to conduct statistical analysis. RESULTS: Over the 9-year study period, 35 patients were admitted to the surgical intensive care unit with a verified SCI. Seven patients experienced maximum temperatures of ≥ 40 ℃. Six of those patients were treated with the dry water temperature management system with an overall mortality of 57.1% in this subgroup. The mortality rate for the 28 patients who experienced a maximum temperature of ≤ 40 ℃ was 21.4% (p = 0.16). CONCLUSION The diagnosis of quad fever should be considered in patients with cervical SCI in the presence of hyperthermia. In this study, there was no significant difference in mortality between quad fever patients treated with a dry water temperature management system versus SCI patients without quad fever. The early use of a dry water temperature management system appears to decrease the mortality rate of quad fever.
Humans ; Adolescent ; Hyperthermia ; Retrospective Studies ; Cervical Cord ; Spinal Cord Injuries/surgery* ; Neck Injuries ; Soft Tissue Injuries ; Hyperthermia, Induced

Pediatric and adult spinal cord injuries (SCI) are distinct entities. Children and adolescents with SCI must suffer from lifelong disabilities, which is a heavy burden on patients, their families and the society. There are differences in Chinese and foreign literature reports on the incidence, injury mechanism and prognosis of SCI in children and adolescents. In addition to traumatic injuries such as car accidents and falls, the proportion of sports injuries is increasing. The most common sports injury is the backbend during dance practice. Compared with adults, children and adolescents are considered to have a greater potential for neurological improvement. The pathogenesis and treatment of pediatric SCI remains unclear. The mainstream view is that the mechanism of nerve damage in pediatric SCI include flexion, hyperextension, longitudinal distraction and ischemia. We also discuss the advantages and disadvantages of drugs such as methylprednisolone in the treatment of pediatric SCI and the indications and timing of surgery. In addition, the complications of pediatric SCI are also worthy of attention. New imaging techniques such as diffusion tensor imaging and diffusion tensor tractography may be used for diagnosis and assessment of prognosis. This article reviews the epidemiology, pathogenesis, imaging, clinical characteristics, treatment and complications of SCI in children and adolescents. Although current treatment cannot completely restore neurological function, patient quality of life can be enhanced. Continued developments and advances in the research of SCI may eventually provide a cure for children and adolescents with this kind of injury.
Adult ; Child ; Humans ; Adolescent ; Diffusion Tensor Imaging/methods* ; Quality of Life ; Spinal Cord Injuries/therapy* ; Prognosis ; Athletic Injuries ; Spinal Cord/pathology*

PURPOSE: The long-term situation of children with spinal cord injury (SCI) was investigated, and suggestions for helping them better return to the society were provided. METHODS: SCI patients less than 18 years old hospitalized in Beijing Boai Hospital from January 2011 to December 2020 were retrospectively analyzed. Information including motor function, complications, characteristic changes, self-care abilities, school attendance and social participation were collected by telephone interview and electronic questionnaire. All the answers were statistically analyzed. RESULTS: A total of 86 cases were enrolled, 77 girls and 9 boys, with a median injury age of 6 years and 2 months. The follow-up time was 3-130 months. The main cause of trauma in these children was sport injury (66.3%), the thoracic spinal cord was involved the most (91.9%), and complete SCIs accounted for the majority (76.7%). In terms of complications, children with complete SCIs were more likely to have urinary incontinence, constipation and characteristic changes (p < 0.05); whereas the incomplete SCIs often have spasticity (p < 0.05). As to the daily living abilities, children with incomplete lumbar SCIs were more capable to accomplish personal hygiene, transfer, and bathing independently than those with complete injuries, or cervical/thoracic SCIs, respectively (p < 0.05). Moreover, children older than 9 years care more able to dress and transfer independently than the youngers (p < 0.05). Wheelchair users accounted for 84.9% and more than half of them were able to propel wheelchair independently, and those who move passively in wheelchairs were mostly introverted kids (p < 0.05). Almost all (93.8%) children with incomplete injuries were able to walk independently. Most (79.1%) children continued to attending school, and 41.9% participated in interest classes. Unfortunately, 67.4% of the children spent less time playing with their peers than before the injury. CONCLUSION SCIs impair physical structures and function of children, affect their independence in daily living, and restrict school attendance and social interaction. Comprehensive rehabilitation after injury is a systematic work. Medical staff and caregivers should not only pay attention to neurological function, but also help them improve self-care abilities. It is also important to balance rehabilitation training and school work and social participation.
Male ; Female ; Humans ; Child ; Adolescent ; Follow-Up Studies ; Retrospective Studies ; Spinal Cord Injuries/complications* ; Prognosis