Targeting FBN1 and BMP-8: The Potential Mechanism of SDF-1 in Acute Spinal Cord Injury Repair.

Objective To investigate the feasibility of valproic acid (VPA) combined with bone marrow mesenchymal stem cells (BMSCs) to promote restoration of the rat spinal cord injury (SCI) and its mechanism of action. Methods BMSCs from Sprague-Dawley (SD) rats were cultured in vitro. The third generation BMSCs were detected by flow cytometry and collected for use. Spinal cord injury model was Made by modified Allen's techniqtechnique. According to the random number table method sixty adult male SD rats were divided into five groups: control group, SCI model group, VPA treated group, BMSCs transplantation group and VPA combined with MBSCs group. At BMSCs transplantation group and VPA combined with MBSCs group, 1 mL BMSCS, it's concentration is 1×106 /mL, were injected into the spinal cord of injured Segment; while control group, SCI model group and VPA treated group received the same dose of normal saline at the same time point. VPA(300 mg/kg) was administrated in rats through hypodermic injection immediately after injury, then repeated per 12 h until killing; while control group, SCI model group and BMSCs transplantation group received the same dose of normal saline at the same time point. The recovery of the locomotor function of each group was evaluated with basso Basso-beattieBeattie-bresnahan Bresnahan (BBB) scale at 7 d, and 14 d after injury, then the rats were killed. The sections were stained with hematoxylin and eosin (HE) for Syringomyelia area.The expression of Caspase-3 protein was detected with immunohistochemistry. Then the neuronal apoptosis was observed by TUNEL staining. Results (1) By the flow cytometry instrument detection third-generation cultured BMSCs can be stable expressed CD34 and CD44. (2)The motor function of the control group was not affected. The BBB score of the three treatment groups was significantly higher than that of the SCI model group(all P values<0.05). The score of VPA combined with MBSCs group was significantly higher than that of VPA treated group and D on the 14th day after SCI(all P values<0.05). (3)HE staining results showed the area of the lesion area of the four groups were respectively (4.57±0.26), (3. 34±0.21), (3.51±0.18) and (2.43±0.35), respectively. VPA combined with MBSCs group was significantly lower than the other three group(all P values<0.05). (4)Immunohistochemical staining showed that a small amount of Caspase-3 expression was found in control group. The expression of Caspase-3 in three treatment groups was significantly lower than that in SCI model group(P< 0.05). While the expression of Caspase-3 in VPA combined with MBSCs group was significantly lower than that in VPA treated group and D(all P values<0.05). (5)A small number of apoptosis-positive cells were found in control group at 14 days after injury. Compared with SCI model group, the apoptosis index of the three treatment groups was lower(all P values<0.05). The apoptosis index of VPA combined with MBSCs group was significantly lower than that of VPA treated group and BMSCs transplantation group(all P values< 0.05). Conclusions Hypodermic injection of VPA for BMSCs transplantation promote SCI repair in rats is feasible, especially in the lower expression of Caspase-3, inhibition of neural cell apoptosis and promote motor nerve functional recovery effect is remarkable. Key words: Spinal cord injury; Valproic acid; Bone marrow mesenchymal stem cells; Injury repair; Experimental study

A thermosensitive quaternary ammonium chloride chitosan/β-glycerophosphate (HACC/β-GP) hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) transfected with an adenovirus containing the glial cell-derived neurotrophic factor (GDNF) gene (Ad-rGDNF) was applied to spinal cord injury (SCI) repair. The BMSCs from rats were transfected with Ad-rGDNF, resulting in the expression of GDNF mRNA in the BMSCs increasing and their spontaneous differentiation into neural-like cells expressing neural markers such as NF-200 and GFAP. After incubation with HACC/β-GP hydrogel scaffolds for 2 weeks, neuronal differentiation of the BMSCs was confirmed using immunofluorescence (IF), and the expression of GDNF by the BMSCs was detected by Western blot at different time points. MTT assay and scanning electron microscopy confirmed that the HACC scaffold provides a non-cytotoxic microenvironment that supports cell adhesion and growth. Rats with SCI were treated with BMSCs, BMSCs carried by the HACC/β-GP hydrogel (HACC/BMSCs), Ad-rGDNF-BMSCs, or Ad-rGDNF-BMSCs carried by the hydrogel (HACC/GDNF-BMSCs). Animals were sacrificed at 2, 4, and 6weeks of treatment. IF staining and Western blot were performed to detect the expression of NeuN, NF-200, GFAP, CS56, and Bax in the lesion sites of the injured spinal cord. Upon treatment with HACC/BMSCs, NF200 and GFAP were upregulated but CS56 and Bax were downregulated in the SCI lesion site. Furthermore, transplantation of HACC/GDNF-BMSCs into an SCI rat model significantly improved BBB scores and regeneration of the spinal cord. Thus, HACC/β-GP hydrogel scaffolds show promise for functional recovery in spinal cord injury patients.

The principal aim of present study was to assess the therapeutic efficacy of bone morphogenetic protein-7 (BMP-7) induced differentiation of bone marrow mesenchymal stem cells (BMSCs) in a rat acute spinal cord injury (SCI) model. BMSCs were isolated from rats, and then divided into a control and a BMP-7 induction groups. The proliferation ability of BMSCs and glial cell markers were determined. Forty Sprague-Dawley (SD) rats were randomly divided into sham, SCI, BMSC, and BMP7 + BMSC groups (n = 10). Among these rats, the recovery of hind limb motor function, the pathological related markers, and motor evoked potentials (MEP) were identified. BMSCs differentiated into neuron-like cells after the introduction of exogenous BMP-7. Interestingly, the expression levels of MAP-2 and Nestin increased, whereas the expression level of GFAP decreased after the treatment with exogenous BMP-7. Furthermore, the Basso, Beattie, and Bresnahan (BBB) score reached 19.33 ± 0.58 in the BMP-7 + BMSC group at day 42. Nissl bodies in the model group were reduced compared to the sham group. After 42days, in both the BMSC and BMP-7 + BMSC groups, the number of Nissl bodies increased. This is especially so for the number of Nissl bodies in the BMP-7 + BMSC group, which was more than that in the BMSC group. The expression of Tuj-1 and MBP in BMP-7 + BMSC group increased, whereas the expression of GFAP decreased. Moreover, the MEP waveform decreased significantly after surgery. Furthermore, the waveform was wider and the amplitude was higher in BMP-7 + BMSC group than that in BMSC group. BMP-7 promotes BMSC proliferation, induces the differentiation of BMSCsinto neuron-like cells, and inhibits the formation of glial scar. BMP-7 plays a confident role in the recovery of SCI rats.

Addressing spinal cord injury (SCI) through stem cell therapy is currently at the forefront of medical research despite its complexity. In this study, we investigated the potential of the Noggin protein in promoting the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into neuronal cells. We transplanted induced cells into a rat model with spinal cord injury. This exploration proposes an innovative perspective on stem cell therapies for spinal cord injuries. Rat BMSCs were isolated utilizing the bone marrow cell apposition method; The multidirectional differentiation of rat BMSCs was identified by lipid induction and osteogenic induction; Rat BMSCs were induced by different concentrations of Noggin protein and different induction times; Nissel staining was used to identify the induced neuronal-like cells; The expression of synaptic protein Ⅰ (SYN1), glial fibrillary acidic protein (GFAP), and neurofilament protein 200 (NF200) in neuron-like cells was detected by immunofluorescence assay. Rats were randomly divided into a control group and a neuron-like cell group; A rat spinal cord injury model was produced, and neuron-like cells obtained from induction were transplanted into the rat's SCI. The recovery of the rats' hind limbs' motor function was detected by the Basso, Beattie, and Bresnahan (BBB) scores, and the changes in the expression of NF200 mRNA at the spinal cord injury were detected by quantitative real time polymerase chain reaction (qRT-PCR). Our cultured rat BMSCs had a long spindle-shaped morphology and stained positively for oil red O after lipogenic induction and modified alizarin red S after osteogenic induction. Nissel staining of cells obtained from rat BMSCs induced by Noggin protein was positive. Immunofluorescence results showed that the induced neuronal-like cells positively expressed NF200 and SYN1, and negatively expressed GFAP. After local transplantation of induced neuronal-like cells in the rat SCI model, the BBB scores in the neuron-like cell group were higher than those in the control group at 1 w, 2 w, and 4 w, with statistically different results (p < 0.05). According to qRT-PCR results, NF200 at the spinal cord injury in the neuron-like cell group was higher than that in the control group at 12 h, 3 d, 1 w, 2 w, and 4 w, with statistically significant differences in results (p < 0.05). Our findings indicate that Noggin protein effectively facilitates the differentiation of rat BMSCs into neuronal cells, highlighting its potential as a therapeutic agent for repairing spinal cord injuries. This study elucidates a promising avenue in stem cell research, contributing a novel approach to regenerative strategies for spinal cord injuries.

Spinal cord injury (SCI) remains a global challenge due to limited treatment strategies. Transcranial magnetic stimulation (TMS), bone marrow mesenchymal stem cell (BMSC) transplantation and downregulation of Raf/MEK/ERK signaling effectively improve SCI. The combination of BMSCs and TMS displays synergistic effects on vascular dementia. However, whether TMS displays a synergistic effect when combined with BMSC transplantation or Raf inhibitor (RafI) therapy for the treatment of SCI is not completely understood. The present study aimed to compare the therapeutic effect of monotherapy and combination therapy on SCI. In the present study, 8-week-old female Sprague Dawley rats were used to establish a model of SCI using the weight-drop method followed by treatment with monotherapy (TMS, BMSCs or RafI) or combination therapy (TMS+BMSCs or TMS+RafI). The effect of monotherapy and combination therapy on locomotor function, pathological alterations, neuronal apoptosis and expression of axonal regeneration-associated factors and Raf/MEK/ERK signaling-associated proteins in the spinal cord was analyzed by Basso, Beattie and Bresnahan (BBB) scoring, hematoxylin and eosin staining, TUNEL-neuronal nuclei (NeuN) staining and immunofluorescence or western blotting, respectively. The results demonstrated that compared with untreated SCI model rats, monotherapy significantly enhanced locomotor functional recovery, as evidenced by higher BBB scores, and slightly alleviated histopathological lesions of the spinal cord in SCI model rats. Furthermore, monotherapy markedly suppressed neuronal apoptosis and promoted axonal regeneration, as well as inhibiting astroglial activation in SCI model rats. The aforementioned results were demonstrated by significantly decreased numbers of apoptotic neurons, markedly decreased expression levels of glial fibrillary acidic protein (GFAP), significantly increased numbers of NeuN+ cells, markedly increased expression levels of growth-associated protein 43 (GAP-43) and significantly upregulated nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) expression levels in monotherapy groups (excluding the RafI monotherapy group) compared with untreated SCI model rats. In addition, monotherapy markedly suppressed activation of the Raf/MEK/ERK signaling pathway, as evidenced by significantly reduced p-Raf/Raf, p-MEK/MEK and p-ERK/ERK protein expression levels in monotherapy groups (excluding the BMSC monotherapy group) compared with untreated SCI model rats. Notably, combination therapy further alleviated SCI-induced spinal cord lesions and neuronal apoptosis, increased GAP-43, NGF and BDNF expression levels, downregulated GFAP expression levels and inhibited activation of the Raf/MEK/ERK signaling pathway in SCI model rats compared with the corresponding monotherapy groups. Therefore, it was hypothesized that compared with monotherapy, combination therapy displayed an improved therapeutic effect on SCI by further suppressing Raf/MEK/ERK signaling. The results of the present study provided an important basis for the clinical application of combination therapy.

Neurogenic Lower Urinary Tract Dysfunction in the First Year After Spinal Cord Injury: A Descriptive Study of Urodynamic Findings.

Translational Advances in the Management of Acute Spinal Cord Injury

Background: Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system, and there is currently no effective treatment for SCI because of its complicated pathophysiology. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation abilities. Our study aims to explore the effects of bone morphogenetic protein 7 (BMP-7)-modified BMSCs transplantation on the repair of SCI in rats. Methods: In this study, a rat spinal cord injury model was established with the modified Allen method. Then, BMSCs transfected with the BMP7 gene were transplanted to treat the spinal cord injury in rats. Forty Sprague-Dawley rats were randomly divided into the sham operation group (sham group), spinal cord injury group (model group), BMSC treatment group (BMSC group) and LV-BMP7-BMSC treatment group (LV-BMP7-BMSC group). The Basso, Beattie, and Bresnahan (BBB) score was used to evaluate the recovery of hindlimb function in the rats. The levels of neurofilament protein NF-200 (NF-200) and glial fibrillary acidic protein (GFAP) were detected by immunofluorescence, RT-PCR and Western blotting. Results: At 14 d, 21 d, and 28 d after treatment, the BBB score of the rats in the LV-BMP7-BMSC group was higher than that of the rats in the model group and BMSC group. The results showed that NF-200 was expressed at the local spinal cord injury site. Compared with that of the sham group, the NF-200 expression level of the BMSC group and LV-BMP7-BMSC group was increased (P < 0.05). The results showed that the mRNA expression levels of NF-200 in the spinal cord tissue of the BMSC group and LV-BMP7-BMSC group were increased compared with those of the sham group (P < 0.05). The western blotting results further confirmed the PCR results. Conclusion: BMP-7 gene-modified BMSC transplantation can promote the repair of spinal cord functions after SCI in rats.

Bone marrow mesenchymal stem cells (BMSCs) on the repair of spinal cord injury (SCI) in rats as well as the role of transforming growth factor-β (TGF-β)/Smads signaling pathway in the repair were investigated. Rat BMSCs and astrocyte-spinal cords (ASCs) were isolated and cultured in vitro, and the cell purity was detected by flow cytometry. ASCs were co-cultured with TGF-β1, BMSCs and BMSCs + TGF-β1, respectively, and grouped accordingly, and ASCs cultured conventionally were included into control group. 3-(4,5)-Dimethylthiahiazo(-z-y1)-3,5-diphenyltetrazoliumbromide (MTT) assay was conducted to detect the proliferation ability of ASCs in each group. Western blotting (WB) was utilized to examine the expression of TGF-β/Smads signaling pathway-related proteins [TGF-β1, Smad2 and phosphorylated (p)-Smad2] in ASCs and ASCs co-cultured with BMSCs. A rat model of SCI was established, and BMSCs were injected locally. Then (BBB) score was used to evaluate spinal cord repair, and WB was adopted to detect the expression of TGF-β1, Smad2 and p-Smad2 at the injured site. BMSCs and ASCs isolated in vitro grew well. According to MTT assay results, TGF-β1 significantly promoted the proliferation of ASCs (P<0.05), and co-culture of ASCs and BMSCs remarkably reduced the proliferation of ASCs (P<0.05). The detection of protein expression at the SCI site via WB demonstrated that the expression of TGF-β1, Smad2 and p-Smad2 in SCI group were obviously upregulated compared with those in Sham group at 1 week (P<0.05), and the injection of BMSCs could markedly downregulate the expression (P<0.05). After 3 week, there were no significant differences in the expression of TGF-β1, Smad2 and p-Smad2 among groups (P>0.05). The transplantation of BMSCs can improve the spinal function of SCI rats probably by inhibiting the TGF-β/Smads signaling pathway and reducing the proliferation of ASCs.

Transplantation of bone marrow mesenchymal stem cells (BMSCs) represents an encouraging strategy for the repair of spinal cord injury (SCI), however, its effectiveness on treating SCI remains controversial. Bilobalide isolated from Ginkgo biloba leaves shows significant neuroprotective effects. We examined the role and underlying mechanism of bilobalide in the efficacy of BMSC transplantation on SCI. Primary BMSCs were isolated from neonatal rats, and cell viability was assessed by MTT assay. Neuronal markers (MAP-2, NeuN, NSE and Tuj1), autophagy markers (LC3 and Beclin1), and Fragile X mental retardation protein (FMRP)/With-no-lysine kinase-1 (WNK1) signaling were measured using RT-qPCR and western blotting. The relationship of FMRP and WNK1 was estimated by RNA immunoprecipitation, while WNK1 mRNA stability was assessed with actinomycin D assay. In a SCI rat model, tissue injury was examined using HE and Nissl staining. Bilobalide treatment facilitated neural differentiation of BMSCs, as well as enhanced autophagy and inhibited WNK1 signaling. The promotive effect of bilobalide on BMSC differentiation was antagonized when overexpressing WNK1 or inhibiting autophagy. Bilobalide upregulated FMRP to promote WNK1 mRNA decay, thus reducing WNK1 expression. FMRP knockdown reversed the promoted functions of bilobalide on autophagy and neuronal differentiation in BMSCs. Additionally, compared to either monotherapy, simultaneous treatments with bilobalide and BMSCs further facilitated autophagy and neuronal differentiation, thereby enhancing the repair of SCI in rats. Bilobalide enhances autophagy activity to promote BMSC neuronal differentiation via FMRP/WNK1 axis, thus improving functional recovery following SCI, which indicates a promising therapeutic approach for SCI.

Preclinical experimental study. To explore the use of hydrogels as bioactive scaffolds for encapsulating bone marrow mesenchymal stem cells (BMSCs) to enhance their therapeutic potential in spinal cord injury (SCI). This study further aims to evaluate the added value of a BMP7 nanoparticle delivery system in overcoming the limitations of BMSCs alone for SCI repair. SCI leads to significant neuron loss and functional impairment. Although BMSC-based stem cell therapies show promise, their efficacy is limited by challenges such as the instability of bone morphogenetic protein (BMP)-7 in inducing neuronal differentiation. High concentrations of BMP7, although effective in promoting neuronal differentiation, may cause inflammation, necessitating the development of a delivery system for sustained and localized release. BMSCs were isolated from Sprague-Dawley rats, and BMP-7's effects on neuronal differentiation were assessed through western blotting. BMP7-loaded nanoparticles (NPs) and BMSCs were co-loaded into a gelatin methacrylate (Gel-MA) hydrogel scaffold, with a cell loading density of 1 × 10 5 cells/μl. BMP7 was encapsulated at a 0.04% (w/V) concentration, corresponding to approximately 0.4ng BMP7 per μl of hydrogel. Optimization was performed using mechanical, cytotoxicity, and neuronal marker analyses. Scaffold properties, including water absorption, BMP7 release, and BMSC morphology, were characterized. Therapeutic efficacy was evaluated in a rat SCI model using motor function recovery, histologic analysis, and molecular assessments. BMP-7 effectively promoted BMSC differentiation into neurons while suppressing glial cell development. The BMP7-NPs/Gel-MA scaffold ensured sustained BMP7 release, achieving optimal differentiation at a 0.04% (w/V) BMP7 concentration. In vivo , the scaffold combined with BMSCs enhanced neuronal proliferation and differentiation, stimulated myelin regeneration, reduced lesion volume, and significantly improved motor function recovery. The BMP7-NPs/Gel-MA scaffold provides sustained delivery of BMP-7, effectively directing BMSC differentiation into neuron-like cells while avoiding glial commitment. Combined with BMSCs, it offers a promising therapeutic strategy for SCI repair.

We transplanted RADA16-PRG self-assembled nanopeptide scaffolds (SAPNSs), bone mesenchymal stem cells (BMSCs), and a brain-derived neurotrophic factor (BDNF)-expressing adeno-associated virus (AAV) into rats subjected to acute spinal cord injury (SCI) to investigate the effects of these transplantations on acute SCI repair and explore their mechanisms. Forty-eight SCI rats were randomly divided into four groups: BBR, BR, B, and NC groups. Seven and 28 days after SCI, evoked potentials (EPs) and BBB scores were assessed to evaluate the recovery of rats' motor behavior and sensory function after injury. HE and toluidine blue staining were performed to investigate the histological structure of the spinal cord tissue of rats from each group, and immunofluorescence staining was used to observe the red fluorescent protein (RFP) intensity of BMSCs and glial fibrillary acidic protein (GFAP) and neurofilament (NF) in the damaged area in each group. RT-PCR was utilized to detect the expression levels of the BDNF, GFAP, and neuron-specific enolase (NSE) genes in the injured area in each group. The results showed that cotransplantation of RADA16-PRG-SAPNs, BMSCs, and BDNF-AVV promoted the spinal cord's motor and sensory function of SCI rats; increased levels of BMSCs, inhabited glial cells proliferation, and promoted neurons proliferations in the injured area; and increased NF, BDNF, and NSE levels and decreased its GFAP in the injured area. Thus, cotransplantation of RADA16-PRG-SAPNS, BMSCs, and BDNF-AAV can prolong the survival time of BMSCs in rats, reduce the postoperative scarring caused by glial proliferation, and promote the migration and proliferation of neurons in the injured area, resulting in the promotion of functional repair after acute SCI.

Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321. From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0-60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI -1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group. NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies. EU program Horizon2020; Swiss State Secretariat for Education, Research and Innovation; Wings for Life; the Swiss Paraplegic Foundation; and the CeNeReg project of Wyss Zurich (University of Zurich and Eidgenössische Technische Hochschule Zurich).

To define the occurrence rate, time course, and potential etiologic factors of hyponatremia in patients with acute spinal cord injury. Analysis of data obtained from a retrospective review of medical records and from a systematized, prospective database pertaining to patients with spinal cord injury. A university hospital with a federally funded regional spinal cord injury center and a dedicated spinal cord injury intensive care unit. Two hundred eighty-two patients admitted between January 1, 1988 and December 31, 1989 with acute (< 24-hr duration) spinal cord or vertebral column injury. None. The mean age of patients was 36.7 +/- 17.6 (SD) yrs; 225 (80%) of the patients were male and 57 (20%) were female. Hyponatremia, when it occurred, developed at a mean time of 6.4 +/- 6.7 days postadmission, reached its nadir at 8.7 +/- 8.8 days, and occurred in 28% of those patients with cervical injuries, 34% with thoracic injuries, and 27% with lumbar injuries (p = NS). Logistic regression analysis demonstrated that the type of spinal cord injury (Frankel class: range is A = complete neurologic lesion to E = no neurologic lesion) was the strongest predictor of hyponatremia. The occurrence rate of hyponatremia was as follows: Frankel class-A 62%; Frankel class-B 48%; Frankel class-C 41%; Frankel class-D 23%; Frankel class-E 16% (p < .0001). The prevalence of hyponatremia in acute spinal cord injury is much higher than in the general medical or surgical patient population. This abnormality usually occurs within the first week postinjury. The most significant predictor of hyponatremia is the type rather than the level of spinal cord injury. The potential etiological factors are many and these factors are probably interrelated. The pathophysiological mechanisms that result in hyponatremia must be explored so that this occurrence and its consequences can be prevented.

Background: The optimal time to rescue spinal cord function after spinal cord injury is within 24 hours, especially within 3 to 8 hours, after the injury. Timely and proper pre-hospital first aid, hospital admission, patient assessment, and surgery are essential for the rescue of spinal cord function. A sound and rapid treatment system is the basis for improving the level of injury treatment and recovery of spinal cord function. China currently lacks a systematic and standardized treatment system. Methods/Design: We herein propose our study protocol for a prospective, multicenter, nonrandomized controlled trial. We will recruit 200 patients with acute spinal cord injury undergoing pre-hospital treatment at Beijing Emergency Medical Center and Beijing Red Cross Emergency Rescue Center and receiving in-hospital treatment at Peking University People's Hospital, Peking University Third Hospital, Beijing Friendship Hospital Affiliated to Capital Medical University, Chaoyang Hospital Affiliated to Capital Medical University, and Chinese PLA General Hospital, China. This study will comprise two parts: (1) establishment of a database of patients with spinal cord injury in the Beijing area; and (2) formulation of the pre-hospital and in-hospital process and establishment of a standardized treatment protocol for acute spinal cord injury. The primary outcome will be the American Spinal Injury Association impairment scale score for spinal nerve function. The secondary outcomes will be spinal X-ray, three-dimensional computed tomography, and magnetic resonance imaging findings and the incidence of complications due to improper pre-hospital and in-hospital treatment of acute spinal cord injury. Discussion: The aims of this study are as follows: (1) We will establish a spine and spinal cord injury treatment database in the Beijing area. (2) We will assess the complete pre-hospital and in-hospital evaluation of spine and spinal cord injury, develop and optimize first aid procedures, and create a pre-hospital and in-hospital standardized training program for the treatment of spine and spinal cord injury. (3) We will build a pre-hospital and in-hospital first aid “green channel” for acute spine and spinal cord injury after completion of the study. (4) We will develop first aid guidelines and establish an evaluation and treatment system for early surgery to save spinal cord function and reduce the degree of disability to the greatest extent as possible. (5) We anticipate that our results will be used in expert consensuses on acute spinal cord injury and that “green channel” patterns will be promoted in hospitals in Beijing and other cities of China to improve the level of first aid treatment of acute spine and spinal cord injury in Chinese cities and reduce the occurrence of secondary injury and severe dysfunction due to improper treatment. This trial will begin in May 2017. Patient recruitment will be finished in August 2019. Analysis of all data and results will be completed in December 2020. Trial registration: ClinicalTrials.gov identifier: NCT03103516. Ethics: All protocols will be in accordance with Ethical Principles for Medical Research Involving Human Subjects in the Declaration of Helsinki (2013), formulated by the World Medical Association. The study protocol has been approved by the Medical Ethics Committee of Peking University People's Hospital, China (approval number: 2016PHB136-01). Informed consent: Written informed consent will be provided by legal representative of participants.