A Novel Method of Making Hinges Using a Newly Designed Sharp Rongeur to Enhance Radiological and Clinical Outcomes in French-Door Cervical Expansive Laminoplasty.

OBJECTIVE: Although the lamina open angle of making hinges is closely related to the outcomes of French-door laminoplasty (FDL) for treatment of cervical spondylosis, there have been no methods to predict the lamina open angle preoperatively as yet. The aim of this study was to investigate the accuracy of predicting the laminal open angle using our newly designed sharp rongeur, and to compare the postoperative outcomes and complications between the methods of making hinges using the newly designed sharp rongeur and the traditional high-speed micro-drill during the FDL. METHODS: This was a single-center retrospective study. Following the approval of the institutional ethics committee, a total of 39 patients (Male: 28; Female: 11) diagnosed with cervical spondylos who underwent FDL in our institution between January 2018 and May 2019 were enrolled. Patients were divided into two groups based on the method of making hinges (sharp rongeur: 22 cases; high-speed micro-drill: 17 cases). The average age at surgery was 59.1 years (range: 16-85 years). The radiological parameters, clinical outcomes, modified Japanese Orthopaedic Association (mJOA) scale score, and the recovery rate of mJOA were recorded and compared between the groups, respectively. The radiological parameters and clinical measurements at pre- and post-operation stages were compared using the paired-sample t-test, the Wilcoxon signed-rank test, and the Friedman's test, and variables in the two groups were analyzed using an unpaired Student's t-test or a Mann-Whitney U test. RESULTS: The average follow-up period was 20.4 months (range: 14.0-25.9 months), the postoperative open angle was 60.13° ± 3.69° in the rongeur group with 22.78° ± 4.34° of angular enlargement, which was significantly lower than that of 68.96° ± 1.00° in the micro-drill group with 32.75° ± 4.22° of angular enlargement (U = 19.000, p < 0.001). The rongeur group showed a higher fusion rate (34.1% vs 14.7%, χ2  = 11.340, p = 0.001), and a lower fracture rate of the lamina (7.8% vs 25.5%, χ2  = 14.185, p < 0.001) at 1-month post-surgery, compared to the micro-drill group. There were no significant differences in the clinical outcomes and postoperative complications between the two groups (p > 0.05), except in the recovery rate of mJOA scores (0.836 ± 0.138 vs 0.724 ± 0.180, U = 115.000, p = 0.042) and neck disability index (NDI) at the final follow-up (7.55 ± 10.65 vs 14.71 ± 8.72, U = 94.000, p = 0.008). CONCLUSIONS: The special sharp rongeur with a tip angle of 20° could be a preferred method to make hinges during FDL, which can predict the laminal open angle accurately and enlarge it to about 23°, thus reducing the fracture rate and accelerating the bony fusion of hinges compared with the outcomes of the traditional micro-drill method.

Neoepitope fragments as biomarkers for different phenotypes of intervertebral disc degeneration.

Background: During the intervertebral disc (IVD) degeneration process, initial degenerative events occur at the extracellular matrix level, with the appearance of neoepitope peptides formed by the cleavage of aggrecan and collagen. This study aims to elucidate the spatial and temporal alterations of aggrecan and collagen neoepitope level during IVD degeneration. Methods: Bovine caudal IVDs were cultured under four different conditions to mimic different degenerative situations. Samples cultured after 1- or 8-days were collected for analysis. Human IVD samples were obtained from patients diagnosed with lumbar disc herniation (LDH) or adolescent idiopathic scoliosis (AIS). After immunohistochemical (IHC) staining of Aggrecanase Cleaved C-terminus Aggrecan Neoepitope (NB100), MMP Cleaved C-terminus Aggrecan Neoepitope (MMPCC), Collagen Type 1α1 1/4 fragment (C1α1) and Collagenase Cleaved Type I and II Collagen Neoepitope (C1,2C), staining optical density (OD)/area in extracellular matrix (OECM) and pericellular zone (OPCZ) were analyzed. Conditioned media of the bovine IVD was collected to measure protein level of inflammatory cytokines and C1,2C. Results: For the bovine IVD sections, the aggrecan MMPCC neoepitope was accumulated in nucleus pulposus (NP) and cartilage endplate (EP) regions following mechanical overload in the one strike model after long-term culture; as for the TNF-α induced degeneration, the OECM and OPCZ of collagen C1,2C neoepitope was significantly increased in the outer AF region after long-term culture; moreover, the C1,2C was only detected in conditioned medium from TNF-α injection + Degenerative loading group after 8 days of culture. LDH patients showed higher MMPCC OECM in NP and higher C1,2C OECM in AF region compared with AIS patients. Conclusions: In summary, aggrecan and collagen neoepitope profiles showed degeneration induction trigger- and region-specific differences in the IVD organ culture models. Different IVD degeneration types are correlated with specific neoepitope expression profiles. These neoepitopes may be helpful as biomarkers of ECM degradation in early IVD degeneration and indicators of different degeneration phenotypes.

Toward the Next Generation of Spine Bioreactors: Validation of an Ex Vivo Intervertebral Disc Organ Model and Customized Specimen Holder for Multiaxial Loading.

A new generation of bioreactors with integrated six degrees of freedom (6 DOF) aims to mimic more accurately the natural intervertebral disc (IVD) load. We developed and validated in a biological and mechanical study a specimen holder and corresponding ex vivo IVD organ model according to the bioreactor requirements for multiaxial loading and a long-term IVD culture. IVD height changes and cell viability were compared between the 6 DOF model and the standard 1 DOF model throughout the 3 weeks of cyclic compressive loading in the uniaxial bioreactor. Furthermore, the 6 DOF model and holder were loaded for 9 days in the multiaxial bioreactor under development using the same conditions, and the IVDs were evaluated for cell viability. The interface of the IVD model and specimen holder, enhanced with fixation screws onto the bone, was tested in compression, torsion, lateral bending, and tension. Additionally, critical motions such as tension and bending were assessed for a combination of side screws and top screws or side screws and adhesive. The 6 DOF model loaded in the uniaxial bioreactor maintained similar cell viability in the IVD regions as the 1 DOF model. The viability was high after 2 weeks throughout the whole IVD and reduced by more than 30% in the inner annulus fibrous after 3 weeks. Similarly, the IVDs remained highly viabile when cultured in the multiaxial bioreactor. In both models, IVD height changes after loading were in the range of typical physiological conditions. When differently directed motions were applied, the holder-IVD interface remained stable under hyper-physiological loading levels using a side screw approach in compression and torsion and the combination of side and top screws in tension and bending. We thus conclude that the developed holding system is mechanically reliable and biologically compatible for application in a new generation of multiaxial bioreactors.

Transcriptional profiling of intervertebral disc in a post-traumatic early degeneration organ culture model.

INTRODUCTION: The goal of this study is to characterize transcriptome changes and gene regulation networks in an organ culture system that mimics early post-traumatic intervertebral disc (IVD) degeneration. METHODS: To mimic a traumatic insult, bovine caudal IVDs underwent one strike loading. The control group was cultured under physiological loading. At 24 hours after one strike or physiological loading, RNA was extracted from nucleus pulposus (NP) and annulus fibrosus (AF) tissue. High throughput next generation RNA sequencing was performed to identify differentially expressed genes (DEGs) between the one strike loading group and the control group. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes analyses were performed to analyze DEGs and pathways. Protein-protein interaction (PPI) network was analyzed with cytoscape software. DEGs were verified using qRT-PCR. Degenerated human IVD tissue was collected for immunofluorescence staining to verify the expression of DEGs in human disc tissue. RESULTS: One strike loading resulted in significant gene expression changes compared with physiological loading. In total 253 DEGs were found in NP tissue and 208 DEGs in AF tissue. Many of the highly dysregulated genes have known functions in disc degeneration and extracellular matrix (ECM) homeostasis. ACTB, ACTG, PFN1, MYL12B in NP tissue and FGF1, SPP1 in AF tissue were verified by qRT-PCR and immunofluorescence imaging. The identified DEGs were involved in focal adhesion, ECM-receptor interaction, PI3K-AKT, and cytokine-cytokine receptor interaction pathways. Three clusters of PPI networks were identified. GO enrichment revealed that these DEGs were mainly involved in inflammatory response, the ECM and growth factor signaling and protein folding biological process. CONCLUSION: Our study revealed different DEGs, pathways, biological process and PPI networks involved in post-traumatic IVD degeneration. These findings will advance the understanding of the pathogenesis of IVD degeneration, and help to identify novel biomarkers for the disease diagnosis.

Noninvasive multimodal fluorescence and magnetic resonance imaging of whole-organ intervertebral discs.

Low back pain (LBP) is a commonly experienced symptom posing a tremendous healthcare burden to individuals and society at large. The LBP pathology is strongly linked to degeneration of the intervertebral disc (IVD), calling for development of early-stage diagnostic tools for visualizing biomolecular changes in IVD. Multimodal measurements of fluorescence molecular tomography (FMT) and magnetic resonance imaging (MRI) were performed on IVD whole organ culture model using an in-house built FMT system and a high-field MRI scanner. The resulted multimodal images were systematically validated through epifluorescence imaging of the IVD sections at a microscopic level. Multiple image contrasts were exploited, including fluorescence distribution, anatomical map associated with T1-weighted MRI contrast, and water content related with T2 relaxation time. The developed multimodality imaging approach may thus serve as a new assessment tool for early diagnosis of IVD degeneration and longitudinal monitoring of IVD organ culture status using fluorescence markers.

Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury.

STAT3 is expressed in neural stem cells (NSCs), where a number of studies have previously shown that STAT3 is involved in regulating NSC differentiation. However, the possible molecular mechanism and role of STAT3 in spinal cord injury (SCI) remain unclear. In the present study, the potential effect of STAT3 in NSCs was first investigated by using short hairpin RNA (shRNA)-mediated STAT3 knockdown in rat NSCs in vitro. Immunofluorescence of ß3-tubulin and glial fibrillary acidic protein staining and western blotting showed that knocking down STAT3 expression promoted NSC neuronal differentiation, where the activity of mTOR was upregulated. Subsequently, rats underwent laminectomy and complete spinal cord transection followed by transplantation of NSCs transfected with control-shRNA or STAT3-shRNA at the injured site in vivo. Spinal cord-evoked potentials and the Basso-Beattie-Bresnahan scores were used to examine functional recovery. In addition, axonal regeneration and tissue repair were assessed using retrograde tracing with FluoroGold, hematoxylin and eosin, Nissl and immunofluorescence staining of ß3-tubulin, glial fibrillary acidic protein and microtubule-associated protein 2 following SCI. The results showed that transplantation with NSCs transfected with STAT3-RNA enhanced functional recovery following SCI and promoted tissue repair in rats, in addition to improving neuronal differentiation of the transplanted NSCs in the injury site. Taken together, in vitro and in vivo evidence that inhibiting STAT3 could promote NSC neuronal differentiation was demonstrated in the present study. Therefore, transplantation with NSCs with STAT3 expression knocked down appears to hold promising potential for enhancing the benefit of NSC-mediated regenerative cell therapy for SCI.

Analysis of Cervical Spine Alignment Change after Modified Kurokawa Cervical Laminoplasty in the Patients with Cervical Myelopathy and Straight Cervical Spine.

Laminoplasty is widely used to decompress the spinal cord in patients with multilevel cervical lesions. Straight cervical alignment may not be a good candidate for laminoplasty because of postoperation progression of kyphosis and loss of cervical spine range of motion (ROM). However, clinical outcomes of laminoplasty did not show a strong and consistent effect based on cervical sagittal alignment. Moreover, the kyphosis progression and ROM change after operation for the patients with preoperative strange cervical alignment are still unclear. This study is to evaluate the change of cervical alignment and ROM in patients with straight cervical alignment after modified Kurokawa cervical laminoplasty. Thirty patients with multiple-level cervical spondylosis (CSM) and straight cervical alignment were included. All patients underwent laminoplasty with the reconstruction of the spinous process-ligament-muscular complex (SPLMC). The modified JOA score was analyzed for clinical assessment. The change of cervical alignment, ROM, T1 slope, and intervertebral disc space Cobb angle were analyzed for radiological assessment. The average JOA score at preoperative and 2 years follow-up were 7.8 ± 1.4 and 13.6 ± 2.1, respectively. The recovery ratio was 63%. At the 2 years follow-up, there were 18 patients who acquired lordotic cervical alignment. 10 patients remained as straight cervical curve, and 2 patients' cervical alignment developed mild kyphosis. 28 out of 30 patients showed improvement of cervical alignment. The cervical alignment was improved from 1.29 ± 10.04° preoperative to 9.58 ± 8.65° postoperative. However, the ROM decreased from 36.8 ± 18.92 preoperative to 25.08 ± 12.10° postoperative. A positive correlation was found between the C2/4 angle change and cervical alignment change, T1 slope and cervical alignment, cervical alignment, and neutral position flexion reserved ROM. A negative correlation was found between the C1/2 angle change and cervical alignment change. Laminoplasty with a reconstruction of SPLMC followed by appropriate postoperative muscle exercises may be an encouraging way to maintain or improve physiological alignment and prevent postoperation kyphosis deformity at 2 years follow-up.

One strike loading organ culture model to investigate the post-traumatic disc degenerative condition.

BACKGROUND: Acute trauma on intervertebral discs (IVDs) is thought to be one of the risk factors for IVD degeneration. The pathophysiology of IVD degeneration induced by single high impact mechanical injury is not very well understood. The aim of this study was using a post-traumatic IVD model in a whole organ culture system to analyze the biological and biomechanical consequences of the single high-impact loading event on the cultured IVDs. METHODS: Isolated healthy bovine IVDs were loaded with a physiological loading protocol in the control group or with injurious loading (compression at 50% of IVD height) in the one strike loading (OSL) group. After another 1 day (short term) or 8 days (long term) of whole organ culture within a bioreactor, the samples were collected to analyze the cell viability, histological morphology and gene expression. The conditioned medium was collected daily to analyze the release of glycosaminoglycan (GAG) and nitric oxide (NO). RESULTS: The OSL IVD injury group showed signs of early degeneration including reduction of dynamic compressive stiffness, annulus fibrosus (AF) fissures and extracellular matrix degradation. Compared to the control group, the OSL model group showed more severe cell death (P â€‹< â€‹0.01) and higher GAG release in the culture medium (P â€‹< â€‹0.05). The MMP and ADAMTS families were up-regulated in both nucleus pulposus (NP) and AF tissues from the OSL model group (P â€‹< â€‹0.05). The OSL injury model induced a traumatic degenerative cascade in the whole organ cultured IVD. CONCLUSIONS: The present study shows a single hyperphysiological mechanical compression applied to healthy bovine IVDs caused significant drop of cell viability, altered the mRNA expression in the IVD, and increased ECM degradation. The OSL IVD model could provide new insights into the mechanism of mechanical injury induced early IVD degeneration. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This model has a high potential for investigation of the degeneration mechanism in post-traumatic IVD disease, identification of novel biomarkers and therapeutic targets, as well as screening of treatment therapies.

Small molecule-based treatment approaches for intervertebral disc degeneration: Current options and future directions.

Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent in vitro, in vivo, and pre-clinical studies.

Identification and Characterization of Serum microRNAs as Biomarkers for Human Disc Degeneration: An RNA Sequencing Analysis.

Circulating microRNAs (miRNAs) have been associated with various degenerative diseases, including intervertebral disc (IVD) degeneration. Lumbar disc herniation (LDH) often occurs in young patients, although the underlying mechanisms are poorly understood. The aim of this work was to generate RNA deep sequencing data of peripheral blood samples from patients suffering from LDH, identify circulating miRNAs, and analyze them using bioinformatics applications. Serum was collected from 10 patients with LDH (Disc Degeneration Group); 10 patients without LDH served as the Control Group. RNA sequencing analysis identified 73 differential circulating miRNAs (p < 0.05) between the Disc Degeneration Group and Control Group. Gene ontology enrichment analysis (p < 0.05) showed that these differentially expressed miRNAs were associated with extracellular matrix, damage reactions, inflammatory reactions, and regulation of apoptosis. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes were involved in diverse signaling pathways. The profile of miR-766-3p, miR-6749-3p, and miR-4632-5p serum miRNAs was significantly enriched (p < 0.05) in multiple pathways associated with IVD degeneration. miR-766-3p, miR-6749-3p, and miR-4632-5p signature from serum may serve as a noninvasive diagnostic biomarker for LHD manifestation of IVD degeneration. Furthermore, several dysregulated miRNAs may be involved in the pathogenesis of IVD degeneration. Further study is needed to confirm the functional role of the identified miRNAs.

The Optimal Timing of Hydrogel Injection for Treatment of Intervertebral Disc Degeneration: Quantitative Analysis Based on T1ρ MR Imaging.

STUDY DESIGN: Animal experimental study. OBJECTIVE: The aim of this study was to investigate the optimal time of hydrogel injection for regenerating intervertebral disc degeneration (IDD) based on T1ρ magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: Currently, different approaches are being pursued to regenerate the IDD. However, the optimal timing for the regenerative intervention is unclear. METHODS: The slowly, progressive IDD models were established in 18 rhesus monkeys. On the basis of the MR T1ρ values of the discs, the rhesus monkeys were divided into severe (T1ρ values: <81 ms), moderate (T1ρ values: 81∼95 ms), and mild (T1ρ values: 96∼110 ms) degeneration groups. Biocompatible hydrogel was injected into the central part of the nucleus pulposus of the discs under fluoroscopic guidance. Treatment effects were investigated using radiography, T1ρ MRI, and histology until 12 months postoperatively. RESULTS: After injection, the T1ρ values of all the discs increased significantly at 1 month postoperatively, and then remained at approximately 110 ms in the mild and moderate groups during the whole observation period, with no significant difference compared to the values at 1 month (P > 0.05). However, in the severe group, the T1ρ values decreased significantly after 1 month and leveled at approximately 70 ms after 6 months, with significant difference compared to the values at 1 month (P < 0.05). In the mild and moderate groups, there were no significant differences between preoperative histological scores and those at 12 months (P > 0.05). However, the histological score in the severe group at 12 months was significantly higher than the preoperative scores (P < 0.05). CONCLUSION: This study suggested that the moderate degenerative stage of IDD (T1ρ values from 95 to 80 ms) could be the optimal time for hydrogel injection aimed at the regenerative intervention, based on T1ρ-MR imaging technique and quantitative analysis. LEVEL OF EVIDENCE: N/A.

Analysis of the morphometric change in the uncinate process of the cervical spondylosis patients: A study of radiological anatomy.

PURPOSE: Although there are many researches that focus on the relationship between the vertebral artery and uncinate process (UP), there were no publications concerning difference in the dimensions of the UP between the normal spine and degenerative spine, especially in Chinese patient. The purpose of this study is to determine the anatomic parameters that can be used as a guide for the procedure in intervertebral foramen decompression and for analysis of the morphometric change in the UP of the cervical spondylosis patients. METHODS: Forty patients from January 2016 to January 2019 were enrolled in this study. Three-dimensional computed tomography scans of the cervical spine were performed. The patients were subdivided into two groups which were nondegenerative cervical spine group (20 cases) and degenerative cervical spine group (20 cases). Six parameters concerning the height, width and angle of the UP were measured. RESULTS: In nondegenerative group, the average pedicle width was 3.63 mm-5.91 mm from C3 to C7. The average width of safe UP resection will be 3.06 mm at C3, 3.12 mm at C4, 3.28 mm at C5, 2.74 mm at C6 and 2.01 mm at C7. The average safe depth will be 6.04 mm at C3, 6.52 mm at C4, 7.61 mm at C5, 6.07 mm at C6 and 5.09 mm at C7. There are statistic difference between degenerative group and nondegenerative group, especially in the parameter minimum height of UP, maximum height of UP, medial border's distance of UP and later border's distance of UP. CONCLUSION: In this retrospective study, our results suggest that for the Chinese patients who suffered from cervical spondylosis could be performed intervertebral foraminotomy decompression by resecting part of the UP. The safe range within the spinal canal was up to 6.73 mm of width between inferior vertebral endplate and superior vertebral endplate in the intervertebral space and up to 5.09 mm of depth from medial border of the UP to the lateral side atC3 to C7 without interfering the spinal nerve root and vertebral artery. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study found the safe margin to perform intervertebral foramen decompression to the UP for the cervical spondylosis patients. This may help to improve safeness of the surgical procedure and provide data for future robotic surgery.

Mechanical and biological characterization of a composite annulus fibrosus repair strategy in an endplate delamination model.

This study compares the mechanical response of the commonly used annulus fibrosus (AF) puncture injury model of the intervertebral disc (IVD) and a newly proposed AF failure at the endplate junction (delamination) on ex vivo bovine IVDs. Biocompatibility and mechanics of a newly developed repair strategy comprising of electrospun polycaprolactone (PCL) scaffold and fibrin-genipin (FibGen) adhesive was tested on the delamination model. The study found no significant difference in the mechanical response to compressive loading between the two models. Primary goals of the repair strategy to create a tight seal on the damage area and restore mechanical properties, while showing minimal cytotoxicity, were broadly achieved. Postrepair, the IVDs showed a significant restoration of mechanical properties compared to the injured samples for the delamination model. The FibGen glue showed a limited toxicity in the AF and produced a resilient and mechanically stable seal on the damaged area.

Intervertebral disc organ culture for the investigation of disc pathology and regeneration - benefits, limitations, and future directions of bioreactors.

Low back pain is the leading cause of disability worldwide and in many patients the source of pain can be attributed to pathological changes within the intervertebral disc (IVD). As present treatment options fail to address the underlying biological problem, novel therapies are currently subject to intense research. The physiologic IVD microenvironment features a highly complex interaction of biochemical and mechanical factors influencing cell metabolism and extracellular matrix turnover and is therefore difficult to simulate for research purposes on IVD pathology. The first whole organ culture models were not able to sufficiently replicate human in vivo conditions as mechanical loading, the predominant way of IVD nutrient supply and waste exchange, remained disregarded. To mimic the unique IVD niche more realistically, whole organ culture bioreactors have been developed, allowing for dynamic loading of IVDs and nutrient exchange. Recent advancements on bioreactor systems have facilitated whole organ culture of various IVDs for extended periods. IVD organ culture bioreactors have the potential to bridge the gap between in vitro and in vivo systems and thus may give valuable insights on IVD pathology and/or potential novel treatment approaches if the respective model is adjusted according to a well-defined research question. In this review, we outline the potential of currently utilized IVD bioreactor systems and present suggestions for further developments to more reliably investigate IVD biology and novel treatment approaches.

Successful surgery for a neuromuscular scoliosis patient by pulmonary rehabilitation with forced vital capacity below 30.

A rare case of a 15-year-old male patient with neuromuscular scoliosis with forced vital capacity (FVC) below 30%, who went through a successful surgery without any pulmonary complications, is reported herein. The patient had obvious asymmetric shoulders and poor exercise tolerance. The Cobb's angle of the main thoracic curve was 62.8°, and FVC in sitting position was 18% of predictive value. After skull traction and pulmonary rehabilitation, the FVC was still below 30%, and he finally went through surgery under this serious condition. By early pulmonary rehabilitation using home ventilator, he successfully recovered without any pulmonary complications. The patient had complete symptom remission and no deterioration of Cobb's angle was found during follow-up.

Tumor Necrosis Factor Alpha Induces Neural Stem Cell Apoptosis Through Activating p38 MAPK Pathway.

Tumor necrosis factor alpha (TNF-α) is an essential cytokine that mediates cell death and has been shown to play a potential role in inducing neural stem cell (NSC) apoptosis. We have previously shown that TNF-α antagonist etanercept can suppress the transplanted NSC apoptosis induced by TNF-α in spinal cord injury (SCI) sites; however, the precise molecular mechanism remains unclear. This study aimed to investigate the signaling pathways responsible for TNF-α-induced apoptosis in NSCs. TNF-α treatment impairs cell viability and increases apoptosis of NSCs in concentration- and time-dependent manners. This is embodied in an increase in Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Additionally, TNF-α remarkably increased the expression of phosphatidylinositol p38 Mitogen-activated protein kinase (p38 MAPK) in NSCs. p38 MAPK regulates apoptosis, acting as an apoptotic signal due to TNF-α exposure. TNF-α-induced apoptosis was significantly alleviated by the p38 MAPK pathway inhibitor SB203580, as well as targeted inhibition of p38 gene in NSCs, or TNF-α antagonist etanercept. These results suggest that TNF-α induces NSCs apoptosis by activating the p38 MAPK signaling pathway and etanercept acts as an effective TNF-α antagonist to prevent p38 MAPK-dependent apoptosis induced by TNF-α in NSCs. Our research represents a potential gene targeting that can prevent unnecessary grafted cell death after transplantation into the SCI models.

The effects of intervertebral disc degeneration combined with osteoporosis on vascularization and microarchitecture of the endplate in rhesus monkeys.

PURPOSE: To evaluate the influence of osteoporosis on the microarchitecture and vascularization of the endplate in rhesus monkeys with or without intervertebral disc (IVD) degeneration using micro-computerized tomography (micro-CT), and to further analyze the correlation between osteoporosis and IVD degeneration. METHODS: Twelve rhesus monkeys were randomly divided into the ovariectomy (OVX, n = 6) and the sham group (n = 6). The subchondral bone adjacent to the lumbar IVDs (from L4/5 to L6/7) of each monkey was randomly injected with 4 ml pingyangmycin (PYM) solution (1.5 mg/ml, PYM), or 4 ml phosphate buffered saline (PBS) as vehicle treatment, or exteriorized but not injected anything as control (Cntrl). Degenerative and osteoporotic processes were evaluated at different time points. Micro-CT and histology were performed to analyze microarchitecture, calcification area and vascularization of the endplate. RESULTS: OVX resulted in significant decrease of bone mineral density (BMD). PYM injection induced progressively IVD degeneration, which was more progressive when combined with OVX. There was a negative correlation between BMD and Pfirrmann grade in the subgroups with PYM injection. The micro-CT analysis showed the combination of osteoporosis and IVD degeneration led to more calcification of endplate than any one thereof. The decrease of vascular volume percent in the endplate of the OVX-PYM subgroup was significantly greater than that in the Sham-PYM subgroup, both of which showed significant less vascularization compared to the other subgroups. CONCLUSION: In conclusion the osteoporosis could accumulate the calcification and decrease the vascularization in the endplates adjacent to the degenerated IVDs, which subsequently exacerbated degeneration of the degenerated IVDs.

Biomechanical evaluation of monosegmental pedicle instrumentation in a calf spine model and the role of fractured vertebrae in screw stability.

BACKGROUND: Monsegmental pedicle instrumentation (MSPI) has been used to treat thoracolumbar fractures. However, there are few reports about the biomechanical characteristics of MSPI compared with traditional short-segment pedicle instrumentation (SSPI) in management of unstable thoracolumbar fractures, and the influence of vertebral fracture on screw stability is still unclear. METHODS: This study was to compare the immediate stability between MSPI and SSPI in management of unstable L1 fracture, and to evaluate the role of fractured vertebrae in screw stability. Two studies were performed: in the first study, sixteen fresh calf spines (T11-L3) were divided into two groups, in which unstable fractures at L1 were produced and then instrumented with MSPI or SSPI respectively. The range of motion (ROM) and lax zone (LZ) of specimens were evaluated with pure moment of 6 Nm loaded. The second study measured and compared the pullout strength of screws inserted in to 16 intact and fractured vertebrae of calf spines (L1-3) respectively. The correlation of pullout strength with load sharing classification (LSC) of fractured vertebrae was analyzed. RESULTS: No significant difference in the ROM and LZ of the destabilized segments after fixation between MSPI and SSPI, except in axial rotation of ROM (P < 0.05). After fatigue cyclic loading, the MSPI showed a significant increase of ROM during lateral bending and axial rotation (P < 0.05); however, there were no significant differences in the LZ during all loading models between groups (P > 0.05). The mean pullout strength of pedicle screws in fractured vertebrae decreased by 13.7%, compared with that of intact vertebrae (P > 0.05), and had a low correlation with LSC of the fractured vertebrae (r = 0.293, P > 0.05). CONCLUSIONS: MSPI can provide effective immediate stability for management of unstable thoracolumbar fractures; however, it has less fatigue resistance during lateral bending and axial rotation compared with SSPI. LSC score of fractured vertebrae is not a major influence on the pullout strength of screws.

Cervical cage without plating in management of type II / II A Hangman's fracture combined with intervertebral disc injury.

BACKGROUND: Surgical intervention is increasingly performed as the primary treatment of unstable Hangman's fracture. Some authors have advocated using anterior C2/3 discectomy with interbody fusion and plating to treat unstable Hangman's fracture combined with intervertebral disc injury; however, there are few reports on unstable Hangman's fracture treated by anterior interbody fusion with the cervical cage (PEEK material) solely. METHODS: This study was to assess the efficacy of the cervical cage in management of unstable Hangman's fracture combined with intervertebral disc injury. A cohort of 15 patients with unstable Hangman's fractures fulfilling the inclusion criteria were prospectively submitted to surgical treatment of anterior C2/3 discectomy and interbody fusion using the cervical cage without plating. According to the Levine and Edwards classification, there were 5 type II, and 10 type IIA cases. The clinical outcome (the visual analog scale and the clinical post-traumatic neck score), radiological findings (angulation, translation, and disc height), and bone healing were assessed at 3, 6, 12, and 24 months. RESULTS: All the patients were followed up successfully. There were no intra- or postoperative complications observed. Solid fusion was achieved in all cases by 6 months after surgery. The local kyphotic angle was corrected significantly with the mean preoperative 12.31 ± 2.96 degrees, initial postoperative -1.98 ± 1.62 degrees and the latest follow-up -1.72 ± 1.60 degrees respectively (P < 0.05).The translation was also corrected significantly with the mean preoperative 3.20 ± 1.16 mm, initial postoperative 0.97 ± 0.36 mm, and the latest follow-up 1.05 ± 0.34 mm respectively (P < 0.05). The mean visual analog scale and the clinical post-traumatic neck score improved significantly following surgery (P < 0.05). CONCLUSIONS: This case series demonstrates that anterior C2/3 discectomy and interbody fusion with the cervical cage solely is effective and reliable in management of type II / IIA Hangman's fracture with C2/3 disc injury when properly indicated.