Anatomical Brushite-Coated Mg-Nd-Zn-Zr Alloy Cage Promotes Cervical Fusion: One-Year Results in Goats.

In this study, an anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage was fabricated for cervical fusion in goats. The purpose of this study was to investigate the cervical fusion effect and degradation characteristics of this cage in goats. The Mg-Nd-Zn-Zr alloy cage was fabricated based on anatomical studies, and brushite coating was prepared. Forty-five goats were divided into three groups, 15 in each group, and subjected to C2/3 anterior cervical decompression and fusion with tricortical bone graft, Mg-Nd-Zn-Zr alloy cage, or brushite-coated Mg-Nd-Zn-Zr alloy cage, respectively. Cervical radiographs and computed tomography (CT) were performed 3, 6, and 12 months postoperatively. Blood was collected for biocompatibility analysis and Mg2+ concentration tests. The cervical spine specimens were obtained at 3, 6, and 12 months postoperatively for biomechanical, micro-CT, scanning electron microscopy coupled with energy dispersive spectroscopy, laser ablation-inductively coupled plasma-time-of-flight mass spectrometry, and histological analysis. The liver and kidney tissues were obtained for hematoxylin and eosin staining 12 months after surgery for biosafety analysis. Imaging and histological analysis showed a gradual improvement in interbody fusion over time; the fusion effect of the brushite-coated Mg-Nd-Zn-Zr alloy cage was comparable to that of the tricortical bone graft, and both were superior to that of the Mg-Nd-Zn-Zr alloy cage. Biomechanical testing showed that the brushite-coated Mg-Nd-Zn-Zr alloy cage achieved better stability than the tricortical bone graft at 12 months postoperatively. Micro-CT showed that the brushite coating significantly decreases the corrosion rate of the Mg-Nd-Zn-Zr alloy cage. In vivo degradation analysis showed higher Ca and P deposition in the degradation products of the brushite-coated Mg-Nd-Zn-Zr alloy cage, and no hyperconcentration of Mg was detected. Biocompatibility analysis showed that both cages were safe for cervical fusion surgery in goats. To conclude, the anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage can promote cervical fusion in goats, and the brushite-coated Mg-Nd-Zn-Zr alloy is a potential material for developing absorbable fusion cages.

Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage.

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.

[Effect of "nape seven needles" on expression of hypoxia inducible factor-1α and Notch1 in cervical intervertebral disc degeneration rats].

OBJECTIVE: To observe the effect of "nape seven needles" on the expressions of hypoxia inducible factor-1α (HIF-1α) and Notch1 in cervical intervertebral disc of cervical disc degeneration (CDD) rats, so as to reveal its underlying mecha-nisms in improving CDD. METHODS: SD male rats were randomly divided into normal, model, non-acupoint and nape seven needles groups, with 10 rats in each group. Staticdynamic imbalance method was used to establish CDD model. Rats in the nape se-ven needles group were treated with acupuncture at "Fengfu"(GV16), and bilateral "Fengchi"(GB20), "Wangu"(GB12) and "Tianzhu"(BL10), and rats in the non-acupoint group received acupuncture at the sham acupoints at the caudal tip and armpit, both for 20 min, 6 days a week for 4 weeks. After intervention, tilted plane test and spiral CT were used to assess the neck movement function and cervical degeneration degree of rats; immunohistochemistry was used to observe the protein expression levels of HIF-1α and Notch1 in cervical discs tissue; Western blot and real-time quantitative PCR were used to detect the protein and mRNA expression levels of HIF-1α and Notch1 in cervical discs tissue, respectively. RESULTS: After modeling, the cervical curvature was straightened, with narrowed intervertebral space, rough and hardened articular surface, osteophytes, and blurred articular space and articular process, which was relatively milder in the nape seven needles group. Compared with the normal group, the angle of tilted plane was significantly reduced (P<0.05), while cervical scores, HIF-1α mRNA expression level in cervical intervertebral disc tissue were significantly increased (P<0.05) in the model group. Compared with the model and the non-acupoint groups, cervical scores were significantly reduced (P<0.05), while the angle of tilted plane, HIF-1α and Notch1 positive expressions, HIF-1α mRNA expression level, Notch1 protein and mRNA expression levels in cervical intervertebral disc tissue were significantly increased (P<0.05) in the nape seven needles group. CONCLUSION: Acupuncture of "nape seven needles" can reduce the degree of cervical degeneration in rats, which was possibly associated with its effects in up-regulating the expressions of HIF-1α and Notch1 in cervical intervertebral disc tissue, promoting the proliferation and recovery of endogenous cells in nucleus pulposus.

The Effect of the NFκB-USP9X-Cx43 Axis on the Dynamic Balance of Bone Formation/Degradation during Ossification of the Posterior Longitudinal Ligament of the Cervical Spine.

Connexin 43- (Cx43-) mediated nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling has been found involved in the ossification of the posterior longitudinal ligament (OPLL). However, the underlying mechanism how OPLL is regulated has not been elucidated. In the present study, primary ligament fibroblast were isolated; immunoprecipitation (IP) and liquid chromatography-mass spectrometry (LC-MS) assays were applied to identify potential binding proteins of Cx43. Protein interaction was then confirmed by co-IP assay. Alkaline phosphatase (ALP) activity and alizarin red staining were used to evaluate ossification. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to assess the binding between NF-κB p65 and target gene. Lipoxygenase inhibitor (5,8,11-eicosatriynoic acid, EPA) was applied to induce endoplasmic reticulum (ER) stress, and 4-phenylbutyrate (4-PBA) was used as an ER-stress inhibitor. Expression of USP9X, Cx43, and nuclei p65 in ligaments from patients and controls was detected by Western blotting. The results showed that ubiquitin-specific protease 9 X-chromosome (USP9X), a deubiquitylating enzyme, was a candidate of Cx43 binding proteins, and USP9X inhibited Cx43 ubiquitination. In vitro experiments showed that USP9X promoted ossification of primary ligament fibroblasts and nuclear translocation of NF-κB p65 by regulating Cx43 expression. Moreover, NF-κB can bind to the USP9X promoter to promote its transcription. When ER stress was inhibited by 4-PBA, USP9X levels, NF-κB nuclei translocation, and ALP activity were decreased. Reverse results were obtained when ER stress was induced by EPA. PDTC, an NF-κB inhibitor, could abolish the effects of EPA. Furthermore, USP9X, Cx43, and nuclei p65 were significantly upregulated in ligaments from OPLL patients than non-OPLL controls. USP9X was positively correlated with CX43 and nuclei p65 in OPLL samples. Overall, the findings suggest that the ER stress-NFκB-USP9X-Cx43 signaling pathway plays an important role in OPLL progression.

Fatty infiltration in cervical flexors and extensors in patients with degenerative cervical myelopathy using a multi-muscle segmentation model.

BACKGROUND: In patients with degenerative cervical myelopathy (DCM) that have spinal cord compression and sensorimotor deficits, surgical decompression is often performed. However, there is heterogeneity in clinical presentation and post-surgical functional recovery. OBJECTIVES: Primary: a) to assess differences in muscle fat infiltration (MFI) in patients with DCM versus controls, b) to assess association between MFI and clinical disability. Secondary: to assess association between MFI pre-surgery and post-surgical functional recovery. STUDY DESIGN: Cross-sectional case control study. METHODS: Eighteen patients with DCM (58.6 ± 14.2 years, 10 M/8F) and 25 controls (52.6 ± 11.8 years, 13M/12 F) underwent 3D Dixon fat-water imaging. A convolutional neural network (CNN) was used to segment cervical muscles (MFSS- multifidus and semispinalis cervicis, LC- longus capitis/colli) and quantify MFI. Modified Japanese Orthopedic Association (mJOA) and Nurick were collected. RESULTS: Patients with DCM had significantly higher MFI in MFSS (20.63 ± 5.43 vs 17.04 ± 5.24, p = 0.043) and LC (18.74 ± 6.7 vs 13.66 ± 4.91, p = 0.021) than controls. Patients with increased MFI in LC and MFSS had higher disability (LC: Nurick (Spearman's ρ = 0.436, p = 0.003) and mJOA (ρ = -0.399, p = 0.008)). Increased MFI in LC pre-surgery was associated with post-surgical improvement in Nurick (ρ = -0.664, p = 0.026) and mJOA (ρ = -0.603, p = 0.049). CONCLUSION: In DCM, increased muscle adiposity is significantly associated with sensorimotor deficits, clinical disability, and functional recovery after surgery. Accurate and time efficient evaluation of fat infiltration in cervical muscles may be conducted through implementation of CNN models.

Diffuse Idiopathic Skeletal Hyperostosis of Cervical Spine with Dysphagia-Molecular and Clinical Aspects.

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the calcification and ossification of the ligaments of the cervical spine; in some cases, it may result in dysphagia. The condition is more common in men over 50 years of age with metabolic disorders, and it is often asymptomatic and not a major issue for patients. The etiology of DISH is poorly understood, and known genetic factors indicate multiple signal pathways and multigene inheritance. In this review, we discuss the epidemiological, clinical, and etiological aspects of DISH with a special focus on dysphagia.

A potential defense mechanism against amyloid deposition in cerebellum.

Amyloid-ß (Aß) is the major component of senile plaques in Alzheimer's disease (AD) brains. Senile plaques are generally observed in cerebral cortex (CTX) rather than cerebellum (CBL) in AD patients. However, it is not clear why CBL has less Aß deposition than CTX. It is very important to elucidate the mechanism of suppressing Aß deposition in CBL, because it contributes to understanding of not only AD pathogenesis but also prevention and cure of AD. In this study, we explored to figure out the potential mechanism of reducing Aß deposition in CBL. We observed higher age-dependent elevation of Aß level in CTX rather than CBL of human APP knock-in AD model mice, although we detected no significant differences in the levels of interstitial fluid Aß in these brain tissues. These data imply that less Aß deposition in CBL is due to enhanced Aß clearance rather than altered Aß production in CBL. To gain insights into Aß clearance in CBL, we injected fluorescence-labeled Aß in brain tissues. Importantly diffusion area of fluorescent Aß in CBL was roughly six-times larger than that in CTX within 2 h of injection. In addition, injected Aß area in CBL decreased sharply after 24 h and CBL-injected Aß was robustly detected in deep cervical lymph nodes (DcLNs). In contrast, diffusion area of fluorescent Aß in CTX was consistent up to 72 h and CTX-injected Aß was faintly detected in DcLNs. Our data suggest that enhanced Aß drainage in association with meningeal lymphatic system is responsible for less Aß deposition in CBL.

Expanding the phenotype of Wiedemann-Steiner syndrome: Craniovertebral junction anomalies.

Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant condition caused by heterozygous loss of function variants in the KMT2A (MLL) gene, encoding a lysine N-methyltransferase that mediates a histone methylation pattern specific for epigenetic transcriptional activation. WDSTS is characterized by a distinctive facial phenotype, hypertrichosis, short stature, developmental delay, intellectual disability, congenital malformations, and skeletal anomalies. Recently, a few patients have been reported having abnormal skeletal development of the cervical spine. Here we describe 11 such individuals, all with KMT2A de novo loss-of-function variants: 10 showed craniovertebral junction anomalies, while an 11th patient had a cervical abnormality in C7. By evaluating clinical and diagnostic imaging data we characterized these anomalies, which consist primarily of fused cervical vertebrae, C1 and C2 abnormalities, small foramen magnum and Chiari malformation type I. Craniovertebral anomalies in WDSTS patients have been largely disregarded so far, but the increasing number of reports suggests that they may be an intrinsic feature of this syndrome. Specific investigation strategies should be considered for early identification and prevention of craniovertebral junction complications in WDSTS patients.

Zonisamide ameliorates progression of cervical spondylotic myelopathy in a rat model.

Cervical spondylotic myelopathy (CSM) is caused by chronic compression of the spinal cord and is the most common cause of myelopathy in adults. No drug is currently available to mitigate CSM. Herein, we made a rat model of CSM by epidurally implanting an expanding water-absorbent polymer underneath the laminae compress the spinal cord. The CSM rats exhibited progressive motor impairments recapitulating human CSM. CSM rats had loss of spinal motor neurons, and increased lipid peroxidation in the spinal cord. Zonisamide (ZNS) is clinically used for epilepsy and Parkinson's disease. We previously reported that ZNS protected primary spinal motor neurons against oxidative stress. We thus examined the effects of ZNS on our rat CSM model. CSM rats with daily intragastric administration of 0.5% methylcellulose (n = 11) and ZNS (30 mg/kg/day) in 0.5% methylcellulose (n = 11). Oral administration of ZNS ameliorated the progression of motor impairments, spared the number of spinal motor neurons, and preserved myelination of the pyramidal tracts. In addition, ZNS increased gene expressions of cystine/glutamate exchange transporter (xCT) and metallothionein 2A in the spinal cord in CSM rats, and also in the primary astrocytes. ZNS increased the glutathione (GSH) level in the spinal motor neurons of CSM rats. ZNS potentially ameliorates loss of the spinal motor neurons and demyelination of the pyramidal tracts in patients with CSM.

Expression Analysis of Susceptibility Genes for Ossification of the Posterior Longitudinal Ligament of the Cervical Spine in Human OPLL-related Tissues and a Spinal Hyperostotic Mouse (ttw/ttw).

STUDY DESIGN: Immunohistochemical and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. OBJECTIVE: The aim of this study was to analyze the expression of five susceptibility genes (RSPO2, HAO1, CCDC91, RHPH9, and STK38L) for human ossification of the posterior longitudinal ligaments (OPLL) identified in a genome-wide association study. SUMMARY OF BACKGROUND DATA: Detailed expression and functional studies for the five susceptibility genes are needed to aid in clarification of the etiology and pathogenesis of OPLL. METHODS: Immunostaining, cell culture, and real-time RT-PCR were performed on ossified ligament samples collected during anterior cervical decompression for symptomatic OPLL (n = 39 patients) and on control non-OPLL samples (n = 8 patients). Immunohistochemical analysis in spinal hyperostotic mice (ttw/ttw) (n = 25) was also performed. The sample sections were stained for RSPO2, HAO1, CCDC91, RHPH9, STK38L, Runx2, Sox9, and CD90. The mRNA expression levels of the five susceptibility genes were also analyzed in cultured human OPLL and non-OPLL cells subjected to cyclic tensile strain. RESULTS: Immunoreactivity for RSPO2 and Sox9 was evident in proliferating chondrocytes in human OPLL tissues and ttw/ttw mice. Application of cyclic tensile strain to cultured human OPLL cells resulted in increases in mRNA levels for RSPO2, HAO1, and CCDC91. However, individual differences in expression in human OPLL-related samples were seen. HAO1-positive cells were detected only in 3- to 6-week-old ttw/ttw mice that did not simultaneously express RSPO2-positive samples. CONCLUSION: Among the five susceptibility genes, RSPO2, HAO1, and CCDC91 might be contributory factors in progression of OPLL. RSPO2 may be involved in endochondral ossification, especially in mixed or continuous type OPLL, HAO1 may be an initiation factor for OPLL that is rarely seen in mature human OPLL samples, and CCDC91 may be associated with progression of ossification caused by mechanical stress. These findings provide important insights into the pathogenesis and therapeutic targets for OPLL. LEVEL OF EVIDENCE: N/A.

Solitary vertebral metastatic glioblastoma in the absence of primary brain tumor relapse: a case report and literature review.

BACKGROUND: Metastatic glioblastoma presenting as a solitary osteolytic cervical vertebral mass without primary brain tumor relapse is extremely rare with only 1 reported case in the literature. Because of its rarity, it can be easily overlooked and misdiagnosed, posing a diagnostic dilemma. CASE PRESENTATION: A 51-year-old man with right temporal glioblastoma was initially treated by tumor resection, radiotherapy and chemotherapy. Eighteen months after surgery, he was readmitted with complaints of neck pain for 2 weeks. Follow-up magnetic resonance imaging (MRI) and fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed a solitary FDG-avid osteolytic lesion in the 4th cervical vertebral body without other abnormal FDG-uptake in the body and in the absence of local recurrence at the resection cavity. Because of the sudden worsening situation and intractable neck pain, the patient underwent tumor resection. Postoperatively, the pain was obviously reduced and the situation was improved. Interestingly, the immunohistochemical findings of glial fibrillary acidic protein (GFAP) indicated the characteristic of metastatic glioblastoma, despite that the histopathological findings of Hematoxylin & Eosin (H&E) staining was suspicious of osteoclastoma. According to the clinical history, imaging findings, pathological and immunohistochemical results, a final diagnosis of solitary vertebral metastasis from glioblastoma without central nervous system (CNS) relapse was confirmed. Then, the patient received radiotherapy on spine and adjuvant chemotherapy with temozolomide. However, he died suddenly 2 months after the tumor resection, nearly 21 months after the initial diagnosis. CONCLUSION: We emphasize that metastatic glioblastoma should be considered in the differential diagnosis of a solitary FDG-avid osteolytic vertebral mass on PET/CT. And the diagnosis of extracranial metastasis (ECM) from glioblastoma can be achieved through clinical history, imaging findings, pathological examination, and immunohistochemical staining with GFAP.

Confirming the geography of fatty infiltration in the deep cervical extensor muscles in whiplash recovery.

Previous preliminary work mapped the distribution of neck muscle fat infiltration (MFI) in the deep cervical extensor muscles (multifidus and semispinalis cervicis) in a small cohort of participants with chronic whiplash associated disorders (WAD), recovered, and healthy controls. While MFI was reported to be concentrated in the medial portion of the muscles in all participants, the magnitude was significantly greater in those with chronic WAD. This study aims to confirm these results in a prospective fashion with a larger cohort and compare the findings across a population of patients with varying levels of WAD-related disability one-year following the motor vehicle collision. Sixty-one participants enrolled in a longitudinal study: Recovered (n = 25), Mild (n = 26) and Severe WAD (n = 10) were studied using Fat/Water magnetic resonance imaging, 12-months post injury. Bilateral measures of MFI in four quartiles (Q1-Q4; medial to lateral) at cervical levels C4 through C7 were included. A linear mixed model was performed, controlling for covariates (age, sex, body mass index), examining interaction effects, and comparing MFI distribution between groups. The recovered group had significantly less MFI in Q1 compared to the two symptomatic groups. Group differences were not found in the more lateral quartiles. Results at 12 months are consistent with the preliminary study, indicating that MFI is spatially concentrated in the medial portions of the deep cervical extensors regardless of WAD recovery, but the magnitude of MFI in the medial portions of the muscles is significantly larger in those with severe chronic WAD.

Immuohistochemical score of matrix metalloproteinase-1 may indicate the severity of symptomatic cervical and lumbar disc degeneration.

BACKGROUND CONTEXT: Intervertebral disc (IVD) degeneration is related to numerous risk factors, including obesity. Leptin, one of the commonly measured adipokines, is proven to play an important role in the pathogenesis of IVD degeneration. In the context of IVD degeneration, matrix metalloproteinase-1 (MMP-1), which is upregulated and activated by leptin, is the most abundant catabolic enzyme. It remains unclear which of the factors mentioned above is most strongly associated with IVD degeneration. PURPOSE: To investigate the influence of MMP-1 in IVD degeneration, we determined the strength of different predictors, including age, sex, magnetic resonance imaging (MRI), Modic changes (MCs), body mass index (BMI), leptin, and MMP-1. This was achieved by assessing the correlation among these factors and histologic degeneration score (HDS). STUDY DESIGN: This study included 89 patients undergoing cervical discectomy for disc herniation, 93 who underwent lumbar discectomy, and 90 control subjects. Herniated disc tissue and plasma were used after the study was approved by the Human Ethics Review Committee at the authors' institution. METHODS: Hematoxylin and eosin (H&E), Alcian blue-PAS and immunohistochemical (IHC) staining were performed to measure the expression levels of leptin and MMP-1. Circulating plasma levels of leptin and MMP-1 were measured using an enzyme-linked immunosorbent assay. To assess the correlation with HDS, measurements of age, sex, BMI, MRI scale, MCs scale, leptin/MMP-1 plasma concentration, and leptin/MMP-1 IHC expression were analyzed. RESULTS: Patients with cervical or lumbar discectomy had significantly higher BMI than controls. Significantly more men than women were involved in the lumbar patients as compared with the cervical patients and the control subjects. After adjustment for age and sex, plasma leptin and leptin IHC score correlated significantly with BMI in patients with cervical or lumbar discectomy. Age, sex, MRI scale, MCs scale, and leptin/MMP-1 plasma concentration were not positively correlated with HDS. HDS was significantly associated with BMI, leptin IHC score, and MMP-1 IHC score. After a stepwise-multiple linear regression analysis to evaluate the strength of the correlations between HDS and various factors, only the MMP-1 IHC score demonstrated an independent association with HDS in patients with degeneration of the cervical or lumbar disc. CONCLUSIONS: MMP-1 IHC score is an independent predictor of the severity of cervical or lumbar IVD degeneration. CLINICAL SIGNIFICANCE: MMP-1 IHC score may be used as an indicator of IVD degeneration.

Sleep disordered breathing induced by cervical spinal cord injury and effect of adenosine A1 receptors modulation in rats.

Sleep-disordered breathing (SDB) is very common after spinal cord injury (SCI). The present study was designed to evaluate the therapeutic efficacy of adenosine A1 receptor blockade (8-cyclopentyl-1,3-dipropylxanthine, DPCPX) on SDB in a rodent model of SCI. We hypothesized that SCI induced via left hemisection of the second cervical segment (C2Hx) results in SDB. We further hypothesized that blockade of adenosine A1 receptors following C2Hx would reduce the severity of SDB. In the first experiment, adult male rats underwent left C2Hx or sham (laminectomy) surgery. Unrestrained whole body plethysmography (WBP) and implanted wireless electroencephalogram (EEG) were used for assessment of breathing during spontaneous sleep and for the scoring of respiratory events at the acute (~1 wk), and chronic (~6 wk) time points following C2Hx. During the second experiment, the effect of oral administration of adenosine A1 receptor antagonist (DPCPX, 3 times a day for 4 days) on SCI induced SDB was assessed. C2Hx animals exhibited a higher apnea-hypopnea index (AHI) compared with the sham group, respectively (35.5 ± 12.6 vs. 19.1 ± 2.1 events/h, P < 0.001). AHI was elevated 6 wk following C2Hx (week 6, 32.0 ± 5.0 vs. week 1, 42.6 ± 11.8 events/h, respectively, P = 0.12). In contrast to placebo, oral administration of DPCPX significantly decreased AHI 4 days after the treatment (159.8 ± 26.7 vs. 69.5 ± 8.9%, P < 0.05). Cervical SCI is associated with the development of SDB in spontaneously breathing rats. Adenosine A1 blockade can serve as a therapeutic target for SDB induced by SCI.NEW & NOTEWORTHY The two key novel findings of our study included that 1) induced cervical spinal cord injury results in sleep-disordered breathing in adult rats, and 2) oral therapy with an adenosine A1 receptor blockade using DPCPX is sufficient to significantly reduce apnea-hypopnea index following induced cervical spinal cord injury.

The correlation between hypoxia-inducible factor-1α, matrix metalloproteinase-9 and functional recovery following chronic spinal cord compression.

The molecular mechanisms underlying cervical spondylotic myelopathy (CSM) are poorly understood. To assess the correlation between HIF-1α, MMP-9 and functional recovery following chronic cervical spinal cord compression (CSCI). Rats in the sham group underwent C5 semi-laminectomy, while a water-absorbable polyurethane polymer was implanted into the C6 epidural space in the chronic CSCI group. Basso, Beattie and Bresnahan score and somatosensory evoked potentials were used to evaluate neurological function. Hematoxylin and eosin staining was performed to assess pathological changes in the spinal cord, while immunohistochemical analysis was used to examine HIF-1α and MMP-9 expression on days 7, 28, 42 and 70 post-surgery. Normal rats were only used for HE staining. The BBB score was significantly reduced on day 28 following CSCI, while SEPs exhibited decreased amplitude and increased latency. In chronic CSCI group, the BBB score and SEPs significantly improved on day 70 compared with day 28. HE staining revealed different level of spinal cord edema after chronic CSCI. Compared with the sham group, immunohistochemical analyses revealed that HIF-1α- and MMP-9-positive cells were increased on day 7 and peaked on day 28. HIF-1α and MMP-9 expression were demonstrated to be significantly positively correlated, whereas HIF-1α expression and BBB score were significantly negatively correlated, as well MMP-9 expression and BBB score. HIF-1α and MMP-9 expression are increased following chronic spinal cord compression and are positively correlated with one another. Decreased expression of HIF-1α and MMP-9 may contribute to functional recovery following CSCI. This expression pattern of HIF-1α and MMP-9 may give a new perspective on the molecular mechanisms of CSM.

A study of the factors associated with cervical spinal disc degeneration, with a focus on bone metabolism and amino acids, in the Japanese population: a cross sectional study.

BACKGROUND: The physical and biochemical factors responsible for cervical disc degeneration, and resulting in various spinal disorders, remain unclear. This study aimed to evaluate the correlation between cervical spinal canal stenosis and degeneration of intervertebral discs, and to analyze the factors related to disc degeneration in the Japanese population. METHODS: Three hundred and forty-four Japanese general residents underwent investigations, including magnetic resonance imaging of the cervical spine, in our health check project. We measured anteroposterior diameters at the levels of the cervical spinal disc in mid sagittal plane magnetic resonance imaging and evaluated disc degeneration. Spearman correlation coefficient was used to evaluate whether the diameters were correlated with disc degenerative scores. Stepwise multiple linear regression analysis was conducted with the score of disc degeneration as the dependent variable; and age, physical measurement values, bone mineral density of the forearm, and the value of serum bone metabolic markers and amino acids as the independent variables for each sex. RESULTS: As the age increased, the anteroposterior diameters decreased in both sexes. The minimum anteroposterior diameters were correlated with the disc degenerative scores (Spearman r = - 0.59, p < 0.001 in men, Spearman r = - 0.53, p < 0.001 in women). In multiple linear regression analysis, age, cross-linked N-telopeptide of type 1 collagen and isoleucine were significantly correlated with the cervical disc degenerative score in men (R2 = 0.47), and age and lysine were significantly correlated with the degenerative score in women (R2 = 0.50). CONCLUSION: The factors responsible for cervical disc degeneration differed between men and women. Whether modifying these significant factors is possible, or whether this intervention would contribute to prevention of disc degeneration requires future studies.

Quantitative analysis of near-implant magnesium accumulation for a Si-containing coated AZ31 cage from a goat cervical spine fusion model.

BACKGROUND: Magnesium (Mg) released from Mg-based implants degradation is believed to be effective in improving osteogenesis, however, studies focusing on Mg-based interbody cages are limited and fusion success was never reported. As excessive Mg accumulation can inhibit new bone formation, this study is designed to explain the possible reasons for the fusion failure of Mg-based cages by analyzing the relationships between the intervertebral Mg accumulation and the resulting interbody fusion. METHODS: The experimental cage was consisted of magnesium alloy (AZ31) substrate and Silicon (Si) -containing coating. C3/C4 and C5/C6 of 24 goats were implanted with cage or autologous iliac crest bone graft (Control group), which were analyzed at 3, 6, 12, and 24 weeks post-operatively. Intervertebral Mg concentrations, Mg-related Calcium (Ca)/ Phosphorus (P) ratios, radiological evaluations and histological findings were recorded for analyzing the relationships between the three of cage corrosion, Mg accumulation, and interbody fusion. RESULTS: Intervertebral Mg levels were significantly increased after cage implantation, especially in the areas that were closer to the cages at 3 weeks post-operatively, and these increased concentrations could persist up to 12 weeks post-operatively, indicating a relatively rapid corrosion process. Significantly lower Mg levels were only found at 24 weeks post-operatively, but these levels were still higher than those of the control group. In addition, Mg was found to be widely distributed at the intervertebral space since high Mg concentrations could even be detected at the posterior boundary of the vertebral body. Under this Mg accumulation profile, interbody fusion was not achieved, as indicated by the decreased Ca/P ratios, low CT fusion scores and negative histological results. CONCLUSIONS: Intervertebral excessive Mg accumulation might be the primary reason for interbody fusion failure. Quantitative Mg analysis can offer insight into the association between cage degeneration and biological response.

Physiological uptake of 18F-FDG in the vertebral bone marrow in healthy adults on PET/CT imaging.

BACKGROUND: 18F-fluorodeoxyglucose *Equal contributors. positron emission tomography/computed tomography (18F-FDG PET/CT) has proven to be a valuable imaging modality for the assessment of bone marrow condition. PURPOSE: To investigate the physiological uptake of 18F-FDG in the vertebral bone marrow in healthy adults on PET/CT imaging, and correlate the appearance with clinical factors including gender, body mass index, and age. MATERIAL AND METHODS: A total of 64 healthy individuals underwent PET/CT scan, and for each vertebral body, the mean and maximum standardized uptake value (SUVmean and SUVmax) were determined in the central slice of vertebral body on the transversal fused PET/CT image. For each individual, the FDG uptake of the four regions was obtained by averaging the SUVmean and SUVmax of the vertebrae in individual regions. RESULTS: The FDG uptake from thoracic to sacral vertebrae showed an upward trend first, then a downward trend, while that of cervical vertebrae was relatively stable. The SUVmax and SUVmean values of bone marrow in the old group (age ≥ 50 years) were significantly lower than those in the young group (age < 50 years) in all regions of the spine ( P < 0.05). FDG uptake of the whole spine showed significant negative correlation with age, and the strongest correlation was observed in lumbar spine (SUVmean: r = -0.364, P < 0.05; SUVmax: r = -0.344, P < 0.05). CONCLUSION: FDG uptake showed a tendency to increase first then decrease from thoracic to sacral vertebrae while the tendency was not obvious in cervical vertebrae. In addition, the glycolytic metabolism of all the four regions decreased with advancing age.

Evaluation of a Porous Bioabsorbable Interbody Mg-Zn Alloy Cage in a Goat Cervical Spine Model.

PURPOSE: Bioabsorbable Mg-based implants were previously assessed due to their intrinsic advantages, but Mg-based cage related research is limited. The specific blood supply and stress of the intervertebral environment can affect the function of Mg-based implants. The objective of this study was to investigate the performance of a bioabsorbable Mg-Zn alloy cage in anterior cervical discectomy and fusion (ACDF) and evaluate the control of degradation of the Mg-Zn cage surface modified by microarc oxidation (MAO) technology containing Si under an intervertebral microenvironment. METHODS: Twenty-four goats were divided into four groups according to the experimental period and all underwent ACDF at C2-3 and C4-5 with porous Mg-Zn cage covered with a MAO/Si-containing coating in one intervertebral space and with autologous iliac bone in another space. After 3, 6, 12, or 24 weeks after operation, the cervical spine specimens were harvested to evaluate the biocompatibility, fusion status, and degradation conditions using blood analysis, radiology, biomechanical testing, histology, and micro-CT. RESULTS: The Mg-Zn cages showed ideal biocompatibility and biomechanical characterization; however, the fusion state, as evaluated with radiology and histology, was not acceptable. Modified by the MAO/Si-containing coating, the degradation rate of the Mg-Zn cages was controllable but slower than expected. CONCLUSION: MAO/Si-containing coating Mg-Zn alloy cages demonstrated excessive control of degradation and fusion failure after 24 weeks postoperatively. We conclude that further studies should be designed to improve the using of Mg-based materials at the intervertebral space.

Inflammaging in cervical and lumbar degenerated intervertebral discs: analysis of proinflammatory cytokine and TRP channel expression.

PURPOSE: To investigate and compare the occurrence of inflammatory processes in the sites of disc degeneration in the lumbar and cervical spine by a gene array and subsequent qPCR and to investigate the mechanistic involvement of transient receptor potential channels TRPC6 and TRPV4. METHODS: The gene expression of inflammatory cytokines and TRP channels was measured in human disc samples obtained from patients undergoing discectomy at the cervical (n = 24) or lumbar (n = 27) spine for degenerative disc disease (DDD) and disc herniation (DH) and analyzed for differences with regard to spinal level, IVD degeneration grade, Modic grade, age, sex, disc region and surgical extent. RESULTS: Aside from genes with known implication in DDD and DH, four previously unreported genes from the interferon and TRP families (IFNA1, IFNA8, IFNB1, TRPC6) could be detected. A correlation between gene expression and age (IL-15) and IVD degeneration grade (IFNA1, IL-6, IL-15, TRPC6), but not Modic grade, was identified. Significant differences were detected between cervical and lumbar discs (IL-15), nucleus and annulus (IL-6, TNF-α, TRPC6), single-level and multi-level surgery (IL-6, IL-8) as well as DDD and DH (IL-8), while sex had no effect. Multiple gene-gene pair correlations, either between different cytokines or between cytokines and TRP channels, exist in the disc. CONCLUSION: This study supports the relevance of IL-6 and IL-8 in disc diseases, but furthermore points toward a possible pathological role of IL-15 and type I interferons, as well as a mechanistic role of TRPC6. With limited differences in the inflammatory profile of cervical and lumbar discs, novel anti-inflammatory or TRP-modulatory strategies for the treatment of disc pathologies may be applicable independent of the spinal region.