The role of melatonergic system in intervertebral disc degeneration and its association with low back pain: a clinical study.

Objective: The mechanisms of intervertebral disc degeneration (IVDD) in low back pain (LBP) patients are multiples. In this study, we attempt to investigate whether melatonergic system plays a potential role in IVDD patients with LBP by analyzing their clinical specimens. The fucus will be given to the correlation between the melatonin receptor expression and intervertebral disc tissue apoptosis. Methods: In this clinical study, 107 lumbar intervertebral disc nucleus pulposus (NP) specimens from patients with LBP were collected with patients' consents. The disc height (DH) discrepancy ratio, range of motion and sagittal parameters of the pathological plane were measured and Pfirrmann grade was used to classified the grades of IVDD level. Discs at grades 1-3 were served as normal control and grades 4-5 were considered as IVDD. The expression levels of melatonin receptor 1A (MT1) and 1B (MT2) were measured by immunohistochemistry. The apoptosis of NP was assessed using TUNEL staining. Their potential associations among MT1/2, DH, apoptosis, sagittal parameters with IVDD and LBP were evaluated with statistical analysis. Results: The incidence of IVDD was positively associated with age and negatively related to VAS scores for LBP (p < 0.001). Patients with higher degree of IVDD also have higher DH discrepancy ratio (p < 0.001), higher prevalence of lumbar instability (p = 0.003) and higher cell apoptosis compared to the control. Nevertheless, no statistically significant correlation was identified between Pfirrmann grade and lumbar sagittal parameters. MT1 and MT2 both were highly expressed in the NP tissues. Importantly, MT1 expression but not MT2 was significantly increased in the intervertebral disc tissue of patients with IVDD and its level correlated well with cell apoptosis level and the severity of IVDD as well as lower VAS scores for LBP. Conclusion: The highly elevated MT1 expression was found in NP tissues of patients with IVDD and LBP compared to the control. This phenomenon probably reflects the compensating response of the body to the pathological alteration of the IVDD and LBP. Therefore, these findings provide the novel information to use selective agonists of MT1 to target IVDD and LBP clinically.

Sustained delivery of NT-3 and curcumin augments microenvironment modulation effects of decellularized spinal cord matrix hydrogel for spinal cord injury repair.

Decellularized extracellular matrix hydrogel, especially that derived from spinal cord (DSCM hydrogel), has been actively considered as a functional biomaterial for remodeling the extracellular matrix of the native tissue, due to its unique characteristics in constructing pro-regenerative microenvironment for neural stem cells (NSCs). Furthermore, DSCM hydrogel can provide multiple binding domains to growth factors and drugs. Therefore, both exogenous neurotrophic factors and anti-inflammatory drugs are highly desired to be incorporated into DSCM hydrogel, which may synergistically modulate the complex microenvironment at the lesion site after spinal cord injury (SCI). Herein, neurotrophin-3 (NT-3) and curcumin (Cur) were integrated into DSCM hydrogel for SCI therapy. Due to different affinities to the DSCM hydrogel, NT-3 underwent a controlled release manner, while curcumin released explosively within the first 24 h, followed by rather sustained but slower release. The integration of both NT-3 and curcumin significantly enhanced NSCs proliferation and their neuronal differentiation. Meanwhile, the release of curcumin promoted macrophages polarization into anti-inflammatory subtypes, which further facilitated NSCs differentiation into neurons. The in situ injected DSCM + NT3 + Cur hydrogel exerted superior capability in alleviating the inflammatory responses in rat contused spinal cord. Compared to DSCM hydrogel alone, DSCM + NT3 + Cur hydrogel more significantly promoted the recruitment of NSCs and their neuronal differentiation at the lesion site. These outcomes favored functional recovery, as evidenced by the improved hind limb movement. Overall, the bioactive DSCM hydrogel can serve as a multifunctional carrier for cooperatively release of growth factors and drugs, which significantly benefits microenvironment regulation and nerve regeneration after SCI.

Deep Learning-Enhanced Hand Grip and Release Test for Degenerative Cervical Myelopathy: Shortening Assessment Duration to 6 Seconds.

OBJECTIVE: Hand clumsiness and reduced hand dexterity can signal early signs of degenerative cervical myelopathy (DCM). While the 10-second grip and release (10-s G&R) test is a common clinical tool for evaluating hand function, a more accessible method is warranted. This study explores the use of deep learning-enhanced hand grip and release test (DL-HGRT) for predicting DCM and evaluates its capability to reduce the duration of the 10-s G&R test. METHODS: The retrospective study included 508 DCM patients and 1,194 control subjects. Propensity score matching (PSM) was utilized to minimize the confounding effects related to age and sex. Videos of the 10-s G&R test were captured using a smartphone application. The 3D-MobileNetV2 was utilized for analysis, generating a series of parameters. Additionally, receiver operating characteristic curves were employed to assess the performance of the 10-s G&R test in predicting DCM and to evaluate the effectiveness of a shortened testing duration. RESULTS: Patients with DCM exhibited impairments in most 10-s G&R test parameters. Before PSM, the number of cycles achieved the best diagnostic performance (area under the curve [AUC], 0.85; sensitivity, 80.12%; specificity, 74.29% at 20 cycles), followed by average grip time. Following PSM for age and gender, the AUC remained above 0.80. The average grip time achieved the highest AUC of 0.83 after 6 seconds, plateauing with no significant improvement in extending the duration to 10 seconds, indicating that 6 seconds is an adequate timeframe to efficiently evaluate hand motor dysfunction in DCM based on DL-HGRT. CONCLUSION: DL-HGRT demonstrates potential as a promising supplementary tool for predicting DCM. Notably, a testing duration of 6 seconds appears to be sufficient for accurate assessment, enhancing the test more feasible and practical without compromising diagnostic performance.

The ferroptosis activity is associated with neurological recovery following chronic compressive spinal cord injury.

Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase, followed by partial self-recovery, and ultimately an equilibrium state of neurological dysfunction. Ferroptosis is a crucial pathological process in many neurodegenerative diseases; however, its role in chronic compressive spinal cord injury remains unclear. In this study, we established a chronic compressive spinal cord injury rat model, which displayed its most severe behavioral and electrophysiological dysfunction at 4 weeks and partial recovery at 8 weeks after compression. Bulk RNA sequencing data identified enriched functional pathways, including ferroptosis, presynapse, and postsynaptic membrane activity at both 4 and 8 weeks following chronic compressive spinal cord injury. Transmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression. Ferroptosis activity was negatively correlated with behavioral score. Immunofluorescence, quantitative polymerase chain reaction, and western blotting showed that expression of the anti-ferroptosis molecules, glutathione peroxidase 4 (GPX4) and MAF BZIP transcription factor G (MafG), in neurons was suppressed at 4 weeks and upregulated at 8 weeks following spinal cord compression. There was a positive correlation between the expression of these two molecules, suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury. In conclusion, our study determined the genome-wide expression profile and ferroptosis activity of a consistently compressed spinal cord at different time points. The results showed that anti-ferroptosis genes, specifically GPX4 and MafG, may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury. These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy.

Electrophysiological evidence of diabetes' impacts on central conduction recoveries in degenerative cervical myelopathy after surgery.

OBJECTIVES: To assess the impact of diabetes mellitus (DM) on the postoperative motor and somatosensory functional recoveries of degenerative cervical myelopathy (DCM) patients. METHODS: Motor and somatosensory evoked potentials (MEP and SSEPs) and modified Japanese Orthopedic Association (mJOA) scores were recorded in 27 diabetic (DCM-DM group) and 38 non-diabetic DCM patients (DCM group) before and 1 year after surgery. The central motor (CMCT) and somatosensory (CSCT) conduction time were recorded to evaluate the conductive functions of the spinal cord. RESULTS: The mJOA scores, CMCT and CSCT improved (t test, p < 0.05) in both of the DCM-DM and DCM groups 1 year after surgery. The mJOA recovery rate (RR) and CSCT recovery ratio were significantly worse (t test, p < 0.05) in the DCM-DM group compared to the DCM group. DM proved to be a significant independent risk factor for poor CSCT recovery (OR = 4.52, 95% CI 2.32-7.12) after adjusting for possible confounding factors. In DCM-DM group, CSCT recovery ratio was also correlated with preoperative HbA1 level (R = - 0.55, p = 0.003). Furthermore, DM duration longer than 10 years and insulin dependence were risk factors for lower mJOA, CMCT and CSCT recoveries among all DCM-DM patients (t test, p < 0.05). CONCLUSIONS: DM may directly hinders spinal cord conduction recovery in DCM patients after surgery. Corticospinal tract impairments are similar between DCM and DCM-DM patients, but significantly worsened in chronic or insulin-dependent DM patients. The dorsal column is more sensitively affected in all DCM-DM patients. Deeper investigation into the mechanisms and neural regeneration strategies is needed.

Exercise combined with administration of adipose-derived stem cells ameliorates neuropathic pain after spinal cord injury.

Experimental studies have shown that exercise and human adipose-derived stem cells (ADSCs) play positive roles in spinal cord injury (SCI). However, whether ADSCs and/or exercise have a positive effect on SCI-induced neuropathic pain is still unclear. Thus, there is a need to explore the effects of exercise combined with administration of ADSCs on neuropathic pain after SCI. In this study, a thoracic 11 (T11) SCI contusion model was established in adult C57BL/6 mice. Exercise was initiated from 7 days post-injury and continued to 28 days post-injury, and approximately 1 × 105 ADSCs were transplanted into the T11 spinal cord lesion site immediately after SCI. Motor function and neuropathic pain-related behaviors were assessed weekly using the Basso Mouse Scale, von Frey filament test, Hargreaves method, and cold plate test. Histological studies (Eriochrome cyanine staining and immunohistochemistry) were performed at the end of the experiment (28 days post-injury). Exercise combined with administration of ADSCs partially improved early motor function (7, 14, and 21 days post-injury), mechanical allodynia, mechanical hypoalgesia, thermal hyperalgesia, and thermal hypoalgesia. Administration of ADSCs reduced white and gray matter loss at the lesion site. In addition, fewer microglia and astrocytes (as identified by expression of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, respectively) were present in the lumbar dorsal horn in the SCI + ADSCs and SCI + exercise + ADSCs groups compared with the sham group. Our findings suggest that exercise combined with administration of ADSCs is beneficial for the early recovery of motor function and could partially ameliorate SCI-induced neuropathic pain.

Application of electrophysiological measures in degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is one of the leading causes of progressive spinal cord dysfunction in the elderly. Early diagnosis and treatment of DCM are essential to avoid permanent disability. The pathophysiology of DCM includes chronic ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Electrophysiological studies including electromyography (EMG), nerve conduction study (NCS), motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) are useful in detecting the presymptomatic pathological changes of the spinal cord, and thus supplementing the early clinical and radiographic examinations in the management of DCM. Preoperatively, they are helpful in detecting DCM and ruling out other diseases, assessing the spinal cord compression level and severity, predicting short- and long-term prognosis, and thus deciding the treatment methods. Intra- and postoperatively, they are also useful in monitoring neurological function change during surgeries and disease progression during follow-up rehabilitation. Here, we reviewed articles from 1979 to 2021, and tried to provide a comprehensive, evidence-based review of electrophysiological examinations in DCM. With this review, we aim to equip spinal surgeons with the basic knowledge to diagnosis and treat DCM using ancillary electrophysiological tests.

Voluntary exercise ameliorates neuropathic pain by suppressing calcitonin gene-related peptide and ionized calcium-binding adapter molecule 1 overexpression in the lumbar dorsal horns in response to injury to the cervical spinal cord.

BACKGROUND: Neuropathic pain (NP) is a frequent finding in patients diagnosed with spinal cord injuries (SCIs). To improve our understanding of the maladaptive changes taking place in the lumbar spinal cord that can lead to the development of NP and to find alternative options to treat this condition, we aimed to investigate the effects of voluntary exercise on NP after SCI and to elucidate its potential mechanisms. METHODS: A rat model of post-SCI NP induced by compression of the posterior or lateral cervical spinal cord was used to evaluate the effects of voluntary exercise by measuring the bilateral withdrawal of the hind paws using the Von Frey filament and Hargreaves tests. The place escape/avoid paradigm was used to evaluate supraspinal pain processing and somatosensory evoked potentials (SEPs) were used to examine disturbances in proprioception. Locomotor function was evaluated using Basso, Beattie, and Bresnahan (BBB) scoring. Pathologic findings in hematoxylin and eosin-stained tissue and magnetic resonance imaging were used to evaluate the morphological changes after SCI. The lesion size within the cervical spinal cord was evaluated by staining with Eriochrome cyanine R. Quantitative polymerase chain reaction and immunohistochemistry were used to assess the expression of calcitonin gene-related peptide (CGRP) and ionized calcium-binding adapter molecule 1 (Iba-1) in the lumbar dorsal horns. RESULTS: All injured rats developed mechanical hypersensitivity, hyposensitivity, and thermal hyperalgesia in the contralateral hind paws at 1 week post-injury. Rats that underwent lateral compression injury developed NP in the ipsilateral hind paws 1 week later than rats with a posterior compression injury. Our findings revealed that voluntary exercise ameliorated mechanical allodynia and thermal hyperalgesia, and significantly improved proprioception as measured by SEP, but had no impact on mechanical hypoalgesia or motor recovery and provided no significant neuroprotection after recovery from an acute SCI. SCI-induced NP was accompanied by increased expression of CGRP and Iba-1 in the lumbar dorsal horn. These responses were reduced in rats that underwent voluntary exercise. CONCLUSIONS: Voluntary exercise ameliorates NP that develops in rats after compression injury. Increased expression of CGRP and Iba-1 in the lumbar dorsal horns of rats exhibiting symptoms of NP suggests that microglial activation might play a crucial role in its development. Collectively, voluntary exercise may be a promising therapeutic modality to treat NP that develops clinically in response to SCI.

Patients with degenerative cervical myelopathy exhibit neurophysiological improvement upon extension and flexion: a retrospective cohort study with a minimum 1-year follow-up.

BACKGROUND: Cervical extension and flexion are presumably harmful to patients with degenerative cervical myelopathy (DCM) because they worsen medullary compression visible on dynamic magnetic resonance imaging (MRI). Dynamic somatosensory evoked potentials (SSEPs) are an objective tool to measure the electrophysiological function of the spinal cord at different neck positions. In contrast to previous hypotheses, a considerable proportion of patients with DCM present improved SSEPs upon extension and flexion compared to a neutral position. METHODS: Patients with DCM who underwent preoperative dynamic SSEP examinations and subsequent decompression surgeries between 2015 and 2019 were retrospectively evaluated. We compared extension and flexion SSEPs with neutral SSEPs in each patient and classified them into extension-improved (EI) or extension-nonimproved (EN) and flexion-improved (FI) or flexion-nonimproved (FN) groups. Preoperative clinical evaluations, decompression surgical methods and one-year follow-up clinical data were recorded. Cervical spondylolisthesis and cervical alignment types were evaluated on plain cervical lateral radiographs. The number of stenotic segments, Mühle stenosis grade and disc degeneration stage of the most severe segment, and presence of ligamentum flavum hypertrophy and intramedullary T2 weighted imaging (T2WI) hyperintensity were evaluated on lateral and axial MRI. Data were compared between the EN and EN groups or FI and FN groups with T-tests, chi-square tests or Kruskal-Wallis tests. Prediction criteria were determined with logistic regression analyses. RESULTS: Forty-nine patients were included, and 9 (18.4%) and 11 (22.4%) showed improved extension and flexion SSEPs compared to their own neutral SSEPs, respectively. Interestingly, EI or FI patients had significantly better one-year postoperative mJOA recoveries than EN or FN patients (T-test, P < 0.001). Moreover, the disease duration (T-test, P = 0.024), involved segment number (Kruskal-Wallis test, P < 0.001), and cervical alignment type (chi-square test, P = 0.005) varied significantly between the EI and EN groups. The FI group presented a significantly higher Mühle stenosis grade than the FN group (Kruskal-Wallis test, P = 0.038). Furthermore, ≤ 2 involved segments and straight or sigmoid cervical alignment were significant criteria predicting improved extension SSEPs (probability: 85.7%), while Mühle stenosis Grade 3 and disease duration ≤6 months were significant criteria predicting improved flexion SSEPs (probability: 85.7%). CONCLUSIONS: Our findings provide evidence for neurophysiological improvement in patients with DCM at extension and flexion and its significance in predicting prognoses. Moreover, certain clinical and radiographic criteria may help predict neurophysiological improvement upon extension or flexion. TRIAL REGISTRATION: " [2020]151 ". Retrospectively registered on April 30, 2020.

Spinal Cord Parenchyma Vascular Redistribution Underlies Hemodynamic and Neurophysiological Changes at Dynamic Neck Positions in Cervical Spondylotic Myelopathy.

Cervical spondylotic myelopathy (CSM) is a degenerative condition of the spine that caused by static and dynamic compression of the spinal cord. However, the mechanisms of motor and somatosensory conduction, as well as pathophysiological changes at dynamic neck positions remain unclear. This study aims to investigate the interplay between neurophysiological and hemodynamic responses at dynamic neck positions in the CSM condition, and the pathological basis behind. We first demonstrated that CSM patients had more severe dynamic motor evoked potentials (DMEPs) deteriorations upon neck flexion than upon extension, while their dynamic somatosensory evoked potentials (DSSEPs) deteriorated to a similar degree upon extension and flexion. We therefore generated a CSM rat model which developed similar neurophysiological characteristics within a 4-week compression period. At 4 weeks-post-injury, these rats presented decreased spinal cord blood flow (SCBF) and oxygen saturation (SO2) at the compression site, especially upon cervical flexion. The dynamic change of DMEPs was significantly correlated with the change in SCBF from neutral to flexion, suggesting they were more sensitive to ischemia compared to DSSEPs. We further demonstrated significant vascular redistribution in the spinal cord parenchyma, caused by angiogenesis mainly concentrated in the anterior part of the compressed site. In addition, the comparative ratio of vascular densities at the anterior and posterior parts of the cord was significantly correlated with the perfusion decrease at neck flexion. This exploratory study revealed that the motor and somatosensory conductive functions of the cervical cord changed differently at dynamic neck positions in CSM conditions. Compared with somatosensory conduction, the motor conductive function of the cervical cord suffered more severe deteriorations upon cervical flexion, which could partly be attributed to its higher susceptibility to spinal cord ischemia. The uneven angiogenesis and vascular distribution in the spinal cord parenchyma might underlie the transient ischemia of the cord at flexion.

Corrigendum: Pathophysiological Changes and the Role of Notch-1 Activation After Decompression in a Compressive Spinal Cord Injury Rat Model.

[This corrects the article DOI: 10.3389/fnins.2021.579431.].

Pathophysiological Changes and the Role of Notch-1 Activation After Decompression in a Compressive Spinal Cord Injury Rat Model.

Surgical decompression is the primary treatment for cervical spondylotic myelopathy (CSM) patients with compressive spinal cord injury (CSCI). However, the prognosis of patients with CSCI varies, and the pathophysiological changes following decompression remain poor. This study aimed to investigate the pathophysiological changes and the role of Notch-1 activation after decompression in a rat CSCI model. Surgical decompression was conducted at 1 week post-injury (wpi). DAPT was intraperitoneally injected to down-regulate Notch-1 expression. Basso, Beattie, and Bresnahan scores and an inclined plane test were used to evaluate the motor function recovery. Hematoxylin and eosin staining was performed to assess pathophysiological changes, while hypoxia-inducible factor 1 alpha, vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), matrix metalloproteinase (MMP)-9, MMP-2, Notch-1, and Hes-1 expression in the spinal cord were examined by immunohistochemical analysis or quantitative PCR. The results show that early decompression can partially promote motor function recovery. Improvements in structural and cellular damage and hypoxic levels were also observed in the decompressed spinal cord. Moreover, decompression resulted in increased VEGF and vWF expression, but decreased MMP-9 and MMP-2 expression at 3 wpi. Expression levels of Notch-1 and its downstream gene Hes-1 were increased after decompression, and the inhibition of Notch-1 significantly reduced the decompression-induced motor function recovery. This exploratory study revealed preliminary pathophysiological changes in the compressed and decompressed rat spinal cord. Furthermore, we confirmed that early surgical decompression partially promotes motor function recovery may via activation of the Notch-1 signaling pathway after CSCI. These results could provide new insights for the development of drug therapy to enhance recovery following surgery.

Simultaneous incorporation of PTH(1-34) and nano-hydroxyapatite into Chitosan/Alginate Hydrogels for efficient bone regeneration.

Tissue regeneration based on the utilization of artificial soft materials is considered a promising treatment for bone-related diseases. Here, we report cranial bone regeneration promoted by hydrogels that contain parathyroid hormone (PTH) peptide PTH(1-34) and nano-hydroxyapatite (nHAP). A combination of the positively charged natural polymer chitosan (CS) and negatively charged sodium alginate led to the formation of hydrogels with porous structures, as shown by scanning electron microscopy. Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of nHAP and PTH(1-34). In vitro experiments showed that the hydrogel containing nHAP and PTH(1-34) exhibited strong biocompatibility and facilitated osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) via the Notch signaling pathway, as shown by the upregulated expression of osteogenic-related proteins. We found that increasing the content of PTH(1-34) in the hydrogels resulted in enhanced osteogenic differentiation of BMSCs. Implantation of the complex hydrogel into a rat cranial defect model led to efficient bone regeneration compared to the rats treated with the hydrogel alone or with nHAP, indicating the simultaneous therapeutic effect of nHAP and PTH during the treatment process. Both the in vitro and in vivo results demonstrated that simultaneously incorporating nHAP and PTH into hydrogels shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future.

Magnetic resonance imaging and dynamic X-ray's correlations with dynamic electrophysiological findings in cervical spondylotic myelopathy: a retrospective cohort study.

BACKGROUND: Dynamic somatosensory evoked potentials (DSSEP) can be used to disclose abnormalities of ascending sensory pathways at dynamic positions and diagnose cervical spondylotic myelopathy (CSM). However, radiographic tests including magnetic resonance imaging (MRI) and dynamic X-ray are used much more widely in the management of CSM. Our study aims to clarify the correlations between several radiographic parameters and the DSSEP results, and further determine their reliability with clinical data. METHODS: We retrospectively enrolled 38 CSM patients with surgical intervention. DSSEP tests were performed before surgery. Amplitude ratios of DSSEP N13 and N20 waves at extension and flexion were calculated and recorded as N13_E, N20_E, N13_F, N20_F, respectively. Baseline severity was evaluated with the modified Japanese Orthopedic Association (mJOA) score and the Nurick grades. Prognosis was evaluated based on the 2-year recovery rate. Sagittal diameter and transverse areas of the cord and canal were measured and the the compressive ratios at the compressed site (Compression_Ratio), central (Central_Ratio), and 1/4-lateral points (1/4-Lateral_Compression_Ratio), and spinal cord/Canal Area Ratio were calculated. The intramedullary T2 hyperintensity patterns (Ax-CCM types) were also collected from MRI axial images. Dynamic X-rays were used to test for segmental instability of the cervical spine. The correlations between radiologic findings, DSSEP data, and clinical assessments were investigated. RESULTS: We found that DSSEP N13_E and N13_F correlated with the Compression_Ratio, Central_Ratio, 1/4-Lateral_Compression_Ratio (Pearson, p < 0.05) and Ax-CCM types (ANOVA, p < 0.05) in MRI axial images and cervical segmental instability in dynamic X-ray (t-test, p < 0.05). Apart from the 1/4-Lateral_Compression_Ratio, these radiographic parameters above also correlated with the baseline clinical assessments (Spearman or ANOVA or t-test, p < 0.05) and postoperative recovery rate (Pearson or ANOVA or t-test, p < 0.05). CONCLUSIONS: We found that the preoperative Compression_Ratio, Central_Ratio and 1/4-Lateral_Compression_Ratio in MRI and cervical segmental instability in dynamic X-ray could reflect the dynamic neural dysfunction of the spinal cord. Different Ax-CCM types corresponded to different DSSEP results at extension and flexion, suggesting divergent pathophysiology. These radiographic parameters could help evaluate disease severity and predict postoperative prognosis.

LncRNA Xist Contributes to Endogenous Neurological Repair After Chronic Compressive Spinal Cord Injury by Promoting Angiogenesis Through the miR-32-5p/Notch-1 Axis.

Endogenous repair after chronic compressive spinal cord injury (CCSCI) is of great clinical interest. Ischemia-hypoxia-induced angiogenesis has been proposed to play an important role during this repair process. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are involved in the pathophysiological processes of various diseases. Here, we identified a lncRNA (Xist; X-inactive specific transcript) with upregulated expression in cervical spine lesions during endogenous neurological repair in CCSCI rats. Therapeutically, the introduction of Xist to rats increased neurological function in vivo as assayed using the Basso, Beattie, and Bresnahan (BBB) score and inclined plane test (IPT). We found that the introduction of Xist enhanced endogenous neurological repair by promoting angiogenesis and microvessel density after CCSCI, while depletion of Xist inhibited angiogenesis and cell sprouting and migration. Mechanistically, Xist promoted angiogenesis by sponging miR-32-5p and modulating Notch-1 expression both in vitro and in vivo. These findings suggest a role of the Xist/miR-32-5p/Notch-1 axis in endogenous repair and provide a potential molecular target for the treatment of ischemia-related central nervous system (CNS) diseases.

Regulatory Roles of Bone in Neurodegenerative Diseases.

Osteoporosis and neurodegenerative diseases are two kinds of common disorders of the elderly, which often co-occur. Previous studies have shown the skeletal and central nervous systems are closely related to pathophysiology. As the main structural scaffold of the body, the bone is also a reservoir for stem cells, a primary lymphoid organ, and an important endocrine organ. It can interact with the brain through various bone-derived cells, mostly the mesenchymal and hematopoietic stem cells (HSCs). The bone marrow is also a place for generating immune cells, which could greatly influence brain functions. Finally, the proteins secreted by bones (osteokines) also play important roles in the growth and function of the brain. This article reviews the latest research studying the impact of bone-derived cells, bone-controlled immune system, and bone-secreted proteins on the brain, and evaluates how these factors are implicated in the progress of neurodegenerative diseases and their potential use in the diagnosis and treatment of these diseases.