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Purpose We utilized the Fast Low Angle Shot (FLASH) sequence to document the sequential changes in cartilaginous (CEP) and bony end plate (BEP) to study the influence on disc degeneration (DD). Methods Routine MRI and FLASH sequences were used in 500 lumbar discs in 100 each of healthy volunteers (HV), low back pain patients treated conservatively (CG) and surgically (SG) to document CEP and BEP status, Pfirrmann Grade (PG) and various MRI parameters. Results The three groups were identical demographically but had a significantly different number of healthy discs ( p  < 0.01) and changes in CEP and BEP ( p  < 0.01), with patients having a higher severity of end plate changes and DD, even in asymptomatic discs. CEP abnormalities always appeared first, followed by a sequence of BEP defects of different severity, allowing the development of an ‘Integrated Total End Plate Score’ (I-TEPS). There was a good correlation between I-TEPS and PG, with a steep escalation of DD after a score of 7. A score of ≥  7 was also associated with higher surgical incidence in patients with both degenerated and herniated discs. The most significant influencing factors for surgery was a combination of I-TEPS  ≥  7 with herniation (OR7.7;p-0.00), smoking (OR4.63;p-0.02), and an I-TEPS  ≥  7 (OR3.37;p-0.04). Conclusion CEP changes identified by FLASH preceded BEP defects and DD. I-TEPS was superior to TEPS in identifying a subgroup of discs that had CEP abnormalities without BEP. An I-TEPS  ≥  7 had a significant correlation to the severity of DD, influenced variations in herniation and also surgical incidence.

By mediating voluntary muscle movement, vertebrate neuromuscular junctions (NMJ) play an extraordinarily important role in physiology. While the significance of the nerve-muscle connectivity was already conceived almost 2000 years back, the precise cell and molecular biology of the NMJ have been revealed in a series of fascinating research activities that started around 180 years ago and that continues. In all this time, NMJ research has led to fundamentally new concepts of cell biology, and has triggered groundbreaking advancements in technologies. This review tries to sketch major lines of thought and concepts on NMJ in their historical perspective, in particular with respect to anatomy, function, and molecular components. Furthermore, along these lines, it emphasizes the mutual benefit between science and technology, where one drives the other. Finally, we speculate on potential major future directions for studies on NMJ in these fields.

Motor endplates (MEPs) are the important interfaces between peripheral nerves and muscle fibers. Investigation of the spatial distribution of MEPs could help us better understand neuromuscular functional activities and improve the diagnosis and therapy of related diseases. Fluorescent α-bungarotoxin was injected to label the motor endplates in whole-mount skeletal muscles, and tissue optical clearing combined with light-sheet microscopy was used to investigate the spatial distribution of MEPs and in-muscle nerve branches in different skeletal muscles in wild-type and transgenic fluorescent mice. Electrophysiology was used to determine the relationship between the spatial distribution of MEPs and muscle function. The exact three-dimensional distribution of MEPs in whole skeletal muscles was first obtained. We found that the MEPs in the muscle were distributed in an organized pattern of lamella clusters, with no MEPs outside the lamella zone. Each MEP lamella was innervated by one independent in-muscle nerve branch and mediated an independent muscle subgroup contraction. Additionally, the MEPs changed along the lamella clusters after denervation and regained the initial pattern after reinnervation. The integrity and spatial distribution of MEPs could reflect the functional state of muscles. The signal absence of a certain MEP lamella could suggest a problem in certain part of the muscle. The MEP lamella clusters might be the basis of neuromuscular function, and the spatial distribution of MEPs could serve as a testbed for evaluating the functional status of muscle and the therapeutic targeting map related to MEPs.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to motor neuron dysfunction resulting in impairment of neuromuscular transmission. A2A adenosine receptors have already been considered as a potential therapeutical target for ALS but their neuromodulatory role at the neuromuscular junction in ALS remains to be clarified. In the present work, we evaluated the effects of A2A receptors on neuromuscular transmission of an animal model of ALS: SOD1(G93A) mice either in the pre-symptomatic (4-6 weeks old) or in the symptomatic (12-14 weeks old) stage. Electrophysiological experiments were performed obtaining intracellular recordings in Mg2+ paralyzed phrenic nerve-hemidiaphragm preparations. Endplate potentials (EPPs), quantal content (q. c.) of EPPs, miniature endplate potentials (MEPPs) and giant miniature endplate potential (GMEPPs) were recorded. In the pre-symptomatic phase of the disease (4-6 weeks old mice), the selective A2A receptor agonist, CGS 21680, significantly enhanced (p<0.05 Unpaired t-test) the mean amplitude and q.c. of EPPs, and the frequency of MEPPs and GMEPPs at SOD1(G93A) neuromuscular junctions, the effect being of higher magnitude (p<0.05, Unpaired t-test) than age-matched control littermates. On the contrary, in symptomatic mice (12-14 weeks old), CGS 21680 was devoid of effect on both the amplitude and q.c. of EPPs and the frequency of MEPPs and GMEPPs (p<0.05 Paired t-test). The results herein reported clearly document that at the neuromuscular junction of SOD1(G93A) mice there is an exacerbation of A2A receptor-mediated excitatory effects at the pre-symptomatic phase, whereas in the symptomatic phase A2A receptor activation is absent. The results thus suggest that A2A receptors function changes with ALS progression.

Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results in minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth is too slow. Heat shock protein 27 (Hsp27) is a regeneration-associated protein that accelerates axonal growth in vitro. Here, we have shown that it can also do this in mice after peripheral nerve injury. While rapid motor and sensory recovery occurred in mice after a sciatic nerve crush injury, there was little return of motor function after sciatic nerve transection, because of the delay in motor axons reaching their target. This was not due to a failure of axonal growth, because injured motor axons eventually fully re-extended into muscles and sensory function returned; rather, it resulted from a lack of motor end plate reinnervation. Tg mice expressing high levels of Hsp27 demonstrated enhanced restoration of motor function after nerve transection/resuture by enabling motor synapse reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve injuries, shorter wait times to decompression surgery led to improved functional recovery, and, while a return of sensation occurred in all patients, motor recovery was limited. Thus, absence of motor recovery after nerve damage may result from a failure of synapse reformation after prolonged denervation rather than a failure of axonal growth.

Objective To investigate the feasibility of ultra-short echo time (UTE) magnetic resonance imaging (MRI) in the assessment of cartilage endplate (CEP) damage and further evaluate the relationship between total endplate score (TEPS) and lumbar intervertebral disc (IVD) degeneration for chronic low back pain patients. Materials and methods IVD were measured in 35 patients using UTE imaging at 3T MR. Subtracted UTE images between short and long TEs were obtained to depict anatomy of CEP. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated to assess the image quality quantitatively. A new grading criterion for endplate damage evaluation was developed based on Rajasekaran.S grading system in this study. Two radiologists were employed to evaluate CEP and bony vertebral endplates (VEP) using this new grading criterion and assess TEPS, independently. Cohen’s kappa analysis was applied to evaluate the inter-observer agreement of endplate damage assessment between two radiologists, and the Kendall’s TAU-B analysis was employed to determine the relationship between TEPS and IVD degeneration evaluated with Pfirrmann grading. Results Well structural CEP was depicted on subtracted UTE images and confirmed by high SNR (33.06±2.92) and CNR values (9.4±2.08). Qualified subtracted UTE images were used by two radiologists to evaluate the degree of CEP and VEP damage. Excellent inter-observer agreement was confirmed by high value in Cohen’s kappa test (0.839, P < 0.001). Ensured by this, 138 endplates from 69 IVDs of 35 patients were classified into six grades based on the new grading criterion and TEPS of each endplate was calculated. In addition, the degeneration degree of IVDs were classified into five grades. Finally, using Kendall’s TAU-B analysis, significant relationship was obtained between endplate damage related TEPS and IVD degeneration (r = 0.864, P < 0.001). Conclusion Ensured by high image quality, UTE imaging might be considered an effective tool to assess CEP damage. Additionally, further calculated TEPS has shown strong positive association with IVD degeneration, suggesting that the severity of endplate damage is highly linked with the degree of IVD degeneration.

The formation of the neuromuscular synapse requires muscle-specific receptor kinase (MuSK) to orchestrate postsynaptic differentiation, including the clustering of receptors for the neurotransmitter acetylcholine. Upon innervation, neural agrin activates MuSK to establish the postsynaptic apparatus, although agrin-independent formation of neuromuscular synapses can also occur experimentally in the absence of neurotransmission. Dok-7, a MuSK-interacting cytoplasmic protein, is essential for MuSK activation in cultured myotubes; in particular, the Dok-7 phosphotyrosine-binding domain and its target in MuSK are indispensable. Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK.

Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures. A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors. During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81±8.60° postoperatively to 25.13±8.91° at the final follow-up which showed a statistically significant difference ( <0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values ( <0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc-endplate complex injury (OR=17.46, =0.003); local kyphosis angle correction (OR=1.84, <0.001); and vertebral height restoration (OR=1.15, =0.003) were risk factors for re-kyphosis. Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc-endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.

Intervertebral disc (IVD) degeneration is a multifactorial pathological process associated with low back pain, the leading cause of years lived in disability worldwide. Key characteristics of the pathological changes connected with degenerative disc disease (DDD) are the degradation of the extracellular matrix (ECM), apoptosis and senescence, as well as inflammation. The impact of nonphysiological mechanical stresses on IVD degeneration and inflammation, the mechanisms of mechanotransduction, and the role of mechanosensitive miRNAs are of increasing interest. As post-transcriptional regulators, miRNAs are known to affect the expression of 30% of protein-coding genes and numerous intracellular processes. The dysregulation of miRNAs is therefore associated with various pathologies, including degenerative diseases such as DDD. This review aims to give an overview of the current status of miRNA research in degenerative disc pathology, with a special focus on the involvement of miRNAs in ECM degradation, apoptosis, and inflammation, as well as mechanobiology.

We investigated the incidence and clinical features of cage subsidence after single-level lateral lumbar interbody fusion (LLIF). We studied a retrospective cohort of 59 patients (34 males, 25 females; mean age, 68.9 years) who received single-level LLIF. Patients were classified into subsidence and no-subsidence groups. Cage subsidence was defined as any violation of either endplate, classified using radiographs and computed tomography (CT) images. After one year, we compared patient characteristics, surgical parameters, radiological findings, pain scores, and fusion status. We also compared the Hounsfield unit (HU) endplate value obtained on CT preoperatively. Twenty patients (33.9%) had radiographic evidence of interbody cage subsidence. There were significant differences between the subsidence and no-subsidence groups in sex, cage height, fusion rate, and average HU value of both endplates (p < 0.05). There were no significant differences in age, height, weight, or body mass index. Moreover, there were no significant differences in global alignment and Numerical Rating Scale change in low back pain, leg pain, and numbness. Despite suggestions that patients with lower HU values might develop cage subsidence, our results showed that cage subsidence after single-level LLIF was not associated with low back pain, leg pain, or numbness one year post-operation.