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Sample records for cervical intervertebral disc

  1. MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine.

    PubMed

    Stolworthy, Dean K; Bowden, Anton E; Roeder, Beverly L; Robinson, Todd F; Holland, Jacob G; Christensen, S Loyd; Beatty, Amanda M; Bridgewater, Laura C; Eggett, Dennis L; Wendel, John D; Stieger-Vanegas, Susanne M; Taylor, Meredith D

    2015-12-01

    Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2-6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann-grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration.

  2. Higher risk for cervical herniated intervertebral disc in physicians

    PubMed Central

    Liu, Cheng; Huang, Chien-Cheng; Hsu, Chien-Chin; Lin, Hung-Jung; Guo, How-Ran; Su, Shih-Bin; Wang, Jhi-Joung; Weng, Shih-Feng

    2016-01-01

    Abstract There is no study about cervical herniated intervertebral disc (cervical HIVD) in physicians in the literature; therefore, we conceived a retrospective nationwide, population-based cohort study to elucidate the topic. We identified 26,038 physicians, 33,057 non-physician healthcare providers (HCPs), and identical numbers of non-HCP references (i.e., general population). All cohorts matched a 1:1 ratio with age and gender, and each were chosen from the Taiwan National Health Insurance Research Database (NHIRD). We compared cervical HIVD risk among physicians, nonphysician HCPs, and non-HCP references and performed a follow-up between 2007 and 2011. We also made comparisons among physician specialists. Both physicians and nonphysician HCPs had higher cervical HIVD risk than non-HCP references (odds ratio [OR]: 1.356; 95% confidence interval (CI): 1.162–1.582; OR: 1.383; 95% CI: 1.191–1.605, respectively). There was no significant difference of cervical HIVD risk between physicians and nonphysician HCPs. In the comparison among physician specialists, orthopedists had a higher cervical HIVD risk than other specialists, but the difference was not statistically significant (adjusted OR: 1.547; 95% CI: 0.782–3.061). Physicians are at higher cervical HIVD risk than the general population. Because unknown confounders could exist, further prospective studies are needed to identify possible causation. PMID:27741118

  3. Qualitative and quantitative assessment of degeneration of cervical intervertebral discs and facet joints.

    PubMed

    Walraevens, Joris; Liu, Baoge; Meersschaert, Joke; Demaerel, Philippe; Delye, Hans; Depreitere, Bart; Vander Sloten, Jos; Goffin, Jan

    2009-03-01

    Degeneration of intervertebral discs and facet joints is one of the most frequently encountered spinal disorders. In order to describe and quantify degeneration and evaluate a possible relationship between degeneration and biomechanical parameters, e.g., the intervertebral range of motion and intradiscal pressure, a scoring system for degeneration is mandatory. However, few scoring systems for the assessment of degeneration of the cervical spine exist. Therefore, two separate objective scoring systems to qualitatively and quantitatively assess the degree of cervical intervertebral disc and facet joint degeneration were developed and validated. The scoring system for cervical disc degeneration consists of three variables which are individually scored on neutral lateral radiographs: "height loss" (0-4 points), "anterior osteophytes" (0-3 points) and "endplate sclerosis" (0-2 points). The scoring system for facet joint degeneration consists of four variables which are individually scored on neutral computed tomography scans: "hypertrophy" (0-2 points), "osteophytes" (0-1 point), "irregularity" on the articular surface (0-1 point) and "joint space narrowing" (0-1 point). Each variable contributes with varying importance to the overall degeneration score (max 9 points for the scoring system of cervical disc degeneration and max 5 points for facet joint degeneration). Degeneration of 20 discs and facet joints of 20 patients was blindly assessed by four raters: two neurosurgeons (one senior and one junior) and two radiologists (one senior and one junior), firstly based on first subjective impression and secondly using the scoring systems. Measurement errors and inter- and intra-rater agreement were determined. The measurement error of the scoring system for cervical disc degeneration was 11.1 versus 17.9% of the subjective impression results. This scoring system showed excellent intra-rater agreement (ICC = 0.86, 0.75-0.93) and excellent inter-rater agreement (ICC = 0

  4. Correlation between T2∗ (T2 star) relaxation time and cervical intervertebral disc degeneration

    PubMed Central

    Huang, Minghua; Guo, Yong; Ye, Qiong; Chen, Lei; Zhou, Kai; Wang, Qingjun; Shao, Lixin; Shi, Qinglei; Chen, Chun

    2016-01-01

    Abstract Purpose: To demonstrate the potential benefits of T2∗ relaxation time of intervertebral discs (IVDs) regarding the detection and grading of degenerative disc disease using 3.0-T magnetic resonance imaging (MRI) in a clinical setting. Materials and Methods: Cervical sagittal T2-weighted, T2∗ relaxation MRI was performed at 3.0-T in 61 subjects, covering discs C2–3 to C6–7. All discs were morphologically assessed based on the Pfirrmann grade, and regions of interests (ROIs) were drawn over the T2∗ mapping. Receiver operating characteristic (ROC) analysis was performed among grades to determine the cut-off values. Results: Cervical intervertebral discs (IVDs) of patients were commonly determined to be at Pfirrmann grades III to V. The nucleus pulposus (NP) values did not differ significantly between sexes at the same anatomic level (P > 0.05). In the NP, the T2∗ values tended to decrease with increasing grade (P < 0.000), and a significant difference was found in the T2 values between grades I to V (P < 0.05). T2∗ values based on disc degeneration level classification were as follows: grade I (>30 milliseconds), grade II (24.55–29.99 milliseconds), grade III (21.65–24.54 milliseconds), grade IV (18.35–21.64 milliseconds), and grade V (<18.34 milliseconds). Conclusion: Our standardized method of region-specific quantitative T2∗ relaxation time evaluation seems capable of characterizing different degrees of disc degeneration quantitatively. The T2∗ values obtained in these cervical IVDs may serve as baseline values for future T2∗ measurements in both healthy and degenerated cervical discs. PMID:27893652

  5. Cervical intervertebral disc herniation treatment via radiofrequency combined with low-dose collagenase injection into the disc interior using an anterior cervical approach

    PubMed Central

    Wang, Zhi-Jian; Zhu, Meng-Ye; Liu, Xiao-Jian; Zhang, Xue-Xue; Zhang, Da-Ying; Wei, Jian-Mei

    2016-01-01

    Abstract This study aimed to determine the therapeutic effect of radiofrequency combined with low-dose collagenase injected into the disc interior via an anterior cervical approach for cervical intervertebral disc herniation. Forty-three patients (26–62-year old; male/female ratio: 31/12) with cervical intervertebral disc herniation received radiofrequency combined with 60 to 100 U of collagenase, injected via an anterior cervical approach. The degree of nerve function was assessed using the current Japanese Orthopaedic Association (JOA) scoring system at 3 and 12 months postoperation. A visual analogue scale (VAS) was used to evaluate the degree of pain preoperation and 7 days postoperation. The preoperative and 3 month postoperative protrusion areas were measured and compared via magnetic resonance imaging (MRI) and picture archiving and communication systems (PACS). Compared with the preoperative pain scores, the 7-day postoperative pain was significantly reduced (P <0.01). The excellent and good rates of nerve function amelioration were 93.0% and 90.7% at 3 and 12 months postoperation, respectively, which was not significantly different. Twenty-seven cases exhibited a significantly reduced protrusion area (P <0.01) at 3 months postoperation. No serious side effects were noted. To our knowledge, this is the first study to demonstrate that the use of radiofrequency combined with low-dose collagenase injection into the disc interior via an anterior cervical approach is effective and safe for the treatment of cervical intervertebral disc herniation. PMID:27336892

  6. Study of the influence of degenerative intervertebral disc changes on the deformation behavior of the cervical spine segment in flexion

    NASA Astrophysics Data System (ADS)

    Kolmakova, Tatyana V.

    2016-11-01

    The paper describes the model of the cervical spine segment (C3-C4) and the calculation results of the deformation behavior of the segment under degenerative changes of the intervertebral disc. The segment model was built based on the experimental literature data taking into account the presence of the cortical and cancellous bone tissue of vertebral bodies. The calculation results show that degenerative changes of the intervertebral disc cause the immobility of the C3 vertebra at flexion.

  7. Cervical intervertebral disc protrusion in an RAAF F-111C pilot: a case report.

    PubMed

    Newman, D G

    1996-04-01

    This case report describes a serious cervical spine injury occurring in an F-111 pilot of the RAAF. The pilot developed a significant cervical intervertebral disc protrusion with severe, progressive neurological signs and symptoms in his right arm for a period of 4 mo. Multiple investigations including MRI and myelography established the site of the lesion as C6/7. He eventually responded to bed rest and made a complete recovery. The aeromedical disposition of this aviator and the roles of different treatment modalities in the aviation environment are discussed. The need for more research into +Gz-related neck injuries and the requirement for preventive strategies to protect the cervical spines of high performance pilots are also highlighted.

  8. EVALUATION OF TERMINAL VERTEBRAL PLATE ON CERVICAL SPINE AT DIFFERENT AGE GROUPS AND ITS CORRELATION WITH INTERVERTEBRAL DISC THICKNESS

    PubMed Central

    Luiz Vieira, Juliano Silveira; da Silva Herrero, Carlos Fernando Pereira; Porto, Maximiliano Aguiar; Nogueira Barbosa, Marcello Henrique; Garcia, Sérgio Britto; Zambelli Ramalho, Leandra Náira; Aparecido Defino, Helton Luiz

    2015-01-01

    To evaluate, by means of histomorphometry, terminal vertebral plate thickness, intervertebral disc thickness and its correlation on different age groups, seeking to identify its correlation. Methods: C4-C5 and C5-C6 cervical segments removed from human cadavers of both genders were assessed and divided into five groups of 10-year age intervals, from 21 years old. TVP and intervertebral disc thickness evaluation was made by means of histomorphometry of histological slides stained with hematoxylin and eosyn. Lower C4 TVP, upper C5 TVP, and upper C6 TVP de were compared between each other and to the interposed intervertebral disc thickness between relevant TVP. Results: The thickness of terminal vertebral plates adjacent to the same ID did not show statistic differences. However, the comparison of upper and lower vertebral plates thickness on the same cervical vertebra (C5), showed statistical difference on all age groups studied. We found a statistical correlation coefficient above 80% between terminal vertebral plate and adjacent intervertebral disc, with a proportional thickness reduction of both structures on the different cervical levels studied, and also on the different age groups assessed. Conclusion: Terminal vertebral plate shows a morphologic correlation with the intervertebral disc next to it, and does not show correlation with the terminal vertebral plate on the same vertebra. PMID:26998448

  9. Effects of Ge Gen Decoction on PGE2 content and COX activity in the degenarated cervical intervertebral discs of rats.

    PubMed

    Jun, Zhou; Fang, Suping; Huo, Hairu; Qi, Yun; Guo, Shuying; Jiang, Tingliang; Shi, Qi

    2005-09-01

    After the rat model of cervical spondylosis was developed for 6 months, the PGE2 content and COX activity in the cervical intervertebral discs were determined respectively by radioimmunoassay and catalytic activity assay. The results indicated that the PGE2 content and COX activity in the model rat increased significantly, and that Ge Gen Decoction could down-regulate the PGE2 content and inhibit COX activity. This is possibly one of the mechanisms of Ge Gen Decoction for treating cervical spondylosis.

  10. Ranges of Cervical Intervertebral Disc Deformation during an In-Vivo Dynamic Flexion-Extension of the Neck.

    PubMed

    Yu, Yan; Mao, Haiqing; Li, Jing-Sheng; Tsai, Tsung-Yuan; Cheng, Liming; Wood, Kirkham B; Li, Guoan; Cha, Thomas D

    2017-03-23

    While abnormal loading is widely believed to cause cervical spine disc diseases, in-vivo cervical disc deformation during dynamic neck motion has not been well delineated. This study investigated the range of cervical disc deformation during an in-vivo functional flexion-extension of the neck. Ten asymptomatic human subjects were tested using a combined dual fluoroscopic imaging system and MRI based 3D modeling technique. Overall disc deformation was determined using the changes of the space geometry between upper and lower endplates of each intervertebral segment (C3/4, C4/5, C5/6 and C6/7). Five points (anterior, center, posterior, left and right) of each disc were analyzed to examine the disc deformation distributions. The data indicated that between the functional maximum flexion and extension of the neck, the anterior points of the discs experienced large changes of distraction/compression deformation and shear deformation. The higher level discs experienced higher ranges of disc deformation. No significant difference was found in deformation ranges at posterior points of all discs. The data indicated that the range of disc deformation is disc level dependent and the anterior region experienced larger changes of deformation than the center and posterior regions, except for the C6/7 disc. The data obtained from this study could serve as baseline knowledge for the understanding of the cervical spine disc biomechanics and for investigation of the biomechanical etiology of disc diseases. These data could also provide insights for development of motion preservation surgeries for cervical spine.

  11. Viscoelastic finite element analysis of the cervical intervertebral discs in conjunction with a multi-body dynamic model of the human head and neck.

    PubMed

    Esat, V; Acar, M

    2009-02-01

    This article presents the effects of the frontal and rear-end impact loadings on the cervical spine components by using a multi-body dynamic model of the head and neck, and a viscoelastic finite element (FE) model of the six cervical intervertebral discs. A three-dimensional multi-body model of the human head and neck is used to simulate 15 g frontal and 8.5 g rear-end impacts. The load history at each intervertebral joint from the predictions of the multi-body model is used as dynamic loading boundary conditions for the FE model of the intervertebral discs. The results from the multi-body model simulations, such as the intervertebral disc loadings in the form of compressive, tensile, and shear forces and moments, and from the FE analysis such as the von Mises stresses in the intervertebral discs are analysed. This study shows that the proposed approach that uses dynamic loading conditions from the multi-body model as input to the FE model has the potential to investigate the kinetics and the kinematics of the cervical spine and its components together with the biomechanical response of the intervertebral discs under the complex dynamic loading history.

  12. Clinical and magnetic resonance imaging features of compressive cervical myelopathy with traumatic intervertebral disc herniation in cynomolgus macaque (Macaca fascicularis)

    PubMed Central

    Choi, Yun-Jung; Park, Hye-Jin; Sohn, Chul-Ho; Jung, Kyeong Cheon; Park, Seong Hoe

    2016-01-01

    Intervertebral disc herniation (IVDH) with nucleus pulposus extrusion, traumatic or not, is a devastating clinical condition accompanied by neurological problems. Here we report a cynomolgus macaque suffering from acute and progressive neurological dysfunction by a blunt trauma due to neck collar, an animal handling device. Tetraplegia, urinary incontinence, decreased proprioception, and imperception of pain were shown on physical and neurological examinations. MRI sagittal T2 weighted sequences revealed an extensive protrusion of disc material between C2 and C3 cervical vertebra, and this protrusion resulted in central stenosis of the spinal cord. Histopathologic findings showed a large number of inflammatory cells infiltrated at sites of spinal cord injury (SCI). This case is the first report of compressive cervical SCI caused by IVDH associated with blunt trauma. PMID:28053621

  13. Clinical and magnetic resonance imaging features of compressive cervical myelopathy with traumatic intervertebral disc herniation in cynomolgus macaque (Macaca fascicularis).

    PubMed

    Choi, Yun-Jung; Park, Hye-Jin; Sohn, Chul-Ho; Jung, Kyeong Cheon; Park, Seong Hoe; Lee, Jae-Il

    2016-12-01

    Intervertebral disc herniation (IVDH) with nucleus pulposus extrusion, traumatic or not, is a devastating clinical condition accompanied by neurological problems. Here we report a cynomolgus macaque suffering from acute and progressive neurological dysfunction by a blunt trauma due to neck collar, an animal handling device. Tetraplegia, urinary incontinence, decreased proprioception, and imperception of pain were shown on physical and neurological examinations. MRI sagittal T2 weighted sequences revealed an extensive protrusion of disc material between C2 and C3 cervical vertebra, and this protrusion resulted in central stenosis of the spinal cord. Histopathologic findings showed a large number of inflammatory cells infiltrated at sites of spinal cord injury (SCI). This case is the first report of compressive cervical SCI caused by IVDH associated with blunt trauma.

  14. Reliable Magnetic Resonance Imaging Based Grading System for Cervical Intervertebral Disc Degeneration

    PubMed Central

    Chen, Antonia F.; Kang, James D.; Lee, Joon Y.

    2016-01-01

    Study Design Observational. Purpose To develop a simple and comprehensive grading system for cervical discs that precisely, consistently and meaningfully presents radiologic and morphologic data. Overview of Literature The Thompson grading system is commonly used to classify the severity of degenerative lumbar discs on magnetic resonance imaging (MRI). Inherent differences in the morphological and physiological characteristics of cervical discs have hindered development of precise classification systems. Other grading systems have been developed for degenerating cervical discs, but their versatility and feasibility in the clinical setting is suboptimal. Methods MRIs of 46 human cervical discs were de-identified and displayed in PowerPoint format. Each slide depicted a single disc with a normal (grade 0) disc displayed in the top right corner for reference. The presentation was given to 25 physicians comprising attending spine surgeons, spine fellows, orthopaedic residents, and two attending musculoskeletal radiologists. The grading system included Grade 0 (normal height compared to C2–3, mid cleft still visible), grade 1 (dark disc, normal height), grade 2 (collapsed disc, few osteophytes), and grade 3 (collapsed disc, many osteophytes). The ease of use of the system was gauged in the participants and the interobserver reliability was calculated. Results The intraclass correlation coefficient for interobserver reliability was 0.87, and 0.94 for intraobserver reliability, indicating excellent reliability. Ninety-five percent and 85 percent of the clinicians judged the grading system to be clinically feasible and useful in daily practice, respectively. Conclusions The grading system is easy to use, has excellent reliability, and can be used for precise and consistent clinician communication. PMID:26949461

  15. Mechanotransduction in intervertebral discs

    PubMed Central

    Tsai, Tsung-Ting; Cheng, Chao-Min; Chen, Chien-Fu; Lai, Po-Liang

    2014-01-01

    Mechanotransduction plays a critical role in intracellular functioning—it allows cells to translate external physical forces into internal biochemical activities, thereby affecting processes ranging from proliferation and apoptosis to gene expression and protein synthesis in a complex web of interactions and reactions. Accordingly, aberrant mechanotransduction can either lead to, or be a result of, a variety of diseases or degenerative states. In this review, we provide an overview of mechanotransduction in the context of intervertebral discs, with a focus on the latest methods of investigating mechanotransduction and the most recent findings regarding the means and effects of mechanotransduction in healthy and degenerative discs. We also provide some discussion of potential directions for future research and treatments. PMID:25267492

  16. A 20-year-old female with Hirayama disease complicated with dysplasia of the cervical vertebrae and degeneration of intervertebral discs

    PubMed Central

    Hashimoto, Masaya; Yoshioka, Masayuki; Sakimoto, Yoshihiro; Suzuki, Masahiko

    2012-01-01

    A 20-year-old female patient was presented with a 1-year history of progressive weakness of the left hand. Examination on admission showed atrophy of the muscles of the left forearm, cold paralysis and minipolymyoclonus. MR images of the cervical cord showed anterior transfer of the cervical cord on anterior flexion and cervical cord compression at the site of cervical kyphosis, confirming the diagnosis of Hirayama disease. Many features of the present case are unusual: the patient is a female (who are rarely afflicted by this disease), with cervical kyphosis and a history of exercise involving cervical vertebral loading, suggesting a potential involvement of the latter two factors in the disease onset. The findings suggest that cervical vertebral dysplasia and intervertebral disc degeneration may influence cervical kyphosis, and be involved in the onset of Hirayama disease. PMID:23144342

  17. Development of Ultrasound to Measure In-vivo Dynamic Cervical Spine Intervertebral Disc Mechanics

    DTIC Science & Technology

    2014-01-01

    images of IVDs and dynamic vertebral motion in-vivo during simulated tasks relevant to acute and chronic cervical spine injury and disease. A semi...of cervical vertebrae. Dynamic IVD displacements of vertebrae C4-5 measured by US were consistent with direct measurements. For motion frequencies...We developed a diagnostic system that applies dynamic cyclic loads to cervical spine over a range of programmable frequencies and amplitudes that

  18. Intervertebral disc replacement. Experimental study.

    PubMed

    Kostuik, J P

    1997-04-01

    Arthrodesis of the lumbosacral spine, although satisfactory for a majority of patients, has long term sequelae in 30% of patients. This is particularly true for adjacent segment degeneration. Numerous attempts at providing a mobile motion segment have been made in the past. The current status of the development of dynamic intervertebral prosthesis, including biomechanical and clinical data have been presented. The relevant material properties of plastics, ceramics, and metal are presented with the conclusion that metals currently present with the greatest longevity without undue fatigue and wear as many as 100,000,000 cycles (40 years use) as an alternative to spinal fusion. An analysis of the kinematics of the motion segment have resulted, together with the material properties in the development of a dynamic intervertebral disc for use in the lumbar spine. The disc resembles a normal motion segment. In motion stiffness and center of rotation, wear debris development in 1/300 equivalent to that of a total hip prosthesis for the same given time. Safety features include immediate screw fixation to prevent displacement, a wedge elastic (spring) shape, and a bony porous ingrowth surface. The prosthesis is constructed of cobalt chromium and titanium with minimal corrosive properties on long term testing.

  19. Genetics Home Reference: intervertebral disc disease

    MedlinePlus

    ... link) National Institute of Neurological Disorders and Stroke: Low Back Pain Fact Sheet Educational Resources (8 links) American Association ... MalaCards: intervertebral disc disease Merck Manual Consumer Version: Low Back Pain Merck Manual Consumer Version: Neck Pain The Children's ...

  20. Pediatric intervertebral disc calcification: A no touch lesion.

    PubMed

    Garg, Monika; Kumar, Sanyal; Satija, Bhawna; Gupta, Rajat

    2012-01-01

    Intervertebral disc calcification (IVDC), though rare, remains an important differential of pediatric spinal pain. A 7-year-old boy presented with sudden-onset severe neck pain and restricted movements. There was no definite history of trauma or infection. Imaging of the cervical spine showed calcification of the intervertebral disc at C2-3 level, with significant posterior protrusion into the spinal canal causing compression of the cervical spinal cord. The child was kept on conservative management. The calcification and posterior protrusion showed near-complete resolution on 3-month follow-up. This case report emphasizes that childhood IVDC is a benign condition which commonly resolves spontaneously, without any surgical intervention and neurological sequelae.

  1. Roentgenographic measurement of lumbar intervertebral disc height.

    PubMed

    Andersson, G B; Schultz, A; Nathan, A; Irstam, L

    1981-01-01

    The influences of differences in both intervertebral motion segment orientations and in reader judgments on measurements of the apparent intervertebral disc heights in lateral roentgenographs of the lumbar spine were examined. Forty-nine roentgenographs were obtained of nine discs that were titled laterally up to +/- 10 degrees, and rotated longitudinally up to +/- 20 degrees. Three orthopaedic surgeons and three radiologists measured disc heights from five of these roentgenographs, all using the same measurement method. The differences in apparent height that resulted from the orientation changes and differences in judgments among the six readers were considerable, usually of the order of one half of the nominal disc height. The results show that, while roentgenographic measurements can be used to estimate disc height, accurate measurements cannot readily be made from routine roentgenographs, and the interpretation should always be cautious.

  2. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  3. Validation of Sodium MRI of Intervertebral Disc

    PubMed Central

    Wang, Chenyang; McArdle, Erin; Fenty, Matthew; Witschey, Walter; Elliott, Mark; Sochor, Matthew; Reddy, Ravinder; Borthakur, Arijitt

    2009-01-01

    Study Design This study demonstrated the diagnostic potential of sodium MRI for non-invasive quantification of PG in the intervertebral discs. Objective To determine the existence of a linear correlation between intervertebral disc [Na] measured from sodium MRI and [PG] measurement from DMMB assay. Summary of Background Data Previous studies have shown the possibility of quantifying [Na] in vivo using sodium MRI, however none has shown a direct linear correlation between [Na] measured from sodium MRI and [PG]. Methods 3D sodium MRI images of bovine discs were acquired and converted into [Na] maps. Samples were systematically removed from the discs for DMMB assay. The removal locations were photographically recorded and applied to the [Na] maps to extract the [Na] measurements for comparison. In vivo sodium MRI scans were also carried out on a pair of symptomatic and asymptomatic subjects. Results The linear regression fit of [Na] versus [PG] data yielded a significant linear correlation coefficient of 0.71. The in vivo sodium MRI image of the symptomatic subject showed significant [Na] decrease when compared to that of the asymptomatic subject. Conclusion Sodium MRI's specificity for PG in the intervertebral discs makes it a promising diagnostic tool for the earlier phase of disc degeneration. PMID:20147881

  4. Spontaneous lumbar intervertebral disc protrusion in cats: literature review and case presentations.

    PubMed

    Kathmann, I; Cizinauskas, S; Rytz, U; Lang, J; Jaggy, A

    2000-12-01

    Reports on intervertebral disc disease in cats are rare in the veterinary literature. It has been postulated that intervertebral disc protrusion is a frequent finding during necropsy in cats, without having any clinical relevance (King and Smith 1958, King & Smith 1960a, King & Smith 1960b). However, a total of six cases with disc protrusions and clinically significant neurological deficits have been reported over the past decade. (Heavner 1971, Seim & Nafe 1981, Gilmore 1983, Littlewood et al 1984, Sparkes & Skerry 1990, Bagley et al 1995). As in dogs, there are also two types of intervertebral disc disease in cats: Hansen's type I (extrusion), and type II (herniation). Cervical spinal cord involvement was more commonly recognised in cats than the lumbar or the thoraco lumbar area. Cats over 15 years were mainly affected (King & Smith 1958, King & Smith 1960a, King & Smith 1960b). We describe two cats with lumbar intervertebral disc protrusions. Emphasis is placed on differential diagnoses, treatment and follow-up.

  5. Propriospinal Myoclonus Induced by a Herniated Lumbar Intervertebral Disc at a Young Age: A Case Report

    PubMed Central

    Song, Kwan Su; Kim, Chang Hyun; Lee, Ho Kook

    2011-01-01

    The cause of propriospinal myoclonus (PSM) is idiopathic. Cervical trauma, ischemic myelopathy secondary to a spinal dural arteriovenous fistula, syringomyelia, Lyme neuroborreliosis, human immunodeficiency virus central nervous system infection, and cervical disc herniation can be the cause of PSM, but lumbar herniated intervertebral disc (HIVD) induced PSM has not been reported. We describe a patient who presented with PSM induced by HIVD and was treated with an epidural steroid injection using a transforaminal approach. PMID:26064150

  6. [Biology and mechanobiology of the intervertebral disc].

    PubMed

    González Martínez, Emilio; García-Cosamalón, José; Cosamalón-Gan, Iván; Esteban Blanco, Marta; García-Suarez, Olivia; Vega, José A

    2017-01-24

    The intervertebral disc (IVD) is noted for its low cell content, and being the largest avascular structure of human body. The low amount of cells in the disc have to adapt to an anaerobic metabolism with low oxygen pressure and acidic pH. Apart from surviving in an adverse microenvironment, they are exposed to a high level of mechanical stress. The biological adaptation of cells to acidosis and hyperosmolarity conditions are regulated by mechanoproteins, which are responsible for converting a mechanical signal into a cellular response, thus modifying its gene expression. Mechanobiology helps us to better understand the pathophysiology of IVD and its potential biological repair.

  7. Analysis of rabbit intervertebral disc physiology based on water metabolism. II. Changes in normal intervertebral discs under axial vibratory load

    SciTech Connect

    Hirano, N.; Tsuji, H.; Ohshima, H.; Kitano, S.; Itoh, T.; Sano, A.

    1988-11-01

    Metabolic changes induced by axial vibratory load to the spine were investigated based on water metabolism in normal intervertebral discs of rabbits with or without pentobarbital anesthesia. Tritiated water concentration in the intervertebral discs of unanesthetized rabbits was reduced remarkably by axial vibration for 30 minutes using the vibration machine developed for this study. Repeated vibratory load for 18 and 42 hours duration showed the recovery of /sup 3/H/sub 2/O concentration of the intervertebral disc without anesthesia. Computer simulation suggested a reduction of blood flow surrounding the intervertebral disc following the vibration stress. However, no reduction of the /sup 3/H/sub 2/O concentration in the intervertebral disc was noted under anesthesia. Emotional stress cannot be excluded as a factor in water metabolism in the intervertebral disc.

  8. Cervical disc hernia operations through posterior laminoforaminotomy

    PubMed Central

    Yolas, Coskun; Ozdemir, Nuriye Guzin; Okay, Hilmi Onder; Kanat, Ayhan; Senol, Mehmet; Atci, Ibrahim Burak; Yilmaz, Hakan; Coban, Mustafa Kemal; Yuksel, Mehmet Onur; Kahraman, Umit

    2016-01-01

    Objective: The most common used technique for posterolateral cervical disc herniations is anterior approach. However, posterior cervical laminotoforaminomy can provide excellent results in appropriately selected patients with foraminal stenosis in either soft disc prolapse or cervical spondylosis. The purpose of this study was to present the clinical outcomes following posterior laminoforaminotomy in patients with radiculopathy. Materials and Methods: We retrospectively evaluated 35 patients diagnosed with posterolateral cervical disc herniation and cervical spondylosis with foraminal stenosis causing radiculopathy operated by the posterior cervical keyhole laminoforaminotomy between the years 2010 and 2015. Results: The file records and the radiographic images of the 35 patients were assessed retrospectively. The mean age was 46.4 years (range: 34-66 years). Of the patients, 19 were males and 16 were females. In all of the patients, the neurologic deficit observed was radiculopathy. The posterolaterally localized disc herniations and the osteophytic structures were on the left side in 18 cases and on the right in 17 cases. In 10 of the patients, the disc level was at C5-6, in 18 at C6-7, in 2 at C3-4, in 2 at C4-5, in 1 at C7-T1, in 1 patient at both C5-6 and C6-7, and in 1 at both C4-5 and C5-6. In 14 of these 35 patients, both osteophytic structures and protruded disc herniation were present. Intervertebral foramen stenosis was present in all of the patients with osteophytes. Postoperatively, in 31 patients the complaints were relieved completely and four patients had complaints of neck pain and paresthesia radiating to the arm (the success of operation was 88.5%). On control examinations, there was no finding of instability or cervical kyphosis. Conclusion: Posterior cervical laminoforaminotomy is an alternative appropriate choice in both cervical soft disc herniations and cervical stenosis. PMID:27217655

  9. Intervertebral disc properties: challenges for biodevices.

    PubMed

    Costi, John J; Freeman, Brian J C; Elliott, Dawn M

    2011-05-01

    Intervertebral disc biodevices that employ motion-preservation strategies (e.g., nucleus replacement, total disc replacement and posterior stabilization devices) are currently in use or in development. However, their long-term performance is unknown and only a small number of randomized controlled trials have been conducted. In this article, we discuss the following biodevices: interbody cages, nuclear pulposus replacements, total disc replacements and posterior dynamic stabilization devices, as well as future biological treatments. These biodevices restore some function to the motion segment; however, contrary to expectations, the risk of adjacent-level degeneration does not appear to have been reduced. The short-term challenge is to replicate the complex biomechanical function of the motion segment (e.g., biphasic, viscoelastic behavior and nonlinearity) to improve the quality of motion and minimize adjacent level problems, while ensuring biodevice longevity for the younger, more active patient. Biological strategies for regeneration and repair of disc tissue are being developed and these offer exciting opportunities (and challenges) for the longer term. Responsible introduction and rigorous assessment of these new technologies are required. In this article, we will describe the properties of the disc, explore biodevices currently in use for the surgical treatment of low back pain (with an emphasis on lumbar total disc replacement) and discuss future directions for biological treatments. Finally, we will assess the challenges ahead for the next generation of biodevices designed to replace the disc.

  10. Decellularized allogeneic intervertebral disc: natural biomaterials for regenerating disc degeneration

    PubMed Central

    Hu, Zhijun; Chen, Kai; Shan, Zhi; Chen, Shuai; Wang, Jiying; Mo, Jian; Ma, Jianjun; Xu, Wenbing; Qin, An; Fan, Shunwu

    2016-01-01

    Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo. Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro. Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro. Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo. In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases. PMID:26933821

  11. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  12. Genetic Factors in Intervertebral Disc Degeneration

    PubMed Central

    Feng, Yi; Egan, Brian; Wang, Jinxi

    2016-01-01

    Low back pain (LBP) is a major cause of disability and imposes huge economic burdens on human society worldwide. Among many factors responsible for LBP, intervertebral disc degeneration (IDD) is the most common disorder and is a target for intervention. The etiology of IDD is complex and its mechanism is still not completely understood. Many factors such as aging, spine deformities and diseases, spine injuries, and genetic factors are involved in the pathogenesis of IDD. In this review, we will focus on the recent advances in studies on the most promising and extensively examined genetic factors associated with IDD in humans. A number of genetic defects have been correlated with structural and functional changes within the intervertebral disc (IVD), which may compromise the disc’s mechanical properties and metabolic activities. These genetic and proteomic studies have begun to shed light on the molecular basis of IDD, suggesting that genetic factors are important contributors to the onset and progression of IDD. By continuing to improve our understanding of the molecular mechanisms of IDD, specific early diagnosis and more effective treatments for this disabling disease will be possible in the future. PMID:27617275

  13. Infections of cervical disc space after dental extractions

    PubMed Central

    Feigenbaum, J. A.; Stern, W. E.

    1974-01-01

    Two patients with infections of the cervical intervertebral disc space after dental procedures carried out by the same oral surgeon exhibited similar clinical courses and radiographic appearances. Both had bacteriological confirmation of infection by needle aspiration and were treated with appropriate antibiotics and bracing of the neck. The presumed aetiology and the possible pathogenesis are described. Evidence suggests that the two infections were the result of needle injection of a contaminated solution, the organisms of which haematogenously lodged in the intervertebral discs in the cervical region. Lymph drainage from the gums and teeth is suggested as a possible route of inoculation. Images PMID:4449000

  14. Lumbar intervertebral disc degeneration and related factors in Korean firefighters

    PubMed Central

    Jang, Tae-Won; Ahn, Yeon-Soon; Byun, Junsu; Lee, Jong-In; Kim, Kun-Hyung; Kim, Youngki; Song, Han-Soo; Lee, Chul-Gab; Kwon, Young-Jun; Yoon, Jin-Ha; Jeong, Kyoungsook

    2016-01-01

    Objectives The job of firefighting can cause lumbar burden and low back pain. This study aimed to identify the association between age and lumbar intervertebral disc degeneration and whether the association differs between field and administrative (non-field) firefighters. Methods Subjects were selected using a stratified random sampling method. Firefighters were stratified by geographic area, gender, age and type of job. First, 25 fire stations were randomly sampled considering regional distribution. Then firefighters were stratified by gender, age and their job and randomly selected among the strata. A questionnaire survey and MRI scans were performed, and then four radiologists used Pfirrmann classification methods to determine the grade of lumbar intervertebral disc degeneration. Results Pfirrmann grade increased with lumbar intervertebral disc level. Analysis of covariance showed that age was significantly associated with lumbar intervertebral disc degeneration (p<0.05). The value of β (parameter estimate) was positive at all lumbar intervertebral disc levels and was higher in the field group than in the administrative group at each level. In logistic regression analysis, type of job was statistically significant only with regard to the L4–5 intervertebral disc (OR 3.498, 95% CI 1.241 to 9.860). Conclusions Lumbar intervertebral disc degeneration is associated with age, and field work such as firefighting, emergency and rescue may accelerate degeneration in the L4–5 intervertebral disc. The effects of field work on lumbar intervertebral disc degeneration were not clear in discs other than at the level L4–5. PMID:27354080

  15. Hybrid cervical disc arthroplasty.

    PubMed

    Tu, Tsung-Hsi; Wu, Jau-Ching; Cheng, Henrich; Mummaneni, Praveen V

    2017-01-01

    For patients with multilevel cervical stenosis at nonadjacent segments, one of the traditional approaches has included a multilevel fusion of the abnormal segments as well as the intervening normal segment. In this video we demonstrate an alternative treatment plan with tailored use of a combination of anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) with an intervening skipped level. The authors present the case of a 72-year-old woman with myeloradiculopathy and a large disc herniation with facet joint degeneration at C3-4 and bulging disc at C5-6. After nonoperative treatment failed, she underwent a single-level ACDF at C3-4 and single-level arthroplasty at C5-6, which successfully relieved her symptoms. No intervention was performed at the normal intervening C4-5 segment. By using ACDF combined with arthroplasty, the authors have avoided a 3-level fusion for this patient and maintained the range of motion of 2 disc levels. The video can be found here: https://youtu.be/OrxcPUBvqLk .

  16. Angiogenesis in the degeneration of the lumbar intervertebral disc

    PubMed Central

    David, Gh; Iencean, SM; Mohan, A

    2010-01-01

    The goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth factor and vascular endothelial growth factor level measurements, as elements in the process of appreciating the disc angiogenesis. Also, pre–surgery and post–surgery QOL has been measured, as well as the intensity of the pain syndrome. We have identified factors capable of stimulating vascular endothelial growth (VEGF, FGF–2) for the examined disc material, but histological examination did not show angiogenesis. The process of angiogenesis at the degenerated intervertebral disc level affects the patient's quality of life both pre and postoperatively, and may be a predictive factor for the post–operative results. Patients can prevent the appearance of angiogenesis type degenerative processes of the intervertebral disc by avoiding angiogenesis correlated factors (weight control, physical effort, and smoking). PMID:20968201

  17. Can Exercise Positively Influence the Intervertebral Disc?

    PubMed

    Belavý, Daniel L; Albracht, Kirsten; Bruggemann, Gert-Peter; Vergroesen, Pieter-Paul A; van Dieën, Jaap H

    2016-04-01

    To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a narrative review. The majority of the available data come from cell or whole-disc loading models and animal exercise models. However, some studies have examined the impact of specific sports on IVD degeneration in humans and acute exercise on disc size. Based on the data available in the literature, loading types that are likely beneficial to the IVD are dynamic, axial, at slow to moderate movement speeds, and of a magnitude experienced in walking and jogging. Static loading, torsional loading, flexion with compression, rapid loading, high-impact loading and explosive tasks are likely detrimental for the IVD. Reduced physical activity and disuse appear to be detrimental for the IVD. We also consider the impact of genetics and the likelihood of a 'critical period' for the effect of exercise in IVD development. The current review summarises the literature to increase awareness amongst exercise, rehabilitation and ergonomic professionals regarding IVD health and provides recommendations on future directions in research.

  18. Engineering alginate for intervertebral disc repair.

    PubMed

    Bron, Johannes L; Vonk, Lucienne A; Smit, Theodoor H; Koenderink, Gijsje H

    2011-10-01

    Alginate is frequently studied as a scaffold for intervertebral disc (IVD) repair, since it closely mimics mechanical and cell-adhesive properties of the nucleus pulposus (NP) of the IVD. The aim of this study was to assess the relation between alginate concentration and scaffold stiffness and find preparation conditions where the viscoelastic behaviour mimics that of the NP. In addition, we measured the effect of variations in scaffold stiffness on the expression of extracellular matrix molecules specific to the NP (proteoglycans and collagen) by native NP cells. We prepared sample discs of different concentrations of alginate (1%-6%) by two different methods, diffusion and in situ gelation. The stiffness increased with increasing alginate concentration, while the loss tangent (dissipative behaviour) remained constant. The diffusion samples were ten-fold stiffer than samples prepared by in situ gelation. Sample discs prepared from 2% alginate by diffusion closely matched the stiffness and loss tangent of the NP. The stiffness of all samples declined upon prolonged incubation in medium, especially for samples prepared by diffusion. The biosynthetic phenotype of native cells isolated from NPs was preserved in alginate matrices up to 4 weeks of culturing. Gene expression levels of extracellular matrix components were insensitive to alginate concentration and corresponding matrix stiffness, likely due to the poor adhesiveness of the cells to alginate. In conclusion, alginate can mimic the viscoelastic properties of the NP and preserve the biosynthetic phenotype of NP cells but certain limitations like long-term stability still have to be addressed.

  19. Material considerations for intervertebral disc replacement implants.

    PubMed

    Taksali, Sudeep; Grauer, Jonathan N; Vaccaro, Alexander R

    2004-01-01

    Cervical and lumbar disc replacements are being performed with increasing frequency. Much of the background for the development for these implants is drawn from the literature of other joint replacements that have been in evolution and use for decades. Important variables for the function and longevity of such disc arthroplasty implants are clearly defined by the material properties of the components used for their production. The most frequently considered materials are cobalt-chrome alloys, titanium alloys, stainless steels, polyethylene, polyurethane and ceramics. In addition to implant materials, the interfaces of such materials must be considered. The bearing surfaces of an implant, in particular, are at risk of wear and failure. Overall, successful, long-term total disc arthroplasty requires a thorough understanding of biomaterials and how they can be used to achieve their desired goals.

  20. Cervical Total Disc Arthroplasty

    PubMed Central

    Basho, Rahul; Hood, Kenneth A.

    2012-01-01

    Symptomatic adjacent segment degeneration of the cervical spine remains problematic for patients and surgeons alike. Despite advances in surgical techniques and instrumentation, the solution remains elusive. Spurred by the success of total joint arthroplasty in hips and knees, surgeons and industry have turned to motion preservation devices in the cervical spine. By preserving motion at the diseased level, the hope is that adjacent segment degeneration can be prevented. Multiple cervical disc arthroplasty devices have come onto the market and completed Food and Drug Administration Investigational Device Exemption trials. Though some of the early results demonstrate equivalency of arthroplasty to fusion, compelling evidence of benefits in terms of symptomatic adjacent segment degeneration are lacking. In addition, non-industry-sponsored studies indicate that these devices are equivalent to fusion in terms of adjacent segment degeneration. Longer-term studies will eventually provide the definitive answer. PMID:24353955

  1. Propionibacterium acnes, Coagulase-Negative Staphylococcus, and the “Biofilm-like” Intervertebral Disc

    PubMed Central

    Coscia, Michael F.; Denys, Gerald A.; Wack, Matthew F.

    2016-01-01

    Study Design. Patients scheduled for spinal surgery were screened prospectively for a microbial presence associated with intervertebral disc specimens. Inclusion was limited to patients requiring surgery for any of five conditions: study patients with cervical spine intervertebral herniation (IVH), lumbar spine IVH, lumbar spine discogenic pain, and control patients with idiopathic scoliosis/Scheurermann's kyphosis or trauma/neuromuscular deformity. Exclusion criteria included ongoing systemic infection, abnormal pre-operative white cell counts, documented or suspected spinal infection, or previous surgery to the involved disc. Objective. The aim of this study was to test for an association between the presence of a bacterial entity in operated discs and a diagnosis of pathologic disc disease. Summary of Background Data. An association has been described between microbial colonization and progressive intervertebral disc degeneration in 36 herniation patients undergoing microdiscectomies. A total of 19 patients had positive cultures on long-term incubation, with Propionibacterium acnes present in 84% of discs. Materials and Methods. Discs were harvested during surgery, using strict sterile technique. Each disc was divided, with half the sample sealed in a sterile, commercially prepared anaerobic culture transport container, and half fixed in formalin. Live specimens were cultured for bacteria at a university-affiliated laboratory in a blinded fashion. Fixed pathologic specimens were gram-stained and read by a board-certified pathologist. Results. A total of 169 intervertebral discs from 87 patients were evaluated (46 males, 41 females). Positive cultures were noted in 76 of 169 discs (45%), with 34 discs positive for P. acnes and 30 discs positive for Staphylococcus. No pathologic evidence was seen of microorganisms, acute or chronic inflammation, or infection. Pooling the IVH and discogenic pain patients and contrasting them with control patients showed a

  2. Paraplegia by acute cervical disc protrusion after lumbar spine surgery.

    PubMed

    Chen, Sheng-Huan; Hui, Yu-Ling; Yu, Chong-Ming; Niu, Chi-Chien; Lui, Ping-Wing

    2005-04-01

    Non-traumatic paraplegia caused by herniation of the cervical intervertebral disc is an uncommon postoperative complication. A patient with claudication and radiculopathy was scheduled for lumbar laminectomy due to spinal stenosis. Postoperatively, numbness below T6 was found in his both legs of the patient. MRI showed a protruded intervertebral disc between C6 and C7. Despite urgent disectomy, the patient's lower extremities remained paralyzed without significant improvement for 3 months. Loss of muscle support during general anesthesia, excessive neck extension during endotracheal intubation and positioning, as well as bucking and agitation are believed as triggering factors for the protrusion of the cervical disc. We suggest that a complete history taking and physical examination be accomplished in patients scheduled for lumbar spine surgery in order to exclude coexisting cervical spine disorders. In addition, skillful endotracheal intubation and careful neck positioning are mandatory for patients receiving surgery in the prone position.

  3. Cell therapy for the degenerating intervertebral disc.

    PubMed

    Tong, Wei; Lu, Zhouyu; Qin, Ling; Mauck, Robert L; Smith, Harvey E; Smith, Lachlan J; Malhotra, Neil R; Heyworth, Martin F; Caldera, Franklin; Enomoto-Iwamoto, Motomi; Zhang, Yejia

    2017-03-01

    Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy. The IVD progressively degenerates with age in humans, and strategies to repair the IVD depend on the stage of degeneration. Cell therapy and cell-based gene therapy aim to address moderate disc degeneration; advanced stage disease may require surgery. Studies involving autologous, allogeneic, and xenogeneic cells have all shown good survival of these cells in the IVD, confirming that the disc niche is an immunologically privileged site, permitting long-term survival of transplanted cells. All of the animal studies reviewed here reported some improvement in disc structure, and 2 studies showed attenuation of local inflammation. Among the 50 studies reviewed, 25 used some type of scaffold, and cell leakage is a consistently noted problem, though some studies showed reduced cell leakage. Hydrogel scaffolds may prevent cell leakage and provide biomechanical support until cells can become established matrix producers. However, these gels need to be optimized to prevent this leakage. Many animal models have been leveraged in this research space. Rabbit is the most frequently used model (28 of 50), followed by rat, pig, and dog. Sheep and goat IVDs resemble those of humans in size and in the absence of notochordal cells. Despite this advantage, there were only 2 sheep and 1 goat studies of 50 studies in this cohort. It is also unclear if a study in large animals is needed before clinical trials since

  4. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  5. Histological Identification of Propionibacterium acnes in Nonpyogenic Degenerated Intervertebral Discs

    PubMed Central

    Yuan, Ye; Zhou, Zezhu; Jiao, Yucheng; Zheng, Yuehuan; Lin, Yazhou; Xiao, Jiaqi

    2017-01-01

    Purpose. Low-virulence anaerobic bacteria, especially the Propionibacterium acnes (P. acnes), have been thought to be a new pathogeny for a series of disc diseases. However, until now, there has been no histological evidence to confirm this link. The purpose of this study was to confirm the presence of P. acnes in nonpyogenic intervertebral discs via histological observation. Method. Degenerated intervertebral discs were harvested from 76 patients with low back pain and/or sciatica but without any symptoms of discitis or spondylodiscitis. The samples were cultured under anaerobic conditions and then examined using 16S rDNA PCR to screen for P. acnes. Samples found to be positive for P. acnes were stained with hematoxylin-eosin (HE) and modified Brown-Brenn staining and observed under a microscope. Results. Here, 16 intervertebral discs were found to be positive for P. acnes via 16S rDNA PCR and the prevalence was 21.05% (16/76). Among them, 7 samples had visible microbes stained with HE and modified Brown-Brenn staining. Morphological examination showed the bacteria to be Gram-positive and rod-shaped, so they were considered P. acnes. Conclusion. P. acnes is capable of colonizing some degenerated intervertebral discs without causing discitis, and its presence could be further confirmed by histological evidence. Targeting these bacteria may be a promising therapy method for some disc diseases.

  6. Analysis of rabbit intervertebral disc physiology based on water metabolism. I. Factors influencing metabolism of the normal intervertebral discs

    SciTech Connect

    Hirano, N.; Tsuji, H.; Ohshima, H.; Kitano, S.; Sano, A.

    1988-11-01

    Basic factors influencing the metabolism of intervertebral discs of rabbits were quantitatively analyzed based on the water metabolism. The blood flow surrounding the intervertebral disc was calculated using pharmacokinetic concepts from the data obtained by time-related tritiated water distribution analyses. The blood flow was estimated as 0.056 (mg/min/mg tissue) in the anterior annulus, 0.106 in the posterior annulus, 0.120 in the lateral annulus, and 0.084 in the nucleus pulposus, respectively (Experiment 1). Water content and fixed charge density in the intervertebral disc fractions also were measured (Experiment 2). The cations and uncharged small solutes transported into the disc tissue ranged in descending order from nucleus pulposus, lateral annulus, posterior annulus, to anterior annulus. The authors also calculated theoretically the swelling pressure of the proteoglycan in the intervertebral disc fractions from the results of Experiment 2. It was concluded that swelling pressure was highest in the nucleus pulposus, and lowest in the anterior annulus. The water in the posterior annulus is less exchangeable than in the other disc tissue fractions.

  7. MECHANICAL DESIGN CRITERIA FOR INTERVERTEBRAL DISC TISSUE ENGINEERING

    PubMed Central

    Nerurkar, Nandan L.; Elliott, Dawn M.; Mauck, Robert L.

    2009-01-01

    Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviour, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying measures where functional equivalence was achieved, and others where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. PMID:20080239

  8. The effectiveness of percutaneous laser disc decompression for the prolapsed lumbar intervertebral disc

    NASA Astrophysics Data System (ADS)

    Mu, Ming Wei; Liu, Wei; Feng, Wei; Ma, Nan

    2009-07-01

    Objective: to investigate the role of associated factors in the effectiveness of laser treatment for prolapsed lumber intervertebral disc. Method: 302 prolapsed lumber intervertebral discs in 212 patients were treated with percutaneous laser disc decompression (PLDD). Patients were followed up by 12month, the associated factors which affecting the effectiveness of treatment, ie age, duration of illness were analyzed. Results: Punctual Success rate was 100%. After 12 month's follow up, 86% successful outcomes were obtained, in which 93% successful outcomes were obtained in patients less than 50 years old, 92% successful outcomes was obtained in the patients whose duration of illness less than 1 year.

  9. Accuracy of survey radiographic diagnosis of intervertebral disc protrusion in dogs.

    PubMed

    Lamb, C R; Nicholls, A; Targett, M; Mannion, P

    2002-01-01

    To assess the diagnostic accuracy of survey radiography for canine thoracolumbar intervertebral disc protrusion, survey radiographs (lateral and ventrodorsal) of 64 dogs with surgically-confirmed thoracolumbar intervertebral disc protrusion, 51 dogs with negative myelograms and 29 dogs with various spinal conditions other than disc protrusion were reviewed by three independent observers who were unaware of any clinical information. There were marked differences in observer performance for diagnosis of intervertebral disc protrusion, although there were no significant differences in intraobserver diagnostic accuracy for small vs. large dogs. Accuracy of observers for determining sites of intervertebral disc protrusion using survey radiography was in the range 51-61%. All observers had low accuracy for identification of second sites of intervertebral disc protrusion. The most useful radiographic sign, narrowed intervertebral space, had only moderate sensitivity (range 64-69%) and moderate predictive value (range 63-71%) for intervertebral disc protrusion. Vacuum phenomenon was an infrequent but accurate sign of intervertebral disc protrusion. Recognition of multiple radiographic signs of intervertebral disc protrusion at one site was associated with increased accuracy of diagnosis. No observer was accurate enough to justify attempting targeted surgical treatment of intervertebral disc protrusion without myelography.

  10. Molecular Mechanisms of Biological Aging in Intervertebral Discs

    PubMed Central

    Vo, Nam V.; Hartman, Robert A.; Patil, Prashanti R.; Risbud, Makarand V.; Kletsas, Dimitris; Iatridis, James C.; Hoyland, Judith A.; Le Maitre, Christine L.; Sowa, Gwendolyn A.; Kang, James D.

    2016-01-01

    Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age-associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age-related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. PMID:26890203

  11. Solute transport in intervertebral disc: experiments and finite element modeling.

    PubMed

    Das, D B; Welling, A; Urban, J P G; Boubriak, O A

    2009-04-01

    Loss of nutrient supply to the human intervertebral disc (IVD) cells is thought to be a major cause of disc degeneration in humans. To address this issue, transport of molecules of different size have been analyzed by a combination of experimental and modeling studies. Solute transport has been compared for steady-state and transient diffusion of several different solutes with molecular masses in the range 3-70 kDa, injected into parts of the disc where degeneration is thought most likely to occur first and into the blood supply to the disc. Diffusion coefficients of fluorescently tagged dextran molecules of different molecular weights have been measured in vitro using the concentration gradient technique in thin specimens of disc outer annulus and nucleus pulposus. Diffusion coefficients were found to decrease with molecular weight following a nonlinear relationship. Diffusion coefficients changed more rapidly for solutes with molecular masses less than 10 kDa. Although unrealistic or painful, solutes injected directly into the disc achieve the largest disc coverage with concentrations that would be high enough to be of practical use. Although more practical, solutes injected into the blood supply do not penetrate to the central regions of the disc and their concentrations dissipate more rapidly. Injection into the disc would be the best method to get drugs or growth factors to regions of degeneration in IVDs quickly; else concentrations of solute must be kept at a high value for several hours in the blood supply to the discs.

  12. Bryan total disc arthroplasty: a replacement disc for cervical disc disease

    PubMed Central

    Wenger, Markus; Markwalder, Thomas-Marc

    2010-01-01

    Total disc arthroplasty is a new option in the treatment of cervical degenerative disc disease. Several types of cervical disc prostheses currently challenge the gold-standard discectomy and fusion procedures. This review describes the Bryan Cervical Disc System and presents the Bryan prosthesis, its indications, surgical technique, complications, and outcomes, as given in the literature. PMID:22915917

  13. In vivo experimental study of hat type cervical intervertebral fusion cage (HCIFC).

    PubMed

    Gu, Yu-tong; Yao, Zhen-jun; Jia, Lian-shun; Qi, Jin; Wang, Jun

    2010-12-01

    The purpose of this study was to compare the characteristics of interbody fusion achieved using the hat type cervical intervertebral fusion cage (HCIFC) with those of an autologous tricortical iliac crest graft, Harms cage and the carbon cage in a goat cervical spine model. Thirty-two goats underwent C3-4 discectomy and fusion. They were subdivided into four groups of eight goats each: group 1, autologous tricortical iliac crest bone graft; group 2, Harms cage filled with autologous iliac crest graft; group 3, carbon cage filled with autologous iliac bone; and group 4, HCIFC filled with autologous iliac graft. Radiography was performed pre- and postoperatively and after one, two, four, eight and 12 weeks. At the same time points, disc space height, intervertebral angle, and lordosis angle were measured. After 12 weeks, the goats were killed and fusion sites were harvested. Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending to determine the stiffness and range of motion. All cervical fusion specimens underwent histomorphological analyses. One week after operation, the disc space height (DSH), intervertebral angle (IVA) and lordosis angle (LA) of HCIFC and carbon cage were statistically greater than those of autologous iliac bone graft and Harms cage. Significantly higher values for DSH, IVA and LA were shown in cage-treated goats than in those that received bone graft over a 12-week period. The stiffness of Harms cage in axial rotation and lateral bending were statistically greater than that of other groups. Radiographic and histomorphological evaluation showed better fusion results in the cage groups than in the autologous bone group. HCIFC can provide a good intervertebral distractability and sufficient biomechanical stability for cervical fusion.

  14. Disc in Flames: Roles of TNF-α and IL-1β in Intervertebral Disc Degeneration

    PubMed Central

    Johnson, Zariel I.; Schoepflin, Zachary R.; Choi, Hyowon; Shapiro, Irving M.; Risbud, Makarand V.

    2016-01-01

    The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc, incited by aging, traumatic insult, genetic predisposition, or other factors, is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, and compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current therapies are limited and often focused on symptomatic pain relief rather than curtailing the progression of the disease. Inflammatory processes, exacerbated by cytokines TNF-α and IL-1β are believed to be key mediators of disc degeneration and low back pain. In this review, we describe the contributions of TNF-α and IL-1β to changes seen during disc degeneration at the cellular and tissue level, new evidence suggesting a link between infection of the spine and low back pain, and the emerging therapeutic modalities aimed at combating these processes. PMID:26388614

  15. ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

    PubMed Central

    Yang, Minghui; Lan, Minghong; Liu, Chang; Zhang, Yang; Huang, Bo

    2017-01-01

    Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD. PMID:28392887

  16. Advancing the cellular and molecular therapy for intervertebral disc disease.

    PubMed

    Sakai, Daisuke; Grad, Sibylle

    2015-04-01

    The healthy intervertebral disc (IVD) fulfils the essential function of load absorption, while maintaining multi-axial flexibility of the spine. The interrelated tissues of the IVD, the annulus fibrosus, the nucleus pulposus, and the cartilaginous endplate, are characterised by their specific niche, implying avascularity, hypoxia, acidic environment, low nutrition, and low cellularity. Anabolic and catabolic factors balance a slow physiological turnover of extracellular matrix synthesis and breakdown. Deviations in mechanical load, nutrient supply, cellular activity, matrix composition and metabolism may initiate a cascade ultimately leading to tissue dehydration, fibrosis, nerve and vessel ingrowth, disc height loss and disc herniation. Spinal instability, inflammation and neural sensitisation are sources of back pain, a worldwide leading burden that is challenging to cure. In this review, advances in cell and molecular therapy, including mobilisation and activation of endogenous progenitor cells, progenitor cell homing, and targeted delivery of cells, genes, or bioactive factors are discussed.

  17. Lumbosacral Sagittal Alignment in Association to Intervertebral Disc Diseases

    PubMed Central

    Maleki, Farid; Meybodi, Ali Tayebi; Mahdavi, Ali; Saberi, Hooshang

    2014-01-01

    Study Design A cross-sectional case-control study was designed to compare the sagittal alignment of lumbosacral regions in two groups of patients suffering from low back pain, one with intervertebral disc pathologies and one without. Purpose To evaluate the correlation between lumbosacral sagittal alignment and disc degeneration. Overview of Literature Changes in lumbar lordosis and pelvic parameters in degenerative disc lesions have been assessed in few studies. Overall, patients with discopathy were shown to have lower lumbar lordosis and more vertical sacral profiles. Methods From patients with intractable low back pain undergoing lumbosacral magnetic resonance imaging, 50 subjects with disc degeneration and 50 controls with normal scans were consecutively enrolled. A method was defined with anterior tangent-lines going through anterior bodies of L1 and S1 to measure global lumbosacral angle, incorporating both lumbar lordosis and sacral slope. Global lumbosacral angle using the proposed method and lumbar lordosis using Cobb's method were measured in both groups. Results Lumbar lordosis based on Cobb's method was lower in group with discopathy (20°-67°; mean, 40.48°±9.89°) than control group (30°-62°; mean, 44.96°±7.68°), although it was not statistically significant. The proposed global lumbosacral angle in subject group (53°-103°; mean, 76.5°±11.018°) was less than control group (52°-101°; mean, 80.18°±9.95°), with the difference being statistically significant (p=0.002). Conclusions Patients with intervertebral disc lesions seem to have more straightened lumbosacral profiles, but it has not been proven which comes first: disc degeneration or changes in sagittal alignment. Finding an answer to this dilemma demands more comprehensive long-term prospective studies. PMID:25558325

  18. Mechanisms for mechanical damage in the intervertebral disc annulus fibrosus.

    PubMed

    Iatridis, J C James C; ap Gwynn, Iolo

    2004-08-01

    Intervertebral disc degeneration results in disorganization of the laminate structure of the annulus that may arise from mechanical microfailure. Failure mechanisms in the annulus were investigated using composite lamination theory and other analyses to calculate stresses in annulus layers, interlaminar shear stress, and the region of stress concentration around a fiber break. Scanning electron microscopy (SEM) was used to evaluate failure patterns in the annulus and evaluate novel structural features of the disc tissue. Stress concentrations in the annulus due to an isolated fiber break were localized to approximately 5 microm away from the break, and only considered a likely cause of annulus fibrosus failure (i.e., radial tears in the annulus) under extreme loading conditions or when collagen damage occurs over a relatively large region. Interlaminar shear stresses were calculated to be relatively large, to increase with layer thickness (as reported with degeneration), and were considered to be associated with propagation of circumferential tears in the annulus. SEM analysis of intervertebral disc annulus fibrosus tissue demonstrated a clear laminate structure, delamination, matrix cracking, and fiber failure. Novel structural features noted with SEM also included the presence of small tubules that appear to run along the length of collagen fibers in the annulus and a distinct collagenous structure representative of a pericellular matrix in the nucleus region.

  19. In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification

    PubMed Central

    Ohnishi, Takashi; Sudo, Hideki; Iwasaki, Koji; Tsujimoto, Takeru; Ito, Yoichi M.; Iwasaki, Norimasa

    2016-01-01

    Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region. PMID:27482708

  20. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  1. Material properties of bovine intervertebral discs across strain rates.

    PubMed

    Newell, Nicolas; Grigoriadis, Grigorios; Christou, Alexandros; Carpanen, Diagarajen; Masouros, Spyros D

    2017-01-01

    The intervertebral disc (IVD) is a complex structure responsible for distributing compressive loading to adjacent vertebrae and allowing the vertebral column to bend and twist. To study the mechanical behaviour of individual components of the IVD, it is common for specimens to be dissected away from their surrounding tissues for mechanical testing. However, disrupting the continuity of the IVD to obtain material properties of each component separately may result in erroneous values. In this study, an inverse finite element (FE) modelling optimisation algorithm has been used to obtain material properties of the IVD across strain rates, therefore bypassing the need to harvest individual samples of each component. Uniaxial compression was applied to ten fresh-frozen bovine intervertebral discs at strain rates of 10(-3)-1/s. The experimental data were fed into the inverse FE optimisation algorithm and each experiment was simulated using the subject specific FE model of the respective specimen. A sensitivity analysis revealed that the IVD's response was most dependent upon the Young's modulus (YM) of the fibre bundles and therefore this was chosen to be the parameter to optimise. Based on the obtained YM values for each test corresponding to a different strain rate (ε̇), the following relationship was derived:YM=35.5lnε̇+527.5. These properties can be used in finite element models of the IVD that aim to simulate spinal biomechanics across loading rates.

  2. Protective effect of ligustrazine on lumbar intervertebral disc degeneration of rats induced by prolonged upright posture.

    PubMed

    Liang, Qian-Qian; Ding, Dao-Fang; Xi, Zhi-Jie; Chen, Yan; Li, Chen-Guang; Liu, Shu-Fen; Lu, Sheng; Zhao, Yong-Jian; Shi, Qi; Wang, Yong-Jun

    2014-01-01

    Most chronic low back pain is the result of degeneration of the lumbar intervertebral disc. Ligustrazine, an alkaloid from Chuanxiong, reportedly is able to relieve pain, suppress inflammation, and treat osteoarthritis and it has the protective effect on cartilage and chondrocytes. Therefore, we asked whether ligustrazine could reduce intervertebral disc degeneration. To determine the effect of ligustrazine on disc degeneration, we applied a rat model. The intervertebral disc degeneration of the rats was induced by prolonged upright posture. We found that pretreatment with ligustrazine for 1 month recovered the structural distortion of the degenerative disc; inhibited the expression of type X collagen, matrix metalloproteinase (MMP)-13, and MMP3; upregulated type II collagen; and decreased IL-1 β , cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression. In conclusion, ligustrazine is a promising agent for treating lumbar intervertebral disc degeneration disease.

  3. The avian intervertebral disc arises from rostral sclerotome and lacks a nucleus pulposus: Implications for evolution of the vertebrate disc

    PubMed Central

    Bruggeman, Bradley J.; Maier, Jennifer A.; Mohiuddin, Yasmin S.; Powers, Rae; Lo, YinTing; Guimarães-Camboa, Nuno; Evans, Sylvia M.; Harfe, Brian D.

    2012-01-01

    Deterioration of the intervertebral discs is an unfortunate consequence of aging. The intervertebral disc in mammals is composed of three parts: a jelly-like center called the nucleus pulposus, the cartilaginous annulus fibrosus and anterior and posterior endplates that attach the discs to vertebrae. In order to understand the origin of the disc, we have investigated the intervertebral region of chickens. Surprisingly, our comparison of mouse and chicken discs revealed that chicken discs lack nuclei pulposi. In addition, the notochord, which in mice forms nuclei pulposi, was found to persist as a rod-like structure and express Shh throughout chicken embryogenesis. Our fate mapping data indicates that cells originating from the rostral half of each somite are responsible for forming the avian disc while cells in the caudal region of each somite form vertebrae. A histological analysis of mammalian and non-mammalian organisms suggests that nuclei pulposi are only present in mammals. PMID:22354863

  4. Biomechanical study of a hat type cervical intervertebral fusion cage.

    PubMed

    Gu, Yu-Tong; Jia, Lian-Shun; Chen, Tong-Yi

    2007-02-01

    The purpose of this study was to evaluate the biomechanical effect of a hat type cervical intervertebral fusion cage (HCIFC). In this in vitro biomechanical study, 48 goat cervical spines (C2-5) were tested in flexion, extension, axial rotation, and lateral bending with a nondestructive stiffness method using a nonconstrained testing apparatus, and three-dimensional displacement was measured. Autologous iliac bone and cervical spine intervertebral fusion cage were implanted according to manufacturers' information after complete discectomy (C3-4). Eight spines in each of the following groups were tested: intact, autologous iliac bone graft, Harms cage, SynCage C, carbon cage, and HCIFC. The mean apparent stiffness values were calculated from the corresponding load-displacement curves. Additionally, cage volume and volume-related stiffness were determined. The stiffness of the SynCage C was statistically greatest in all directions. After implantation of the HCIFC, flexion stiffness increased compared with that of the intact motion segment. There was no significant difference in stiffness between the HCIFC and carbon cage. The stiffness of the HCIFC was statistically higher than that of the Harms cage in axial rotation and significantly lower in flexion, extension, and lateral bending. Volume-related stiffness of all cages was higher than that of iliac bone graft. The Harms cage was highest in volume-related stiffness in all directions. The HCIFC can provide enough primary stability for cervical intervertebral fusion.

  5. Prognosis of intervertebral disc loss from diagnosis of degenerative disc disease

    NASA Astrophysics Data System (ADS)

    Li, S.; Lin, A.; Tay, K.; Romano, W.; Osman, Said

    2015-03-01

    Degenerative Disc Disease (DDD) is one of the most common causes of low back pain, and is a major factor in limiting the quality of life of an individual usually as they enter older stages of life, the disc degeneration reduces the shock absorption available which in turn causes pain. Disc loss is one of the central processes in the pathogenesis of DDD. In this study, we investigated whether the image texture features quantified from magnetic resonance imaging (MRI) could be appropriate markers for diagnosis of DDD and prognosis of inter-vertebral disc loss. The main objective is to use simple image based biomarkers to perform prognosis of spinal diseases using non-invasive procedures. Our results from 65 subjects proved the higher success rates of the combination marker compared to the individual markers and in the future, we will extend the study to other spine regions to allow prognosis and diagnosis of DDD for a wider region.

  6. Acupuncture treatment for feline multifocal intervertebral disc disease.

    PubMed

    Choi, Keum Hwa; Hill, Sara A

    2009-08-01

    A 14-year-old male neutered domestic shorthair cat was admitted to the Veterinary Medical Center, University of Minnesota for evaluation of severe hind limb ataxia, atrophy and paresis. Diagnosis based on physical examination, neurological assessment and magnetic resonance imaging (MRI) was multifocal intervertebral disc disease (IVDD) with dorsal disc protrusion throughout the thoracic and cranial lumbar spine. The Oriental Medicine (OM) diagnosis (pattern identification) was painful obstruction (Bi) syndrome caused by phlegm-heat accumulation with blood stagnation in the spine. High dose prednisolone therapy (1.25mg/kg PO, once daily) initially did not show any significant improvement in clinical signs. The cat was then treated with several modes of acupuncture treatment including dry needle acupuncture, electro-acupuncture and scalp acupuncture along with Tui-Na (hand manipulation in OM) and physical therapy. Significant improvements in mobility, proprioception and spinal posture were noticed and the cat was able to rise, walk and run 4 months after starting acupuncture treatments. This is the first case report of feline IVDD with multiple sites of disc compression which was successfully treated with several modes of acupuncture treatment.

  7. Differential expression of proteoglycan epitopes by ovine intervertebral disc cells

    PubMed Central

    MELROSE, JAMES; SMITH, SUSAN; GHOSH, PETER

    2000-01-01

    The alginate bead culture system has been utilised by several groups to examine the in vitro proteoglycan (PG) metabolism of chondrocytes and intervertebral disc cells, but the nature of the PGs produced has not been examined in detail. This is largely due to the difficulty of separating the anionically charged sodium alginate support matrix from PGs which are similarly charged. In the present study ovine annulus fibrosus, transitional zone and nucleus pulposus cells were dissociated enzymatically from their respective matrices by sequential digestion with pronase/clostridial collagenase and DNAase and then cultured in alginate beads for 10 d. The beads were solubilised and subjected to DEAE Sepharose CL6B anion exchange chromatography to separate the sodium alginate bead support matrix material quantitatively from the disc cell PGs. The alginate free bead PGs were then subjected to composite agarose polyacrylamide gel electrophoresis to resolve PG populations and the PGs were transferred to nitrocellulose membranes by semidry electroblotting. The PGs were identified by probing the blots with a panel of antibodies to defined PG core protein and glycosaminoglycan side chain epitopes. Alginate beads of disc cells were also embedded in paraffin wax and 4μm sections cut to immunolocalise decorin, biglycan, versican, and the 7-D-4 PG epitope within the beads. Decorin and biglycan had similar distributions in the beads, being localised on the cell surface whereas versican and the 7-D-4 PG epitope were immunolocalised interterritoriarly. This study is the first to demonstrate that ovine disc cells synthesise versican in alginate bead culture. Furthermore the immunoblotting studies also showed that a proportion of the 7-D-4 PG epitope was colocalised with versican. PMID:11005711

  8. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats

    PubMed Central

    Issy, A.C.; Castania, V.; Castania, M.; Salmon, C.E.G.; Nogueira-Barbosa, M.H.; Bel, E. Del; Defino, H.L.A.

    2013-01-01

    Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration. PMID:23532265

  9. Reoperations Following Cervical Disc Replacement

    PubMed Central

    Skovrlj, Branko; Lee, Dong-Ho; Caridi, John Michael

    2015-01-01

    Cervical disc replacement (CDR) has emerged as an alternative surgical option to cervical arthrodesis. With increasing numbers of patients and longer follow-ups, complications related to the device and/or aging spine are growing, leaving us with a new challenge in the management and surgical revision of CDR. The purpose of this study is to review the current literature regarding reoperations following CDR and to discuss about the approaches and solutions for the current and future potential complications associated with CDR. The published rates of reoperation (mean, 1.0%; range, 0%-3.1%), revision (mean, 0.2%; range, 0%-0.5%), and removal (mean, 1.2%; range, 0%-1.9%) following CDR are low and comparable to the published rates of reoperation (mean, 1.7%; range; 0%-3.4%), revision (mean, 1.5%; range, 0%-4.7%), and removal (mean, 2.0%; range, 0%-3.4%) following cervical arthrodesis. The surgical interventions following CDR range from the repositioning to explantation followed by fusion or the reimplantation to posterior foraminotomy or fusion. Strict patient selection, careful preoperative radiographic review and surgical planning, as well as surgical technique may reduce adverse events and the need for future intervention. Minimal literature and no guidelines exist for the approaches and techniques in revision and for the removal of implants following CDR. Adherence to strict indications and precise surgical technique may reduce the number of reoperations, revisions, and removals following CDR. Long-term follow-up studies are needed, assessing the implant survivorship and its effect on the revision and removal rates. PMID:26097667

  10. Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis

    PubMed Central

    Bian, Qin; Ma, Lei; Jain, Amit; Crane, Janet L; Kebaish, Khaled; Wan, Mei; Zhang, Zhengdong; Edward Guo, X; Sponseller, Paul D; Séguin, Cheryle A; Riley, Lee H; Wang, Yongjun; Cao, Xu

    2017-01-01

    Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal (NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta (TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease (DDD). Knockout of TGFβ type II receptor (TβRII) or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD. PMID:28392965

  11. Prediction of glycosaminoglycan synthesis in intervertebral disc under mechanical loading.

    PubMed

    Gao, Xin; Zhu, Qiaoqiao; Gu, Weiyong

    2016-09-06

    The loss of glycosaminoglycan (GAG) content is a major biochemical change during intervertebral disc (IVD) degeneration. Abnormal mechanical loading is one of the major factors causing disc degeneration. In this study, a multiscale mathematical model was developed to quantify the effect of mechanical loading on GAG synthesis. This model was based on a recently developed cell volume dependent GAG synthesis theory that predicts the variation of GAG synthesis rate of a cell under the influence of mechanical stimuli, and the biphasic theory that describes the deformation of IVD under mechanical loading. The GAG synthesis (at the cell level) was coupled with the mechanical loading (at the tissue level) via a cell-matrix unit approach which established a relationship between the variation of cell dilatation and the local tissue dilatation. This multiscale mathematical model was used to predict the effect of static load (creep load) on GAG synthesis in bovine tail discs. The predicted results are in the range of experimental results. This model was also used to investigate the effect of static (0.2MPa) and diurnal loads (0.1/0.3MPa and 0.15/0.25MPa in 12/12 hours shift with an average of 0.2MPa over a cycle) on GAG synthesis. It was found that static load and diurnal loads have different effects on GAG synthesis in a diurnal cycle, and the diurnal load effects depend on the amplitude of the load. The model is important to understand the effect of mechanical loading at the tissue level on GAG synthesis at the cellular level, as well as to optimize the mechanical loading in growing engineered tissue.

  12. Role of Cytokines in Intervertebral Disc Degeneration: Pain and Disc-content

    PubMed Central

    Risbud, Makarand V.; Shapiro, Irving. M

    2014-01-01

    Degeneration of the intervertebral disc is the major contributor to back/neck and radicular pain. It is characterized by an elevation in levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1 α/β, IL-6 and IL-17 secreted by the disc cells themselves; these cytokines promote matrix degradation, chemokine production and changes in cell phenotype. The resulting imbalance between catabolic and anabolic responses leads to degeneration, as well as herniation and radicular pain. Release of chemokines from degenerating discs promote infiltration and activation of T and B cells, macrophages, neutrophils, and mast cells further amplifying the inflammatory cascade. Immunocyte migration into the disc is accompanied by the appearance of microvasculature and nerve fibers arising from the dorsal root ganglion (DRG). In this inflammatory milieu, neurogenic factors in particular nerve growth factor (NGF) and brain-derive neurotrophic factor (BDNF) generated by disc and immune cells induce expression of pain associated cation channels in DRGs. Depolarization of these channels is likely to promote discogenic and radicular pain and reinforce the cytokine-mediated degenerative cascade. Taken together, the enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provide new targets for treating symptomatic disc disease. PMID:24166242

  13. Cervical disc arthroplasty: Pros and cons

    PubMed Central

    Moatz, Bradley; Tortolani, P. Justin

    2012-01-01

    Background: Cervical disc arthroplasty has emerged as a promising potential alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. Despite a history of excellent outcomes after ACDF, the question as to whether a fusion leads to adjacent segment degeneration remains unanswered. Numerous US investigational device exemption trials comparing cervical arthroplasty to fusion have been conducted to answer this question. Methods: This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Results: Early clinical outcomes show that cervical arthroplasty is as effective as the standard ACDF. However, this new technology is also associated with an expanding list of novel complications. Conclusion: Although there is no definitive evidence that cervical disc replacement reduces the incidence of adjacent segment degeneration, it does show other advantages; for example, faster return to work, and reduced need for postoperative bracing. PMID:22905327

  14. Minimally invasive photopolymerization in intervertebral disc tissue cavities

    NASA Astrophysics Data System (ADS)

    Schmocker, Andreas M.; Khoushabi, Azadeh; Gantenbein-Ritter, Benjamin; Chan, Samantha; Bonél, Harald Marcel; Bourban, Pierre-Etienne; Mânson, Jan Anders; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

    2014-03-01

    Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerizationvolume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.

  15. Stem cell therapy for intervertebral disc regeneration: obstacles and solutions.

    PubMed

    Sakai, Daisuke; Andersson, Gunnar B J

    2015-04-01

    Intervertebral disc (IVD) degeneration is frequently associated with low back and neck pain, which accounts for disability worldwide. Despite the known outcomes of the IVD degeneration cascade, the treatment of IVD degeneration is limited in that available conservative and surgical treatments do not reverse the pathology or restore the IVD tissue. Regenerative medicine for IVD degeneration, by injection of IVD cells, chondrocytes or stem cells, has been extensively studied in the past decade in various animal models of induced IVD degeneration, and has progressed to clinical trials in the treatment of various spinal conditions. Despite preliminary results showing positive effects of cell-injection strategies for IVD regeneration, detailed basic research on IVD cells and their niche indicates that transplanted cells are unable to survive and adapt in the avascular niche of the IVD. For this therapeutic strategy to succeed, the indications for its use and the patients who would benefit need to be better defined. To surmount these obstacles, the solution will be identified only by focused research, both in the laboratory and in the clinic.

  16. Mesenchymal stem cell tracking in the intervertebral disc

    PubMed Central

    Handley, Charles; Goldschlager, Tony; Oehme, David; Ghosh, Peter; Jenkin, Graham

    2015-01-01

    Low back pain is a common clinical problem, which leads to significant social, economic and public health costs. Intervertebral disc (IVD) degeneration is accepted as a common cause of low back pain. Initially, this is characterized by a loss of proteoglycans from the nucleus pulposus resulting in loss of tissue hydration and hydrostatic pressure. Conservative management, including analgesia and physiotherapy often fails and surgical treatment, such as spinal fusion, is required. Stem cells offer an exciting possible regenerative approach to IVD disease. Preclinical research has demonstrated promising biochemical, histological and radiological results in restoring degenerate IVDs. Cell tracking provides an opportunity to develop an in-depth understanding of stem cell survival, differentiation and migration, enabling optimization of stem cell treatment. Magnetic Resonance Imaging (MRI) is a non-invasive, non-ionizing imaging modality with high spatial resolution, ideally suited for stem cell tracking. Furthermore, novel MRI sequences have the potential to quantitatively assess IVD disease, providing an improved method to review response to biological treatment. Superparamagnetic iron oxide nanoparticles have been extensively researched for the purpose of cell tracking. These particles are biocompatible, non-toxic and act as excellent MRI contrast agents. This review will explore recent advances and issues in stem cell tracking and molecular imaging in relation to the IVD. PMID:25621106

  17. Standards of Practice: Quality Assurance Guidelines for Percutaneous Treatments of Intervertebral Discs

    SciTech Connect

    Kelekis, Alexis D. Filippiadis, Dimitris K.; Martin, Jean-Baptiste; Brountzos, Elias

    2010-10-15

    Percutaneous treatments are used in the therapy of small- to medium-sized hernias of intervertebral discs to reduce the intradiscal pressure in the nucleus and theoretically create space for the herniated fragment to implode inward, thus reducing pain and improving mobility and quality of life. These techniques involve the percutaneous removal of the nucleus pulposus by using a variety of chemical, thermal, or mechanical techniques and consist of removal of all or part of nucleus pulposus to induce more rapid healing of the abnormal lumbar disc. These guidelines are written to be used in quality improvement programs for assessing fluoroscopy- and/or computed tomography-guided percutaneous intervertebral disc ablative techniques.

  18. Determination of the intervertebral disc space from CT images of the lumbar spine

    NASA Astrophysics Data System (ADS)

    Korez, Robert; Å tern, Darko; Likar, Boštjan; Pernuš, Franjo; Vrtovec, Tomaž

    2014-03-01

    Degenerative changes of the intervertebral disc are among the most common causes of low back pain, where for individuals with significant symptoms surgery may be needed. One of the interventions is the total disc replacement surgery, where the degenerated disc is replaced by an artificial implant. For designing implants with good bone contact and continuous force distribution, the morphology of the intervertebral disc space and vertebral body endplates is of considerable importance. In this study we propose a method for the determination of the intervertebral disc space from three-dimensional (3D) computed tomography (CT) images of the lumbar spine. The first step of the proposed method is the construction of a model of vertebral bodies in the lumbar spine. For this purpose, a chain of five elliptical cylinders is initialized in the 3D image and then deformed to resemble vertebral bodies by introducing 25 shape parameters. The parameters are obtained by aligning the chain to the vertebral bodies in the CT image according to image intensity and appearance information. The determination of the intervertebral disc space is finally achieved by finding the planes that fit the endplates of the obtained parametric 3D models, and placing points in the space between the planes of adjacent vertebrae that enable surface reconstruction of the intervertebral disc space. The morphometric analysis of images from 20 subjects yielded 11:3 +/- 2:6, 12:1 +/- 2:4, 12:8 +/- 2:0 and 12:9 +/- 2:7 cm3 in terms of L1-L2, L2-L3, L3-L4 and L4-L5 intervertebral disc space volume, respectively.

  19. Association between apparent diffusion coefficient and intervertebral disc degeneration in patients with ankylosing spondylitis

    PubMed Central

    Resorlu, Mustafa; Gokmen, Ferhat; Resorlu, Hatice; Adam, Gurhan; Akbal, Ayla; Cevizci, Sibel; Sariyildirim, Abdullah; Savas, Yilmaz; Guven, Mustafa; Aras, Adem Bozkurt

    2015-01-01

    Purpose: To assess the relation between ankylosing spondylitis (AS) and degenerative disc disease emerging in association with various intrinsic and extrinsic factors and to evaluate the correlation between degree of degeneration in intervertebral discs and apparent diffusion coefficient (ADC) values. Methods: Thirty-five patients with AS and a control group of 35 patients were included in the study. Three hundred fifty intervertebral discs were assessed in terms of degeneration by analyzing signal intensities and morphologies on T2 weighted series of a 1.5 Tesla magnetic resonance scanner. ADC values were determined in diffusion weighted images (DWI) using a “b value of 500 s/mm2”. Patients in the AS and control groups were compared in terms of intervertebral disc degeneration, and association between degree of degeneration and ADC values was analyzed. Results: The mean of total degeneration degrees for five lumbar intervertebral discs was significantly higher in the patients with AS compared to the control group (16.77±4.67 vs 13.00±4.08, respectively; P=0.001). When intervertebral discs were analyzed separately, disc degeneration was again significantly higher in patients with AS compared to the control group, with the exception of L5-S1. Age, cholesterol level, triglyceride level, duration of disease and BASFI index were significantly associated with degree of degeneration in patients with AS. A negative correlation was determined between disc degeneration and ADC value. Conclusion: AS is a risk factor for degenerative disc disease due to its systemic effects, the fact it leads to posture impairment and its inflammatory effects on the vertebrae. A decrease in ADC values is observed as degeneration worsens in degenerative disc disease. PMID:25785119

  20. A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

    PubMed Central

    Ghosh, Peter

    2016-01-01

    Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored. PMID:27314030

  1. Intervertebral disc regeneration: from the degenerative cascade to molecular therapy and tissue engineering.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Di Martino, Alberto; Denaro, Vincenzo

    2015-06-01

    Low back pain is one of the major health problems in industrialized countries, as a leading source of disability in the working population. Intervertebral disc degeneration has been identified as its main cause, being a progressive process mainly characterized by alteration of extracellular matrix composition and water content. Many factors are involved in the degenerative cascade, such as anabolism/catabolism imbalance, reduction of nutrition supply and progressive cell loss. Currently available treatments are symptomatic, and surgical procedures consisting of disc removal are often necessary. Recent advances in our understanding of intervertebral disc biology led to an increased interest in the development of novel biological treatments aimed at disc regeneration. Growth factors, gene therapy, stem cell transplantation and biomaterials-based tissue engineering might support intervertebral disc regeneration by overcoming the limitation of the self-renewal mechanism. The aim of this paper is to overview the literature discussing the current status of our knowledge from the degenerative cascade of the intervertebral disc to the latest molecular, cell-based therapies and tissue-engineering strategies for disc regeneration.

  2. Exploring interactions between force, repetition and posture on intervertebral disc height loss and bulging in isolated porcine cervical functional spinal units from sub-acute-failure magnitudes of cyclic compressive loading.

    PubMed

    Gooyers, Chad E; Callaghan, Jack P

    2015-10-15

    Most in vitro studies are limited in the ability to partition intervertebral disc (IVD) height loss from total specimen height loss since the net changes in the actuator position of the materials testing system simply reflect net changes to functional spinal units (FSUs) used for testing. Three levels of peak compressive force, three cycle rates and two dynamic postural conditions were examined using a full-factorial design. Cyclic compressive force was applied using a time-varying waveform with synchronous flexion/extension for 5000 cycles. Surface scans from the anterior aspect of the IVD were recorded in a neutral and flexed posture before and after the cyclic loading protocol using a 3D laser scanner to characterise changes in IVD height loss and bulging. A significant three-way interaction (p=0.0092) between the magnitude of peak compressive force, cycle rate and degree of postural deviation was observed in cycle-varying specimen height loss data. A significant main effect of peak compressive force (p=0.0003) was also observed in IVD height loss calculated from the surface profiles of the IVD. The relative contribution of IVD height loss (measured on the anterior surface) to total specimen height loss across experimental conditions varied considerably, ranging from 19% to 58%. Postural deviation was the only factor that significantly affected the magnitude of peak AF bulge (p=0.0016). This investigation provides evidence that total specimen height loss is not an accurate depiction of cycle-varying changes in the IVD across a range of in vivo scenarios that were replicated with in vitro testing.

  3. Changes in intervertebral disc cross-sectional area with bed rest and space flight

    NASA Technical Reports Server (NTRS)

    LeBlanc, A. D.; Evans, H. J.; Schneider, V. S.; Wendt, R. E. 3rd; Hedrick, T. D.

    1994-01-01

    STUDY DESIGN. We measured the cross-sectional area of the intervertebral discs of normal volunteers after an overnight rest; before, during, and after 5 or 17 weeks of bed rest; and before and after 8 days of weightlessness. OBJECTIVES. This study sought to determine the degree of expansion of the lumbar discs resulting from bed rest and space flight. SUMMARY OF BACKGROUND DATA. Weightlessness and bed rest, an analog for weightlessness, reduce the mechanical loading on the musculoskeletal system. When unloaded, intervertebral discs will expand, increasing the nutritional diffusion distance and altering the mechanical properties of the spine. METHODS. Magnetic resonance imaging was used to measure the cross-sectional area and transverse relaxation time (T2) of the intervertebral discs. RESULTS. Overnight or longer bed rest causes expansion of the disc area, which reaches an equilibrium value of about 22% (range 10-40%) above baseline within 4 days. Increases in disc area were associated with modest increases in disc T2. During bed rest, disc height increased approximately 1 mm, about one-half of previous estimates based on body height measurements. After 5 weeks of bed rest, disc area returned to baseline within a few days of ambulation, whereas after 17 weeks, disc area remained above baseline 6 weeks after reambulation. After 8 days of weightlessness, T2, disc area, and lumbar length were not significantly different from baseline values 24 hours after landing. CONCLUSIONS. Significant adaptive changes in the intervertebral discs can be expected during weightlessness. These changes, which are rapidly reversible after short-duration flights, may be an important factor during and after long-duration missions.

  4. Fusion versus Bryan Cervical Disc in two-level cervical disc disease: a prospective, randomised study

    PubMed Central

    Nie, Lin; Zhang, Li; Hou, Yong

    2008-01-01

    In this prospective study, our aim was to compare the functional results and radiographic outcomes of fusion and Bryan Cervical Disc replacement in the treatment of two-level cervical disc disease. A total of 65 patients with two-level cervical disc disease were randomly assigned to two groups, those operated on with Bryan Cervical Disc replacement (31) and those operated on with anterior cervical fusion with an iliac crest autograft and plate (34). Clinical evaluation was carried out using the visual analogue scale (VAS), the Short Form 36 (SF-36) and the neck disability index (NDI) during a two year follow-up. Radiological evaluation sought evidence of range of motion, stability and subsidence of the prosthesis. Substantial reduction in NDI scores occurred in both groups, with greater percent improvement in the Bryan group (P = 0.023). The arm pain VAS score improvement was substantial in both groups. Bryan artificial cervical disc replacement seems reliable and safe in the treatment of patients with two-level cervical disc disease. PMID:18956190

  5. Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration

    PubMed Central

    Silveira, João W.; Issy, Ana Carolina; Castania, Vitor A.; Salmon, Carlos E. G.; Nogueira-Barbosa, Marcello H.; Guimarães, Francisco S.; Defino, Helton L. A.; Bel, Elaine Del

    2014-01-01

    Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol) injected immediately after lesion were analyzed acutely (2 days) by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration. PMID:25517414

  6. Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration.

    PubMed

    Silveira, João W; Issy, Ana Carolina; Castania, Vitor A; Salmon, Carlos E G; Nogueira-Barbosa, Marcello H; Guimarães, Francisco S; Defino, Helton L A; Del Bel, Elaine

    2014-01-01

    Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol) injected immediately after lesion were analyzed acutely (2 days) by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.

  7. Effect of repetitive laser pulses on the electrical conductivity of intervertebral disc tissue

    SciTech Connect

    Omel'chenko, A I; Sobol', E N

    2009-03-31

    The thermomechanical effect of 1.56-{mu}m fibre laser pulses on intervertebral disc cartilage has been studied using ac conductivity measurements with coaxial electrodes integrated with an optical fibre for laser radiation delivery to the tissue. The observed time dependences of tissue conductivity can be interpreted in terms of hydraulic effects and thermomechanical changes in tissue structure. The laserinduced changes in the electrical parameters of the tissue are shown to correlate with the structural changes, which were visualised using shadowgraph imaging. Local ac conductivity measurements in the bulk of tissue can be used to develop a diagnostic/monitoring system for laser regeneration of intervertebral discs. (laser biology and medicine)

  8. Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs.

    PubMed

    Li, Fang-Cai; Zhang, Ning; Chen, Wei-Shan; Chen, Qi-Xin

    2010-08-01

    The intravertebral vacuum phenomenon (VP) is usually associated with degenerative disc disease, which could be related to the low back pain. Various theories related to the pathogenesis of VP have been proposed, but these theories have not been critically examined and remain hypothetical. In this article, we review the possible role of endplate degeneration in the pathogenesis of VP, and discuss several pathways possibly linked to them. Due to the endplate calcification and activated cytokines, the transport pathway of the nutrition for the intervertebral disc was blocked, resulting in the metabolic unbalance and decrease of the synthesis of matrix structural proteins. It could promote the matrix decomposition, causing the decrease of the quantity of matrix and the changes of stress distribution in intervertebral disc. As a result, the structure of intervertebral discs became increasingly unstable. While compression happened, the intravertebral cleft could occur and be gradually filled with gas, which may cause low back pain and aggravate the intervertebral discs degeneration. As outlined above, we hypothesize that endplate degeneration might be the origination of the vacuum phenomenon.

  9. Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs

    PubMed Central

    Schaaf, Rainer; Wälchli, Beat; Boos, Norbert

    2006-01-01

    While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0–86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26–69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly “deeper” blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly “deeper” extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc

  10. Material Science in Cervical Total Disc Replacement

    PubMed Central

    Pham, Martin H.; Mehta, Vivek A.; Tuchman, Alexander; Hsieh, Patrick C.

    2015-01-01

    Current cervical total disc replacement (TDR) designs incorporate a variety of different biomaterials including polyethylene, stainless steel, titanium (Ti), and cobalt-chrome (CoCr). These materials are most important in their utilization as bearing surfaces which allow for articular motion at the disc space. Long-term biological effects of implanted materials include wear debris, host inflammatory immune reactions, and osteolysis resulting in implant failure. We review here the most common materials used in cervical TDR prosthetic devices, examine their bearing surfaces, describe the construction of the seven current cervical TDR devices that are approved for use in the United States, and discuss known adverse biological effects associated with long-term implantation of these materials. It is important to appreciate and understand the variety of biomaterials available in the design and construction of these prosthetics and the considerations which guide their implementation. PMID:26523281

  11. Low-level vibrations maintain the intervertebral disc during unloading

    NASA Astrophysics Data System (ADS)

    Holguin, Nilsson

    Changes in intervertebral disc (IVD) biochemistry, morphology and mechanics have been characterized only incompletely in the rat hindlimb unloading (HU) model. Although exposure to chronic vibrations can be damaging, low-magnitude vibrations can attenuate the geometric changes of the IVD due to altered spinal loading. Here, we tested the hypothesis that low-magnitude, high-frequency vibrations will mitigate the hypotrophy, biochemical degradation and deconditioning of the IVD during HU. When applied as whole-body vibrations through all four paws, Sprague-Dawley rats were subjected to HU and exposed to daily periods (15min/d) of either ambulatory activities (HU+AMB) or whole body vibrations superimposed upon ambulation (HU+WBV; WBV at 45Hz, 0.3g). After 4wks and, compared to age-matched control rats (AC), the lumbar IVD of HU+AMB had a 22% smaller glycosaminoglycans/collagen ratio, 12% smaller posterior IVD height, and 13% smaller cross-sectional area. Compared to HU+AMB rats, the addition of low-level vibratory loading did not significantly alter IVD biochemistry, posterior height, area, or volume, but directionally altered IVD geometry. When subjected to upright vibrations through the hindpaws, rats were HU for 4wks. A subset of HU rats stood in an upright posture on a vertically oscillating plate (0.2g) at 45- or 90-Hz (HU+45 or HU+90). After 4wks, regardless of sham (HU+SC) loading (HU+/-SC) and, compared to AC, IVD of HU+/-SC had 10% less height, 39% smaller nucleus pulposus area, less glycosaminoglycans in the nucleus pulposus (21%), anterior annulus fibrosus (16%) and posterior annulus fibrosus (19%), 76% less tension-compression neutral zone (NZ) modulus, 26% greater compressive modulus, 25% greater initial elastic damping modulus, 26% less torsional NZ stiffness, no difference in collagen content and a weaker relationship between tension-compression NZ modulus and posterior height change. Exogenously introduced oscillations maintained the morphology

  12. Microstructure-based fiber optic pressure sensor for measurements in lumbar intervertebral discs

    NASA Astrophysics Data System (ADS)

    Hoejer, Svante; Krantz, Martin; Ekstroem, Lars; Kaigle, Allison; Holm, Sten

    1999-01-01

    A fiberoptic system with a microstructure sensor element was used for measuring lumbar intervertebral disc pressure in a porcine model. The fiberoptic pressure sensor was inserted in the disc using a guiding needle. A reference sensor was also introduced into the same area of an adjacent disc. The fiberoptic sensor detected pressures from 0.7-8 bar in the disc. Dynamic measurements were carried out at frequencies between 2 and 10 Hz. No phase lag was observed between the applied force and the measured pressures. Sensitivity, dynamic response and available pressure range are all important design characteristics for which this fiberoptic sensor has a competitive edge.

  13. [Dorsal extrusion of intervertebral disc as a cause of cauda equina syndrome].

    PubMed

    Jusić, Aldin; Skomorac, Rasim; Beculić, Hakija

    2011-01-01

    We have presented a case of rare dorsally sequestrated lumbar disc herniation manifesting as cauda equina syndrome. The patient was admitted to the Neurological Department of Canton Hospital Zenica due to urinary retention and weakness in both lower extremities. Magnetic resonance imaging showed a compressing mass located in the dorsal extradural space at the L2-L3 level. An extruded intervertebral disc was found intraoperatively. The decompression was followed by good recovery.

  14. Effects of psoralen on chondrocyte degeneration in lumbar intervertebral disc of rats.

    PubMed

    Yang, Libin; Sun, Xiaohui; Geng, Xiaolin

    2015-03-01

    Discuss the internal mechanism of delaying degeneration of lumber intervertebral disc. The cartilage of lumbar intervertebral disc of SD rats was selected in vitro, then cultured by tissue explant method, and identified by HE staining, toluidine blue staining and immunofluorescence. The optimal concentration of psoralen was screened by cell proliferation assay and RT-PCR method. The cells in third generation with good growth situation is selected and placed in 6-well plate at concentration of 1×10(5)/well and its expression was tested. Compared to concentration of 0, the mRNA expression of Col2al (Collagen Ⅱ) secreted by was up regulated chondrocyte of lumbar intervertebral disc at the concentration of 12.5 and 25μM (P<0.0 or P<0.01). The aggrecan mRNA of psoralen group was higher than blank control group (P<0.01); compared with IL-1β induced group, the mRNA expression of Col2al was significantly increased but the mRNA expression of ADAMTS-5 was significantly decreased in psoralen group (P<0.01). These findings suggest that, psoralen can remit the degeneration of lumbar intervertebral disc induced by IL-1β to some extent, and affect the related factors of IL-1β signaling pathway.

  15. Apparent diffusion coefficient in normal and abnormal pattern of intervertebral lumbar discs: initial experience☆

    PubMed Central

    Niu, Gang; Yu, Xuewen; Yang, Jian; Wang, Rong; Zhang, Shaojuan; Guo, Youmin

    2011-01-01

    The aim of the present study was to compare the relationship of morphologically defined non-bulging/herniated, bulging and herniated intervertebral lumbar discs with quantitative apparent diffusion coefficient (ADC). Thirty-two healthy volunteers and 28 patients with back pain or sciatica were examined by MRI. All intervertebral lumbar discs from L1 to S1 were classified according to morphological abnormality and degenerated grades. The ADC values of nucleus pulposus (NP) were measured and recorded. The significant differences about mean ADC values of NP were found between non-bulging/herniated discs and bulging discs as well as herniated discs (P < 0.05), whereas there were no significant differences in ADC values between bulging and herniated discs (P > 0.05). Moreover, statistically significant relationship was found in the mean ADC values of NP between “non-bulging/herniated and non-degenerated discs” and “non-bulging/herniated degenerated discs” as well as herniated discs (P < 0.05). Linear regression analysis between ADC value and disc level revealed an inverse correlation (r = -0.18). The ADC map of the NP is a potentially useful tool for the quantitative assessment of componential and molecular alterations accompanied with lumbar disc abnormalities. PMID:23554690

  16. Expression of the two pore domain potassium channel TREK-1 in human intervertebral disc cells.

    PubMed

    Sharma, Pankaj; Hughes, Stephen; El Haj, Alicia; Maffulli, Nicola

    2012-07-01

    Potassium channels play a major role in intracellular homeostasis and regulation of cell volume. Intervertebral disc cells respond to mechanical loading in a complex manner. Mechanical loading may play a role in disc degeneration. Lumbar intervertebral disc samples from 5 patients (average age: 47 years, range: 25-64 years) were used for this study, investigating cells from the nucleus pulposus and the annulus fibrosus duplicate samples to determine RNA expression and protein expression. Analysis of mRNA expression by RT-PCR demonstrated that TREK 1 was expressed by nucleus pulposus (n=5) and annulus fibrosus (n=5) cells. Currently, TREK-1 is the only potassium channel known to be activated by intracellular acidosis, and responds to mechanical and chemical stimuli. Whilst the precise role of potassium channels in cellular homeostasis remains to be determined, TREK-1 may be important to protect disc cells against ischaemic damage, and subsequent disc degeneration, and may also play a role in effecting mechanotransduction. Further research is required to fully elucidate the role of the TREK-1 ion channel in intervertebral disc cells.

  17. Metabolic Syndrome Components Are Associated with Intervertebral Disc Degeneration: The Wakayama Spine Study

    PubMed Central

    Teraguchi, Masatoshi; Yoshimura, Noriko; Hashizume, Hiroshi; Muraki, Shigeyuki; Yamada, Hiroshi; Oka, Hiroyuki; Minamide, Akihito; Ishimoto, Yuyu; Nagata, Keiji; Kagotani, Ryohei; Tanaka, Sakae; Kawaguchi, Hiroshi; Nakamura, Kozo; Akune, Toru; Yoshida, Munehito

    2016-01-01

    Objective The objective of the present study was to examine the associations between metabolic syndrome (MS) components, such as overweight (OW), hypertension (HT), dyslipidemia (DL), and impaired glucose tolerance (IGT), and intervertebral disc degeneration (DD). Design The present study included 928 participants (308 men, 620 women) of the 1,011 participants in the Wakayama Spine Study. DD on magnetic resonance imaging was classified according to the Pfirrmann system. OW, HT, DL, and IGT were assessed using the criteria of the Examination Committee of Criteria for MS in Japan. Results Multivariable logistic regression analysis revealed that OW was significantly associated with cervical, thoracic, and lumbar DD (cervical: odds ratio [OR], 1.28; 95% confidence interval [CI], 0.92–1.78; thoracic: OR, 1.75; 95% CI, 1.24–2.51; lumbar: OR, 1.87; 95% CI, 1.06–3.48). HT and IGT were significantly associated with thoracic DD (HT: OR, 1.54; 95% CI, 1.09–2.18; IGT: OR, 1.65; 95% CI, 1.12–2.48). Furthermore, subjects with 1 or more MS components had a higher OR for thoracic DD compared with those without MS components (vs. no component; 1 component: OR, 1.58; 95% CI, 1.03–2.42; 2 components: OR, 2.60; 95% CI, 1.62–4.20; ≥3 components: OR, 2.62; 95% CI, 1.42–5.00). Conclusion MS components were significantly associated with thoracic DD. Furthermore, accumulation of MS components significantly increased the OR for thoracic DD. These findings support the need for further studies of the effects of metabolic abnormality on DD. PMID:26840834

  18. Water diffusion pathway, swelling pressure, and biomechanical properties of the intervertebral disc during compression load

    SciTech Connect

    Ohshima, H.; Tsuji, H.; Hirano, N.; Ishihara, H.; Katoh, Y.; Yamada, H. )

    1989-11-01

    The behavior of water in the intervertebral disc of pig tail and its physiologic and biomechanical properties were investigated in relation to compression load. The water content, chemical composition, and swelling pressure in the intervertebral disc were measured, and the mechanism of the generation of the swelling pressure in relation to compression load stress was studied. The swelling pressure, through regulation of the water content of the disc and the resistance of the external load, differs with the region of the intervertebral disc. In the nucleus pulposus and the inner layer of the anulus fibrosus, the swelling pressure rises in proportion to the load, but few changes occur in the outer layer of the anulus fibrosus, and the constant pressure environment is thus maintained. The tritiated water (3H2O) uptake of the disc under various loads was measured. The molar partition coefficient of tritiated water is almost equal to 1 even under a compression load, which suggests that water is freely exchangeable. The diffusion of 3H2O in the intervertebral disc was traced using two pathway models: the perianular route and the end-plate route. The diffusion of water in the unloaded disc for both uptake and washout was about 2 to 3 times larger in the perianular route than in the end-plate route. Under load, the water diffusion was inhibited in both pathways. The relation between the load and displacement revealed viscoelastic properties indicating creep and stress relaxation. Young's modulus and the stiffness increased with a rise in load speed.

  19. Atomic Absorption Spectrometry Analysis of Trace Elements in Degenerated Intervertebral Disc Tissue

    PubMed Central

    Kubaszewski, Łukasz; Zioła-Frankowska, Anetta; Frankowski, Marcin; Nowakowski, Andrzej; Czabak-Garbacz, Róża; Kaczmarczyk, Jacek; Gasik, Robert

    2014-01-01

    Background Few studies have investigated trace elements (TE) in human intervertebral disc (IVD) tissue. Trace element presence can have diverse meanings: essential TE show the metabolic modalities of the tissue, while environmentally-related TE indicate pollution and tissue-specific absorption and accumulation. IVD is a highly specific compartment with impaired communication with adjacent bone. Analysis of TE in IVD provides new insights regarding tissue metabolism and IVD communication with other tissues. Material/Methods Thirty intervertebral discs were acquired from 22 patients during surgical treatment for degenerative disease. Atomic absorption spectrometry was used to evaluate the concentrations of Al, Cd, Pb, Cu, Ni, Mo, Mg, and Zn. Results Al, Pb, Cu, Mg, and Zn were detected in all samples. Pb was significantly positively correlated with age, and Ni concentration was weakly correlated with population count in the patient’s place of residence. Only Cu was observed in higher concentrations in IVD compared to in other tissues. Significant positive correlations were observed between the following pairs: Mg/Zn, Mg/Al, Mg/Pb, Zn/Al, Zn/Pb, and Al/Pb. Negative correlations were observed between Mg/Cd, Zn/Cd, Mg/Mo, and Mo/Pb. Conclusions This study is one of few to profile the elements in intervertebral discs in patients with degenerative changes. We report significant differences between trace element concentrations in intervertebral discs compared to in other tissues. Knowledge of the TE accumulation pattern is vital for better understanding intervertebral disc nutrition and metabolism. PMID:25366266

  20. Intervertebral disc degeneration: evidence for two distinct phenotypes

    PubMed Central

    Adams, Michael A; Dolan, Patricia

    2012-01-01

    We review the evidence that there are two types of disc degeneration. ‘Endplate-driven’ disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. ‘Annulus-driven’ disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct. PMID:22881295

  1. Increased Risk for Adhesive Capsulitis of the Shoulder following Cervical Disc Surgery

    PubMed Central

    Kang, Jiunn-Horng; Lin, Herng-Ching; Tsai, Ming-Chieh; Chung, Shiu-Dong

    2016-01-01

    Shoulder problems are common in patients with a cervical herniated intervertebral disc (HIVD). This study aimed to explore the incidence and risk of shoulder capsulitis/tendonitis following cervical HIVD surgery. We used data from the Taiwan “Longitudinal Health Insurance Database”. We identified all patients who were hospitalized with a diagnosis of displacement of a cervical HIVD and who underwent cervical surgery (n = 1625). We selected 8125 patients who received cervical HIVD conservative therapy only as the comparison group matched with study patients. We individually tracked these sampled patients for 6 months to identify all patients who received a diagnosis of shoulder tendonitis/capsulitis. We found that incidence rates of shoulder tendonitis/capsulitis during the 6-month follow-up period were 3.69 (95% CI: 2.49~5.27) per 100 person-years for the study group and 2.33 (95% CI: 1.89~2.86) per 100 person-years for the comparison group. Cox proportional hazard regressions showed that the adjusted hazard ratio for shoulder tendonitis/capsulitis among patients who underwent cervical disc surgery was 1.66 (95% CI = 1.09~2.53) when compared to comparison group. We concluded that patients who underwent surgery for a cervical HIVD had a significantly higher risk of developing shoulder capsulitis/tendonitis in 6 months follow-up compared to patients who received cervical HIVD conservative therapy only. PMID:27231090

  2. Effectiveness of cervical hemilaminectomy in canine Hansen Type I and Type II disc disease: a retrospective study.

    PubMed

    Schmied, Oliver; Golini, Lorenzo; Steffen, Frank

    2011-01-01

    Medical records of 41 dogs, including 15 small breed dogs (<15 kg) and 26 large breed dogs (>15 kg), with cervical intervertebral disc disease (IVDD) that underwent a hemilaminectomy were reviewed. Dogs were diagnosed using myelography, computed tomography/myelography, or MRI, and dogs were classified as having either Hansen Type I disc extrusion or Hansen Type II disc protrusion located ventrally, ventrolaterally, or laterally within the cervical spinal canal. The most common clinical presentation was ambulatory tetraparesis and/or lameness (44%). The most affected sites for cervical IVDD were between the sixth and seventh cervical vertebrae (C6-C7; 78% of Hansen Type II discs) and C2-C3 (86% of Hansen Type I discs). Treatment was effective in 88% of dogs. Five large breed dogs (12%) did not improve. In dogs with a Hansen Type I disc extrusion, clinical signs improved in 96% of the cases. In dogs with a Hansen Type II disc protrusion, an excellent and good outcome was seen in 47% and 32% of cases, respectively. Outcome was significantly better for small breed dogs and dogs with Hansen Type I disc disease compared with large breed dogs and dogs with Hansen Type II disc disease.

  3. Intervertebral disc magnetic resonance image: correlation with gross morphology and biochemical composition

    PubMed Central

    Bishop, Paul B

    1993-01-01

    The magnetic resonance image, gross morphology, and biochemical composition of the intervertebral disc nucleus pulposus (NP), anulus fibrosus (AF) and cartilaginous endplates (CEP) from two groups of three human lumbar spines were compared. Group I consisted of all healthy discs from young donors (Grade I) and group II was comprised of discs that had undergone degeneration and age-related changes (average Grade 4). The gross morphological changes in the individual disc tissues associated with ageing/degeneration were consistent with specific changes in the characteristics of the magnetic resonance image. In particular, the mid-nuclear band of decreased magnetic resonance signal intensity seen in Grade 4 discs was associated with the appearance of clefts and fissures as well as a region of mucinous infiltration. The results of the biochemical analysis suggest that the changes in signal intensity are not due merely to changes in water content, but are also associated with changes in proteoglycan content. The changes associated with ageing/degeneration in the magnetic resonance image of the disc were related to a decrease in the proteoglycan content of the AF and NP. The water content of the NP also decreased. There was no clear association between the biochemical composition of the CEP and the magnetic resonance image. These results demonstrate that magnetic resonance imaging is an effective technique for evaluating subtle morphological changes in the intervertebral disc tissues and may be a sensitive indicator of the proteoglycan content of the AF and NP. ImagesFigure 1Figure 2

  4. Current insights and controversies in the pathogenesis and diagnosis of disc-associated cervical spondylomyelopathy in dogs.

    PubMed

    De Decker, S; da Costa, R C; Volk, H A; Van Ham, L M L

    2012-11-24

    Disc-associated cervical spondylomyelopathy (DA-CSM) is the most common cause of cervical spondylomyelopathy in dogs. In this condition, progressive caudal cervical spinal cord compression is typically caused by protrusion of one or more intervertebral discs. This disc-associated compression is sometimes seen in combination with mild vertebral abnormalities and dorsal compression resulting from ligamentum flavum hypertrophy. The intervertebral disc space between the sixth (C6) and seventh (C7) cervical vertebrae is most commonly affected. Although several large breed dogs can be affected, the adult to older dobermann is overrepresented. Clinical signs vary from cervical hyperaesthesia to tetraplegia. Dogs can present with a chronic progressive or an acute onset of clinical signs. Many aspects of this multifactorial neurological syndrome are not completely understood and are the subject of controversy and debate. Although several factors have been proposed, the underlying pathology and aetiology remain unknown. Recently, new insights have been gained in the pathogenesis, diagnosis and treatment of this challenging neurological syndrome. This review outlines current controversies and new developments concerning the pathogenesis and diagnosis of DA-CSM.

  5. Parametric modeling of the intervertebral disc space in 3D: application to CT images of the lumbar spine.

    PubMed

    Korez, Robert; Likar, Boštjan; Pernuš, Franjo; Vrtovec, Tomaž

    2014-10-01

    Gradual degeneration of intervertebral discs of the lumbar spine is one of the most common causes of low back pain. Although conservative treatment for low back pain may provide relief to most individuals, surgical intervention may be required for individuals with significant continuing symptoms, which is usually performed by replacing the degenerated intervertebral disc with an artificial implant. For designing implants with good bone contact and continuous force distribution, the morphology of the intervertebral disc space and vertebral body endplates is of considerable importance. In this study, we propose a method for parametric modeling of the intervertebral disc space in three dimensions (3D) and show its application to computed tomography (CT) images of the lumbar spine. The initial 3D model of the intervertebral disc space is generated according to the superquadric approach and therefore represented by a truncated elliptical cone, which is initialized by parameters obtained from 3D models of adjacent vertebral bodies. In an optimization procedure, the 3D model of the intervertebral disc space is incrementally deformed by adding parameters that provide a more detailed morphometric description of the observed shape, and aligned to the observed intervertebral disc space in the 3D image. By applying the proposed method to CT images of 20 lumbar spines, the shape and pose of each of the 100 intervertebral disc spaces were represented by a 3D parametric model. The resulting mean (±standard deviation) accuracy of modeling was 1.06±0.98mm in terms of radial Euclidean distance against manually defined ground truth points, with the corresponding success rate of 93% (i.e. 93 out of 100 intervertebral disc spaces were modeled successfully). As the resulting 3D models provide a description of the shape of intervertebral disc spaces in a complete parametric form, morphometric analysis was straightforwardly enabled and allowed the computation of the corresponding

  6. Distinct Intervertebral Disc Cell Populations Adopt Similar Phenotypes in Three-Dimensional Culture

    PubMed Central

    Chou, Alice I.; Reza, Anna T.

    2008-01-01

    Tissue engineering strategies have the potential to improve upon current techniques for intervertebral disc repair. However, determining a suitable biomaterial scaffold for disc regeneration is difficult due to the complex fibrocartilaginous structure of the tissue. In this study, cells isolated from three distinct regions of the intervertebral disc, the outer and inner annulus fibrosus and nucleus pulposus, were expanded and seeded on resorbable polyester fiber meshes and encapsulated in calcium crosslinked alginate hydrogels, both chosen to approximate the native tissue architecture. Three-dimensional (3D) constructs were cultured for 14 days in vitro and evaluated histologically and quantitatively for gene expression and production of types I and II collagen and proteoglycans. During monolayer expansion, the cell populations maintained their distinct phenotypic morphology and gene expression profiles. However, after 14 days in 3D culture, there were no significant differences in morphology, gene expression, or protein production between all three cell populations grown in either alginate or polyester fiber meshes. The results of this study indicate that the culture environment may have a greater impact on cellular behavior than the intrinsic origin of the cells, and suggest that only a single-cell type may be required for intervertebral disc regenerative therapies. PMID:18636941

  7. Experimental Application of Bone Marrow Mesenchymal Stem Cells for the Repair of Intervertebral Disc Annulus Fibrosus

    PubMed Central

    Li, Xiaohe; Zhang, Yunfeng; Song, Bin; En, He; Gao, Shang; Zhang, Shaojie; Cai, Yongqiang; Li, Zhi-jun; Li, Cunbao; Wang, Weiping; Wang, Xin; Wang, Haiyan; Wang, Zhiqiang; Zhang, Qi; Ma, Jierong

    2016-01-01

    Background This study provides experimental results on the applicability of bone marrow mesenchymal stem cells (BMSCs) for the repair of intervertebral disc annulus fibrosus in rabbits. Material/Method Thirty healthy rabbits were randomized into an observation group (n=15) and a control group (n=15). Both groups underwent degeneration of intervertebral disc annulus fibrosus. The observation group was treated with a solution of BMSCs and dexamethasone sodium phosphate, while the control group was treated with dexamethasone sodium phosphate only. Results The two groups were compared for efficacy and pathological conditions after treatment. Both disc height index and level of type II collagen in nucleus pulposus were significantly higher in the observation group than in the control group at 2, 4, 8, and 12 weeks after degeneration (p<0.05 for all comparisons). The percentages of grade 0 and grade 1 were significantly higher in the observation group than in the control group (p<0.05 for both grade 0 and 1 comparisons), while the percentage of grade 4 and grade 5 were significantly lower in the observation group than in the control group (p<0.05 for both grade 4 and 5 comparisons). Conclusions BMSCs cultured in vitro can effectively repair intervertebral disc annulus fibrosus, which is of positive significance, and thus is clinically recommended. PMID:27857031

  8. Cervical spine intervertebral kinematics with respect to the head are different during flexion and extension motions

    PubMed Central

    Anderst, William J.; Donaldson, William F.; Lee, Joon Y.; Kang, James D.

    2013-01-01

    Previous dynamic imaging studies of the cervical spine have focused entirely on intervertebral kinematics while neglecting to investigate the relationship between head motion and intervertebral motion. Specifically, it is unknown if the relationship between head and intervertebral kinematics is affected by movement direction. We tested the hypothesis that there would be no difference in sagittal plane intervertebral angles at identical head orientations during the flexion and extension movements. Nineteen asymptomatic subjects performed continuous head flexion-extension movements while biplane radiographs were collected at 30 images per second. A previously validated model-based volumetric tracking process determined three-dimensional vertebral position with sub-millimeter accuracy throughout the flexion–extension motion. Head movement was recorded at 60 Hz using conventional motion analysis and reflective markers. Intervertebral angles were determined at identical head orientations during the flexion and extension movements. Cervical motion segments were in a more extended orientation during flexion and in a more flexed orientation during extension for any given head orientation. The results suggest that static radiographs cannot accurately represent vertebral orientation during dynamic motion. Further, data should be collected during both flexion and extension movements when investigating intervertebral kinematics with respect to global head orientation. Also, in vitro protocols that use intervertebral total range of motion as validation criteria may be improved by assessing model fidelity using continuous intervertebral kinematics in flexion and in extension. Finally, musculoskeletal models of the head and cervical spine should account for the direction of head motion when determining muscle moment arms because vertebral orientations (and therefore muscle attachment sites) are dependent on the direction of head motion. PMID:23540377

  9. Evidence for an Important Role of Smad-7 in Intervertebral Disc Degeneration

    PubMed Central

    Li, Bo; Su, Yi-Jun; Zheng, Xin-Feng; Yang, Yue-Hua; Jiang, Sheng-Dan

    2015-01-01

    Smad-7 inhibited the transforming growth factor beta (TGF-β)-induced proteoglycan synthesis in chondrocytes and completely antagonized the effect of TGF-β on the proliferation of the cells. The aim of this study was to evaluate the contribution of Smad-7 to the pathophysiology of disc degeneration by determining the expression of Smad-7 in the degenerative intervertebral discs and its effect on the extracellular matrix metabolism of disc cells. Instability of the lumbar spine produced by imbalanced dynamic and static forces was used to induce intervertebral disc degeneration in rats. The expression of Smad-7 was assessed by the immunohistochemical method. Disc cell apoptosis was detected by in situ TUNEL staining. The effect of Smad-7 overexpression on the matrix metabolism of disc cells was analyzed in vitro by real-time polymerase chain reaction (PCR) and Western blotting. Finally, intradiscal injection of the Smad-7 overexpression lentivirus was performed to evaluate the in vivo effect of Smad-7 on disc degeneration. Radiographic and histomorphological examinations showed that lumbar disc degeneration became more and more severe in the rats with induced instability. Immunohistochemical observation demonstrated increasing protein expression of Smad-7 in the degenerative discs. A significantly positive correlation was found between Smad-7 expression and the degree of disc degeneration and between Smad-7 expression and disc cell apoptosis. Overexpression of Smad-7 in disc cells inhibited the expression of TGF-β1, collagen type-I, collagen type-II, and aggrecan and promoted the expression of MMP-13, but did not change the expression of ADAMTS-5. The in vivo findings illustrated that intradiscal injection of lentivirus vector with Smad-7 overexpression accelerated the progress of disc degeneration. In conclusion, Smad-7 was highly expressed in the degenerative discs. Overexpression of Smad-7 weakened the protective role of TGF-β and accelerated the progress of

  10. Continuous lumbar hemilaminectomy for intervertebral disc disease in an Amur tiger (Panthera tigris altaica).

    PubMed

    Flegel, Thomas; Böttcher, Peter; Alef, Michaele; Kiefer, Ingmar; Ludewig, Eberhard; Thielebein, Jens; Grevel, Vera

    2008-09-01

    A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset of paraplegia. Spinal imaging that included plain radiographs, myelography, and computed tomography performed under general anesthesia revealed lateralized spinal cord compression at the intervertebral disc space L4-5 caused by intervertebral disc extrusion. This extrusion was accompanied by an extensive epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from L3 to L6 was performed, resulting in complete decompression of the spinal cord. The tiger was ambulatory again 10 days after the surgery. This case suggests that the potential benefit of complete spinal cord decompression may outweigh the risk of causing clinically significant spinal instability after extensive decompression.

  11. Changes in intervertebral disc morphology persist 5 mo after 21-day bed rest.

    PubMed

    Belavý, Daniel L; Bansmann, P Martin; Böhme, Gisela; Frings-Meuthen, Petra; Heer, Martina; Rittweger, Jörn; Zange, Jochen; Felsenberg, Dieter

    2011-11-01

    As part of the nutrition-countermeasures (NUC) study in Cologne, Germany in 2010, seven healthy male subjects underwent 21 days of head-down tilt bed rest and returned 153 days later to undergo a second bout of 21-day bed rest. As part of this model, we aimed to examine the recovery of the lumbar intervertebral discs and muscle cross-sectional area (CSA) after bed rest using magnetic resonance imaging and conduct a pilot study on the effects of bed rest in lumbar muscle activation, as measured by signal intensity changes in T(2)-weighted images after a standardized isometric spinal extension loading task. The changes in intervertebral disc volume, anterior and posterior disc height, and intervertebral length seen after bed rest did not return to prebed-rest values 153 days later. While recovery of muscle CSA occurred after bed rest, increases (P ≤ 0.016) in multifidus, psoas, and quadratus lumborum muscle CSA were seen 153 days after bed rest. A trend was seen for greater activation of the erector spinae and multifidus muscles in the standardized loading task after bed rest. Greater reductions of multifidus and psoas CSA muscle and greater increases in multifidus signal intensity with loading were associated with incidence of low back pain in the first 28 days after bed rest (P ≤ 0.044). The current study contributes to our understanding of the recovery of the lumbar spine after 21-day bed rest, and the main finding was that a decrease in spinal extensor muscle CSA recovers within 5 mo after bed rest but that changes in the intervertebral discs persist.

  12. Intervertebral disc extrusion and spinal decompression in a binturong (Arctictis binturong).

    PubMed

    Spriggs, Maria; Arble, Jason; Myers, Gwen

    2007-03-01

    A 10-yr-old binturong (Arctictis binturong) developed an acute onset of hind limb paralysis. Neurological examination revealed sensorimotor paraplegia. Myelography and computed tomography demonstrated a ventrolateral extradural compression of the spinal cord centered over the L3-L4 intervertebral disc space. Spinal decompression was performed via hemilaminectomy and excision of degenerate nucleus pulposus, confirmed by histopathologic examination. The binturong regained slight motor function by day 8 postoperatively but succumbed to pancreatitis 19 days postoperatively.

  13. Surgical anatomy, radiological features, and molecular biology of the lumbar intervertebral discs.

    PubMed

    Ghannam, Malik; Jumah, Fareed; Mansour, Shaden; Samara, Amjad; Alkhdour, Saja; Alzuabi, Muayad A; Aker, Loai; Adeeb, Nimer; Massengale, Justin; Oskouian, Rod J; Shane Tubbs, R

    2017-03-01

    The intervertebral disc (IVD) is a joint unique in structure and functions. Lying between adjacent vertebrae, it provides both the primary support and the elasticity required for the spine to move stably. Various aspects of the IVD have long been studied by researchers seeking a better understanding of its dynamics, aging, and subsequent disorders. In this article, we review the surgical anatomy, imaging modalities, and molecular biology of the lumbar IVD. Clin. Anat. 30:251-266, 2017. © 2017 Wiley Periodicals, Inc.

  14. [Results of surgical treatment for the intervertebral disc protrusion within thoracic spine].

    PubMed

    Malawski, S; Lukawski, S

    1998-01-01

    Results of surgical treatment for intervertebral disc protrusion within thoracic spine in 4 cases are presented. Protrusion had caused spinal compression resulting in neurological impairment (plegia). There were 3 females and 1 male, all in their forties or fifties. Two cases are presented in details, with radiological investigations included. Lateral approach was used at surgery. Neurological deficits subsided completely in all cases. Follow-up ranged from 1-15 years, mean 8 years.

  15. Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy

    PubMed Central

    Ruzicka, Filip; Schmitz, Jonathan E.; James, Garth A.; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Lipina, Radim; Ahmed, Fahad S.; Alamin, Todd F.; Anand, Neel; Baird, John C.; Bhatia, Nitin; Demir-Deviren, Sibel; Eastlack, Robert K.; Fisher, Steve; Garfin, Steven R.; Gogia, Jaspaul S.; Gokaslan, Ziya L.; Kuo, Calvin C.; Lee, Yu-Po; Mavrommatis, Konstantinos; Michu, Elleni; Noskova, Hana; Raz, Assaf; Sana, Jiri; Shamie, A. Nick; Stewart, Philip S.; Stonemetz, Jerry L.; Wang, Jeffrey C.; Witham, Timothy F.; Coscia, Michael F.; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej

    2017-01-01

    Background In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. Methods Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. Results Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). Conclusions This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it

  16. A role for TNFα in intervertebral disc degeneration: A non-recoverable catabolic shift

    SciTech Connect

    Purmessur, D.; Walter, B.A.; Roughley, P.J.; Laudier, D.M.; Hecht, A.C.; Iatridis, James

    2013-03-29

    Highlights: ► TNFα induced catabolic changes similar to human intervertebral disc degeneration. ► The metabolic shift induced by TNFα was sustained following removal. ► TNFα induced changes suggestive of cell senescence without affecting cell viability. ► Interventions are required to stimulate anabolism and increase cell proliferation. -- Abstract: This study examines the effect of TNFα on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNFα contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using β-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNFα followed by 14 days in basal media. TNFα induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNFα increased aggrecan degradation products and suggests increased β-galactosidase staining at 21 days without any recovery. TNFα treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNFα significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in

  17. Thalamic Pain Misdiagnosed as Cervical Disc Herniation.

    PubMed

    Lim, Tae Ha; Choi, Soo Il; Yoo, Jee In; Choi, Young Soon; Lim, Young Su; Sang, Bo Hyun; Bang, Yun Sic; Kim, Young Uk

    2016-04-01

    Thalamic pain is a primary cause of central post-stroke pain (CPSP). Clinical symptoms vary depending on the location of the infarction and frequently accompany several pain symptoms. Therefore, correct diagnosis and proper examination are not easy. We report a case of CPSP due to a left acute thalamic infarction with central disc protrusion at C5-6. A 45-year-old-male patient experiencing a tingling sensation in his right arm was referred to our pain clinic under the diagnosis of cervical disc herniation. This patient also complained of right cramp-like abdominal pain. After further evaluations, he was diagnosed with an acute thalamic infarction. Therefore detailed history taking should be performed and examiners should always be aware of other symptoms that could suggest a more dangerous disease.

  18. Intervertebral Disc Degeneration and Ectopic Bone Formation in Apolipoprotein E Knockout Mice

    PubMed Central

    Zhang, Dawei; Jin, Li; Reames, Davis L.; Shen, Francis H.; Shimer, Adam L.; Li, Xudong

    2012-01-01

    Cardiovascular risk factors are known to be associated with intervertebral disc degeneration, but the underlying mechanism is still unclear. ApoE knockout (KO) mouse is a well-established model for arthrosclerosis. We hypothesize that ApoE may involve in maintaining disc health and ApoE KO mouse develops early disc degeneration. Discs of ApoE KO and wild-type (WT) mice were characterized with histological/immunological, biochemical, and real time RT-PCR assays. A comparison of the extracellular matrix production was also performed in disc cells. We demonstrated that ApoE was highly expressed in the endplates of WT discs and ectopic bone formed in the endplates of ApoE KO discs. Glycosaminoglycan content was decreased in both ApoE KO annulus fibrosus (AF) and nucleus pulpsous (NP) cells. Collagen levels were increased in AF and decreased in NP cells. Matrix metalloproteinases-3, 9, and 13 expression was increased which may partially explain the impaired matrix production. We also found increased collagen I, II, aggrecan and biglycan mRNA expressions in AF cells but decreased in NP cells. Apoptosis was increased in the ApoE KO NP tissue. These results suggest early disc degeneration changes in ApoE KO mice. ApoE, plus its importance to cardiovascular disease, may play a critical role in disc integrity and function. PMID:22915292

  19. Porcine Intervertebral Disc Repair Using Allogeneic Juvenile Articular Chondrocytes or Mesenchymal Stem Cells

    PubMed Central

    Acosta, Frank L.; Metz, Lionel; Adkisson, Huston Davis; Liu, Jane; Carruthers-Liebenberg, Ellen; Milliman, Curt; Maloney, Michael

    2011-01-01

    Tissue engineering strategies for intervertebral disc repair have focused on the use of autologous disc-derived chondrocytes. Difficulties with graft procurement, harvest site morbidity, and functionality, however, may limit the utility of this cell source. We used an in vivo porcine model to investigate allogeneic non-disc-derived chondrocytes and allogeneic mesenchymal stem cells (MSCs) for disc repair. After denucleation, lumbar discs were injected with either fibrin carrier alone, allogeneic juvenile chondrocytes (JCs), or allogeneic MSCs. Discs were harvested at 3, 6, and 12 months, and cell viability and functionality were assessed qualitatively and quantitatively. JC-treated discs demonstrated abundant cartilage formation at 3 months, and to a lesser extent at 6 and 12 months. For the carrier and MSC-treated groups, however, there was little evidence of proteoglycan matrix or residual notochordal/chondrocyte cells, but rather a type I/II collagen-enriched scar tissue. By contrast, JCs produced a type II collagen-rich matrix that was largely absent of type I collagen. Viable JCs were observed at all time points, whereas no evidence of viable MSCs was found. These data support the premise that committed chondrocytes are more appropriate for use in disc repair, as they are uniquely suited for survival in the ischemic disc microenvironment. PMID:21910592

  20. Difference in Energy Metabolism of Annulus Fibrosus and Nucleus Pulposus Cells of the Intervertebral Disc

    PubMed Central

    Salvatierra, Jessica Czamanski; Yuan, Tai Yi; Fernando, Hanan; Castillo, Andre; Gu, Wei Yong; Cheung, Herman S.; Huant, C.-Y. Charles

    2011-01-01

    Low back pain is associated with intervertebral disc degeneration. One of the main signs of degeneration is the inability to maintain extracellular matrix integrity. Extracellular matrix synthesis is closely related to production of adenosine triphosphate (i.e. energy) of the cells. The intervertebral disc is composed of two major anatomical regions: annulus fibrosus and nucleus pulposus, which are structurally and compositionally different, indicating that their cellular metabolisms may also be distinct. The objective of this study was to investigate energy metabolism of annulus fibrosus and nucleus pulposus cells with and without dynamic compression, and examine differences between the two cell types. Porcine annulus and nucleus tissues were harvested and enzymatically digested. Cells were isolated and embedded into agarose constructs. Dynamically loaded samples were subjected to a sinusoidal displacement at 2 Hz and 15% strain for 4 h. Energy metabolism of cells was analyzed by measuring adenosine triphosphate content and release, glucose consumption, and lactate/nitric oxide production. A comparison of those measurements between annulus and nucleus cells was conducted. Annulus and nucleus cells exhibited different metabolic pathways. Nucleus cells had higher adenosine triphosphate content with and without dynamic loading, while annulus cells had higher lactate production and glucose consumption. Compression increased adenosine triphosphate release from both cell types and increased energy production of annulus cells. Dynamic loading affected energy metabolism of intervertebral disc cells, with the effect being greater in annulus cells. PMID:21625336

  1. A 1-D model of the nonlinear dynamics of the human lumbar intervertebral disc

    NASA Astrophysics Data System (ADS)

    Marini, Giacomo; Huber, Gerd; Püschel, Klaus; Ferguson, Stephen J.

    2017-01-01

    Lumped parameter models of the spine have been developed to investigate its response to whole body vibration. However, these models assume the behaviour of the intervertebral disc to be linear-elastic. Recently, the authors have reported on the nonlinear dynamic behaviour of the human lumbar intervertebral disc. This response was shown to be dependent on the applied preload and amplitude of the stimuli. However, the mechanical properties of a standard linear elastic model are not dependent on the current deformation state of the system. The aim of this study was therefore to develop a model that is able to describe the axial, nonlinear quasi-static response and to predict the nonlinear dynamic characteristics of the disc. The ability to adapt the model to an individual disc's response was a specific focus of the study, with model validation performed against prior experimental data. The influence of the numerical parameters used in the simulations was investigated. The developed model exhibited an axial quasi-static and dynamic response, which agreed well with the corresponding experiments. However, the model needs further improvement to capture additional peculiar characteristics of the system dynamics, such as the change of mean point of oscillation exhibited by the specimens when oscillating in the region of nonlinear resonance. Reference time steps were identified for specific integration scheme. The study has demonstrated that taking into account the nonlinear-elastic behaviour typical of the intervertebral disc results in a predicted system oscillation much closer to the physiological response than that provided by linear-elastic models. For dynamic analysis, the use of standard linear-elastic models should be avoided, or restricted to study cases where the amplitude of the stimuli is relatively small.

  2. Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

    PubMed

    Tran, Cassie M; Shapiro, Irving M; Risbud, Makarand V

    2013-08-08

    Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration.

  3. Simulating the sensitivity of cell nutritive environment to composition changes within the intervertebral disc

    NASA Astrophysics Data System (ADS)

    Wills, C. Ruiz; Malandrino, A.; van Rijsbergen, MM.; Lacroix, D.; Ito, K.; Noailly, J.

    2016-05-01

    Altered nutrition in the intervertebral disc affects cell viability and can generate catabolic cascades contributing to extracellular matrix (ECM) degradation. Such degradation is expected to affect couplings between disc mechanics and nutrition, contributing to accelerate degenerative processes. However, the relation of ECM changes to major biophysical events within the loaded disc remains unclear. A L4-L5 disc finite element model including the nucleus (NP), annulus (AF) and endplates was used and coupled to a transport-cell viability model. Solute concentrations and cell viability were evaluated along the mid-sagittal plane path. A design of experiment (DOE) was performed. DOE parameters corresponded to AF and NP biochemical tissue measurements in discs with different degeneration grades. Cell viability was not affected by any parameter combinations defined. Nonetheless, the initial water content was the parameter that affected the most the solute contents, especially glucose. Calculations showed that altered NP composition could negatively affect AF cell nutrition. Results suggested that AF and NP tissue degeneration are not critical to nutrition-related cell viability at early-stage of disc degeneration. However, small ECM degenerative changes may alter significantly disc nutrition under mechanical loads. Coupling disc mechano-transport simulations and enzyme expression studies could allow identifying spatiotemporal sequences related to tissue catabolism.

  4. Calcification in the ovine intervertebral disc: a model of hydroxyapatite deposition disease

    PubMed Central

    Burkhardt, D.; Taylor, T. K. F.; Dillon, C. T.; Read, R.; Cake, M.; Little, C. B.

    2009-01-01

    The study design included a multidisciplinary examination of the mineral phase of ovine intervertebral disc calcifications. The objective of the study was to investigate the mineral phase and its mechanisms of formation/association with degeneration in a naturally occurring animal model of disc calcification. The aetiology of dystrophic disc calcification in adult humans is unknown, but occurs as a well-described clinical disorder with hydroxyapatite as the single mineral phase. Comparable but age-related pathology in the sheep could serve as a model for the human disorder. Lumbar intervertebral discs (n = 134) of adult sheep of age 6 years (n = 4), 8 years (n = 12) and 11 years (n = 2) were evaluated using radiography, morphology, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray powder diffraction, histology, immunohistology and proteoglycan analysis. Half of the 6-year, 84% of the 8-year and 86% of the 11-year-old discs had calcific deposits. These were not well delineated by plain radiography. They were either: (a) punctate deposits in the outer annulus, (b) diffuse deposits in the transitional zone or inner annulus fibrosus with occasional deposits in the nucleus, or (c) large deposits in the transitional zone extending variably into the nucleus. Their maximal incidence was in the lower lumbar discs (L4/5–L6/7) with no calcification seen in the lumbosacral or lower thoracic discs. All deposits were hydroxyapatite with large crystallite sizes (800–1,300 Å) compared to cortical bone (300–600 Å). No type X-collagen, osteopontin or osteonectin were detected in calcific deposits, although positive staining for bone sialoprotein was evident. Calcified discs had less proteoglycan of smaller hydrodynamic size than non-calcified discs. Disc calcification in ageing sheep is due to hydroxyapatite deposition. The variable, but large, crystal size and lack of protein markers indicate that this does not occur by

  5. Rheological and biological properties of a hydrogel support for cells intended for intervertebral disc repair

    PubMed Central

    2012-01-01

    Background Cell-based approaches towards restoration of prolapsed or degenerated intervertebral discs are hampered by a lack of measures for safe administration and placement of cell suspensions within a treated disc. In order to overcome these risks, a serum albumin-based hydrogel has been developed that polymerizes after injection and anchors the administered cell suspension within the tissue. Methods A hydrogel composed of chemically activated albumin crosslinked by polyethylene glycol spacers was produced. The visco-elastic gel properties were determined by rheological measurement. Human intervertebral disc cells were cultured in vitro and in vivo in the hydrogel and their phenotype was tested by reverse-transcriptase polymerase chain reaction. Matrix production and deposition was monitored by immuno-histology and by biochemical analysis of collagen and glycosaminoglycan deposition. Species specific in situ hybridization was performed to discriminate between cells of human and murine origin in xenotransplants. Results The reproducibility of the gel formation process could be demonstrated. The visco-elastic properties were not influenced by storage of gel components. In vitro and in vivo (subcutaneous implants in mice) evidence is presented for cellular differentiation and matrix deposition within the hydrogel for human intervertebral disc cells even for donor cells that have been expanded in primary monolayer culture, stored in liquid nitrogen and re-activated in secondary monolayer culture. Upon injection into the animals, gels formed spheres that lasted for the duration of the experiments (14 days). The expression of cartilage- and disc-specific mRNAs was maintained in hydrogels in vitro and in vivo, demonstrating the maintenance of a stable specific cellular phenotype, compared to monolayer cells. Significantly higher levels of hyaluronan synthase isozymes-2 and -3 mRNA suggest cell functionalities towards those needed for the support of the regeneration of

  6. Simulation of the Progression of Intervertebral Disc Degeneration due to Decreased Nutrition Supply

    PubMed Central

    Gu, Weiyong; Zhu, Qiaoqiao; Gao, Xin; Brown, Mark D.

    2014-01-01

    Study Design Simulate the progression of human disc degeneration. Objective The objective of this study was to quantitatively analyze and simulate the changes in cell density, nutrition level, proteoglycan content, water content, and volume change during human disc degeneration using a numerical method. Summary of Background Data Understanding the etiology and progression of intervertebral disc (IVD) degeneration is crucial for developing effective treatment strategies for IVD-degeneration related diseases. During tissue degeneration, the disc undergoes losses of cell viability and activities, changes in extracellular matrix composition and structure, and compromise of the tissue-level integrity and function, which is significantly influenced by the inter-coupled biological, chemical, electrical, and mechanical signals in the disc. Characterizing these signals in human discs in vivo is difficult. Methods A realistic 3D finite element model of the human IVD was developed based on biomechano-electrochemical continuum mixture theory. The theoretical framework and the constitutive relationships were all biophysics based. All the material properties were obtained from experimental results. The cell-mediated disc degeneration process caused by lowered nutrition levels at disc boundaries was simulated and validated by comparing with experimental results. Results Cell density reached equilibrium state in 30 days after reduced nutrition supply at the disc boundary, while the proteoglycan (PG) and water contents reached a new equilibrium state in 55 years. The simulated results for the distributions of PG and water contents within the disc were consistent with the results measured in the literature, except for the distribution of PG content in the sagittal direction. Conclusions Poor nutrition supply has a long-term effect on disc degeneration. PMID:25188596

  7. 75 FR 54345 - Determination of Regulatory Review Period for Purposes of Patent Extension; BRYAN CERVICAL DISC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    ... Patent Extension; BRYAN CERVICAL DISC SYSTEM AGENCY: Food and Drug Administration, HHS. ACTION: Notice... CERVICAL DISC SYSTEM and is publishing this notice of that determination as required by law. FDA has made... device BRYAN CERVICAL DISC SYSTEM. BRYAN CERVICAL DISC SYSTEM is indicated in skeletally mature...

  8. Total Disc Arthroplasty and Anterior Cervical Discectomy and Fusion in Cervical Spine: Competitive or Complimentary? Review of the Literature

    PubMed Central

    Jawahar, Ajay; Nunley, Pierce

    2012-01-01

    Anterior cervical discectomy and arthrodesis has come to represent standard of care for patients with persistent radicular and/or myelopathic symptoms that have failed to improve with conservative treatments. One potential complication of the procedure is the accelerated degeneration of the vertebrae and the intervertebral discs adjacent to the level fused and the effects of fusion on those levels. The concern that fusion may be a contributing factor to accelerated adjacent segment degeneration led to increased interest in cervical disc replacement after anterior decompressive surgery. Several studies analyzing the short-term outcomes of the disc replacement procedure have been published since then, and the pros and cons of both procedures continue to remain a topic of debate among the scientific community. The analysis of published literature and our own experience has convinced us that the overall longer-term clinical outcomes after anterior cervical discectomy and fusion (ACDF) and total disc replacement (TDR) in the general patient population are not significantly different in terms of symptomatic improvement, neurological improvement, and restoration to better quality of life. Age of the patients and number of affected levels may impact the outcomes and hence determine the choice of optimum procedure. To definitely compare the incidence of adjacent segment disease after these procedures, multi-institutional studies with predetermined and unanimously agreed upon clinical and radiological criteria should be undertaken and the results analyzed in an unbiased fashion. Until that time, it is reasonable to assume that ACDF as well as cervical TDR are both safe and effective procedures that may have outcome benefits in specific patient subgroups based upon demographics and clinical/radiological parameters at the time of surgery. PMID:24353966

  9. Glucosamine Supplementation Demonstrates a Negative Effect On Intervertebral Disc Matrix in an Animal Model of Disc Degeneration

    PubMed Central

    Jacobs, Lloydine; Vo, Nam; Coehlo, J. Paulo; Dong, Qing; Bechara, Bernard; Woods, Barrett; Hempen, Eric; Hartman, Robert; Preuss, Harry; Balk, Judith; Kang, James; Sowa, Gwendolyn

    2013-01-01

    Study Design Laboratory based controlled in vivo study Objective To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration Summary of Background Data Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A CDC report from 2009 reported that many patients are using glucosamine supplementation for low back pain (LBP), without significant evidence to support its use. Because disc degeneration is a major contributor of LBP, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration. Methods Eighteen skeletally mature New Zealand White rabbits were divided into four groups: control, annular puncture, glucosamine, and annular puncture+glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107mg/day (weight based equivalent to human 1500mg/day). Annular puncture surgery involved puncturing the annulus fibrosus (AF) of 3 lumbar discs with a 16G needle to induce degeneration. Serial MRIs were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan(GAG) content, relative gene expression measured by RT-PCR, and histological analyses. Results The MRI index and NP area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and GAG content. Gene expression was consistent with a detrimental effect on matrix. Conclusions These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, MRI, histology, and total proteoglycan is anti-anabolic. This raises concern over this commonly used supplement, and future research is needed to establish the clinical relevance of these

  10. Is cervical disc arthroplasty good for congenital cervical stenosis?

    PubMed

    Chang, Peng-Yuan; Chang, Hsuan-Kan; Wu, Jau-Ching; Huang, Wen-Cheng; Fay, Li-Yu; Tu, Tsung-Hsi; Wu, Ching-Lan; Cheng, Henrich

    2017-03-10

    OBJECTIVE Cervical disc arthroplasty (CDA) has been demonstrated to be as safe and effective as anterior cervical discectomy and fusion (ACDF) in the management of 1- and 2-level degenerative disc disease (DDD). However, there has been a lack of data to address the fundamental discrepancy between the two surgeries (CDA vs ACDF), and preservation versus elimination of motion, in the management of cervical myelopathy associated with congenital cervical stenosis (CCS). Although younger patients tend to benefit more from motion preservation, it is uncertain if CCS caused by multilevel DDD can be treated safely with CDA. METHODS Consecutive patients who underwent 3-level anterior cervical discectomy were retrospectively reviewed. Inclusion criteria were age less than 50 years, CCS (Pavlov ratio ≤ 0.82), symptomatic myelopathy correlated with DDD, and stenosis limited to 3 levels of the subaxial cervical (C3-7) spine. Exclusion criteria were ossification of the posterior longitudinal ligament, previous posterior decompression surgery (e.g., laminoplasty or laminectomy), osteoporosis, previous trauma, or other rheumatic diseases that might have caused the cervical myelopathy. All these patients who underwent 3-level discectomy were divided into 2 groups according to the strategies of management: preservation or elimination of motion (the hybrid-CDA group and the ACDF group). The hybrid-CDA group underwent 2-level CDA plus 1-level ACDF, whereas the ACDF group underwent 3-level ACDF. Clinical assessment was measured by the visual analog scales (VAS) for neck and arm pain, Japanese Orthopaedic Association (JOA) scores, and Nurick grades. Radiographic outcomes were measured using dynamic radiographs for evaluation of range of motion (ROM). RESULTS Thirty-seven patients, with a mean (± SD) age of 44.57 ± 5.10 years, were included in the final analysis. There was a male predominance in this series (78.4%, 29 male patients), and the mean follow-up duration was 2.37 ± 1

  11. Mechanical Characterization of the Human Lumbar Intervertebral Disc Subjected to Impact Loading Conditions

    NASA Astrophysics Data System (ADS)

    Jamison, David, IV

    Low back pain is a large and costly problem in the United States. Several working populations, such as miners, construction workers, forklift operators, and military personnel, have an increased risk and prevalence of low back pain compared to the general population. This is due to exposure to repeated, transient impact shocks, particularly while operating vehicles or other machinery. These shocks typically do not cause acute injury, but rather lead to pain and injury over time. The major focus in low back pain is often the intervertebral disc, due to its role as the major primary load-bearing component along the spinal column. The formation of a reliable standard for human lumbar disc exposure to repeated transient shock could potentially reduce injury risk for these working populations. The objective of this project, therefore, is to characterize the mechanical response of the lumbar intervertebral disc subjected to sub-traumatic impact loading conditions using both cadaveric and computational models, and to investigate the possible implications of this type of loading environment for low back pain. Axial, compressive impact loading events on Naval high speed boats were simulated in the laboratory and applied to human cadaveric specimen. Disc stiffness was higher and hysteresis was lower than quasi-static loading conditions. This indicates a shift in mechanical response when the disc is under impact loads and this behavior could be contributing to long-term back pain. Interstitial fluid loss and disc height changes were shown to affect disc impact mechanics in a creep study. Neutral zone increased, while energy dissipation and low-strain region stiffness decreased. This suggests that the disc has greater clinical instability during impact loading with progressive creep and fluid loss, indicating that time of day should be considered for working populations subjected to impact loads. A finite element model was developed and validated against cadaver specimen

  12. Static and dynamic compression application and removal on the intervertebral discs of growing rats.

    PubMed

    Ménard, Anne-Laure; Grimard, Guy; Massol, Elise; Londono, Irène; Moldovan, Florina; Villemure, Isabelle

    2016-02-01

    Fusionless implants are used to correct pediatric progressive spinal deformities, most of them spanning the intervertebral disc. This study aimed at investigating the effects of in vivo static versus dynamic compression application and removal on discs of growing rats. A microloading device applied compression. 48 immature rats (28 d.o.) were divided into two groups (43d, 53d). Each group included four subgroups: control (no surgery), sham (device installed without loading), static (0.2 MPa) and dynamic compressions (0.2 MPa ± 30% with 0.1 Hz). In 43d subgroups, compression was applied for 15 days. In 53d subgroups, compression was followed by 10 days without loading. Disc heights, nucleus/annulus volumetric proportions and nucleus proteoglycan contents were analyzed using one-way ANOVA and post-hoc Tukey comparisons (p < 0.05). Disc heights of 43d and 53d static and dynamic loading rats were lower than shams (p < 0.05). Volumetric proportions remained similar. At 43d, nucleus proteoglycan contents increased in both static and dynamic loading rats. However, at 53d, static loading rats had lower proteoglycan content than dynamic loading rats (p < 0.05). Disc structure is altered following static compression removal, but nucleus proteoglycan content remaining elevated in dynamic group. Dynamic fusionless implants would better preserve disc integrity.

  13. 1980 Volvo award in basic science. Proteoglycans in experimental intervertebral disc degeneration.

    PubMed

    Lipson, S J; Muir, H

    1981-01-01

    An animal model of intervertebral disc degeneration induced surgically by ventral nuclear herniation in the rabbit produces morphologic changes of disc degeneration. Histologic characteristics and proteoglycan changes have been studied at various times after herniation. After injury, there was metaplasia into fibrocartilage originating from the cells along the margins of the annular wound, with proliferation of cells changing almost the entire disc space into fibrocartilage. A vertebral osteophyte occurred through an endochondral ossification sequence. Aggregating proteoglycans had two periods of repletion in the early course of degeneration. The water content of the disc was rapidly but only transiently restored in the first two days after herniation, whilst the changes in the total proteoglycan content of the disc paralleled these changes. Hyaluronic acid content decreased rapidly after herniation, but the size of the proteoglycan monomers did not change with degeneration. It is suggested that loss of confined fluid mechanics signals an abortive repair attempt rather than that of biochemical changes in proteoglycans initiate disc degeneration.

  14. Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs

    PubMed Central

    Nasto, Luigi A.; Wang, Dong; Robinson, Andria R.; Clauson, Cheryl L.; Ngo, Kevin; Dong, Qing; Roughley, Peter; Epperly, Michael; Huq, Saiful M.; Pola, Enrico; Sowa, Gwendolyn; Robbins, Paul D.; Kang, James; Niedernhofer, Laura J.; Vo, Nam V.

    2013-01-01

    Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1−/Δ mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3-5x in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments were significantly increased. Additionally, new PG synthesis was reduced 2-3x in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1−/Δ mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD. PMID:23262094

  15. Loading-Induced Heat-Shock Response in Bovine Intervertebral Disc Organ Culture

    PubMed Central

    Chooi, Wai Hon; Chan, Samantha Chun Wai; Gantenbein, Benjamin; Chan, Barbara Pui

    2016-01-01

    Mechanical loading has been shown to affect cell viability and matrix maintenance in the intervertebral disc (IVD) but there is no investigation on how cells survive mechanical stress and whether the IVD cells perceive mechanical loading as stress and respond by expression of heat shock proteins. This study investigates the stress response in the IVD in response to compressive loading. Bovine caudal disc organ culture was used to study the effect of physiological range static loading and dynamic loading. Cell activity, gene expression and immunofluorescence staining were used to analyze the cell response. Cell activity and cytoskeleton of the cells did not change significantly after loading. In gene expression analysis, significant up-regulation of heat shock protein-70 (HSP70) was observed in nucleus pulposus after two hours of loading. However, the expression of the matrix remodeling genes did not change significantly after loading. Similarly, expressions of stress response and matrix remodeling genes changed with application and removal of the dynamic loading. The results suggest that stress response was induced by physiological range loading without significantly changing cell activity and upregulating matrix remodeling. This study provides direct evidence on loading induced stress response in IVD cells and contributes to our understanding in the mechanoregulation of intervertebral disc cells. PMID:27580124

  16. Method for obtaining simple shear material properties of the intervertebral disc under high strain rates.

    PubMed

    Ott, Kyle A; Armiger, Robert S; Wickwire, Alexis C; Carneal, Catherine M; Trexler, Morgana M; Lennon, Andrew M; Zhang, Jiangyue; Merkle, Andrew C

    2012-01-01

    Predicting spinal injury under high rates of vertical loading is of interest, but the success of computational models in modeling this type of loading scenario is highly dependent on the material models employed. Understanding the response of these biological materials at high strain rates is critical to accurately model mechanical response of tissue and predict injury. While data exists at lower strain rates, there is a lack of the high strain rate material data that are needed to develop constitutive models. The Split Hopkinson Pressure Bar (SHPB) has been used for many years to obtain properties of various materials at high strain rates. However, this apparatus has mainly been used for characterizing metals and ceramics and is difficult to apply to softer materials such as biological tissue. Recently, studies have shown that modifications to the traditional SHPB setup allow for the successful characterization of mechanical properties of biological materials at strain rates and peak strain values that exceed alternate soft tissue testing techniques. In this paper, the previously-reported modified SHPB technique is applied to characterize human intervertebral disc material under simple shear. The strain rates achieved range from 5 to 250 strain s-1. The results demonstrate the sensitivity to the disc composition and structure, with the nucleus pulposus and annulus fibrosus exhibiting different behavior under shear loading. Shear tangent moduli are approximated at varying strain levels from 5 to 20% strain. This data and technique facilitates determination of mechanical properties of intervertebral disc materials under shear loading, for eventual use in constitutive models.

  17. Temperature Distributions of the Lumbar Intervertebral Disc during Laser Annuloplasty : A Cadaveric Study

    PubMed Central

    Lee, Min Hyung; Hong, Jae Taek; Sung, Jae Hoon; Lee, Sang Won; Kim, Daniel H.

    2016-01-01

    Objective Low back pain, caused intervertebral disc degeneration has been treated by thermal annuloplasty procedure, which is a non-surgical treatement. The theoretical backgrounds of the annuloplasty are thermal destruct of nociceptor and denaturization of collagen fiber to induce contraction, to shrink annulus and thus enhancing stability. This study is about temperature and its distribution during thermal annuloplasty using 1414 nm Nd : YAG laser. Methods Thermal annuloplasty was performed on fresh human cadaveric lumbar spine with 20 intact intervertebral discs in a 37℃ circulating water bath using newly developed 1414 nm Nd : YAG laser. Five thermocouples were attached to different locations on the disc, and at the same time, temperature during annuloplasty was measured and analyzed. Results Thermal probe's temperature was higher in locations closer to laser fiber tip and on lateral locations, rather than the in depth locations. In accordance with the laser fiber tip and the depth, temperatures above 45.0℃ was measured in 3.0 mm depth which trigger nociceptive ablation in 16 levels (80%), in accordance with the laser fiber end tip and laterality, every measurement had above 45.0℃, and also was measured temperature over 60.0℃, which can trigger collagen denaturation at 16 levels (80%). Conclusion When thermal annuloplasty is needed in a selective lesion, annuloplasty using a 1414 nm Nd : YAG laser can be one of the treatment options. PMID:27847567

  18. Paraspinal muscle activation in accordance with mechanoreceptors in the intervertebral discs.

    PubMed

    Kim, Young Eun; Choi, Hae Won

    2013-02-01

    Paraspinal muscle forces were derived computationally based on the hypothesis that the intervertebral disc has a transducer function and the muscle is activated according to a sensor-driving control mechanism. A three-dimensional finite element model of the musculoskeletal system, which consisted of a detailed whole lumbar spine, pelvis, simplified trunk model, and muscles, was developed and combined with an optimization technique to calculate muscle forces in isometric forward flexed and erect standing postures. Minimization of deviations in the nucleus pressure and averaged tensile stress in the annulus fibers at five discs was used for muscle force calculations. The results indicated that all the muscles were properly activated to maintain posture and stabilize the lumbar spine. The nucleus pressure difference was decreased during the iterative calculations and its resulting value at the L4/L5 level was consistent with in vivo measurements. Muscle activation produced vertebra motion, which resulted in a relatively uniform stress distribution in the intervertebral discs. This can minimize the risk of injury at a specific level and increase the ability of the spine to sustain a load.

  19. Graph cuts with invariant object-interaction priors: application to intervertebral disc segmentation.

    PubMed

    Ben Ayed, Ismail; Punithakumar, Kumaradevan; Garvin, Gregory; Romano, Walter; Li, Shuo

    2011-01-01

    This study investigates novel object-interaction priors for graph cut image segmentation with application to intervertebral disc delineation in magnetic resonance (MR) lumbar spine images. The algorithm optimizes an original cost function which constrains the solution with learned prior knowledge about the geometric interactions between different objects in the image. Based on a global measure of similarity between distributions, the proposed priors are intrinsically invariant with respect to translation and rotation. We further introduce a scale variable from which we derive an original fixed-point equation (FPE), thereby achieving scale-invariance with only few fast computations. The proposed priors relax the need of costly pose estimation (or registration) procedures and large training sets (we used a single subject for training), and can tolerate shape deformations, unlike template-based priors. Our formulation leads to an NP-hard problem which does not afford a form directly amenable to graph cut optimization. We proceeded to a relaxation of the problem via an auxiliary function, thereby obtaining a nearly real-time solution with few graph cuts. Quantitative evaluations over 60 intervertebral discs acquired from 10 subjects demonstrated that the proposed algorithm yields a high correlation with independent manual segmentations by an expert. We further demonstrate experimentally the invariance of the proposed geometric attributes. This supports the fact that a single subject is sufficient for training our algorithm, and confirms the relevance of the proposed priors to disc segmentation.

  20. A prospective morphological study of facet joint integrity following intervertebral disc replacement with the CHARITE Artificial Disc.

    PubMed

    Trouillier, Hans; Kern, P; Refior, H J; Müller-Gerbl, M

    2006-02-01

    In degenerative disc disease (DDD), increased loading in the posterior column increases facet joint subchondral bone density and may lead to facet joint degeneration. While spinal fusion is commonly used to treat patients with symptomatic DDD, increased stress at the levels adjacent to fusion may accelerate facet joint and adjacent segment degeneration. Artificial disc replacements have been developed as an alternative to fusion. In this prospective study, the effects of disc replacement with the CHARITE Artificial Disc on facet joint loading and integrity were evaluated. Thirteen patients aged <50 years with symptomatic DDD were recruited. Computed tomography (CT) osteoabsorptiometry was performed prior to the implantation of the CHARITE Artificial Disc and six months after. With this technique, increases or decreases in facet joint loading and integrity are indicated by corresponding changes in subchondral bone density. Changes in the distribution of load alter the distribution of the areas of maximum bone density. Clinical outcome was also assessed at pre-operative and 6 and 12 month post-operative visits using the Visual Analogue Scale back and leg pain scores, the Oswestry Disability Index and the Short Form-36 (SF-36) questionnaire. The height of the intervertebral space at the operated level was monitored by lateral X-ray. Subchondral bone density was evaluated in the facet joints of all 13 patients at the operated level, 12 patients at the level above the operated segment, and five patients at the level below the operated segment. Quantitative measurements revealed no significant increases (> or =3%) in subchondral bone density of the facet joints at any level in any patient. Significant decreases (> or =3%) in subchondral bone density were measured at the operated level in 10/13 patients, at the level above the operated segment in 6/12 patients, and at the level below the operated segment in 3/5 patients. There were no changes in the distribution of the

  1. A Structurally and Functionally Biomimetic Biphasic Scaffold for Intervertebral Disc Tissue Engineering

    PubMed Central

    Choy, Andrew Tsz Hang; Chan, Barbara Pui

    2015-01-01

    Tissue engineering offers high hopes for the treatment of intervertebral disc (IVD) degeneration. Whereas scaffolds of the disc nucleus and annulus have been extensively studied, a truly biomimetic and mechanically functional biphasic scaffold using naturally occurring extracellular matrix is yet to be developed. Here, a biphasic scaffold was fabricated with collagen and glycosaminoglycans (GAGs), two of the most abundant extracellular matrix components in the IVD. Following fabrication, the scaffold was characterized and benchmarked against native disc. The biphasic scaffold was composed of a collagen-GAG co-precipitate making up the nucleus pulposus-like core, and this was encapsulated in multiple lamellae of photochemically crosslinked collagen membranes comprising the annulus fibrosus-like lamellae. On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc. The annulus-independent nature of disc height recovery suggests that the fluid replacement function of the engineered nucleus pulposus core might mimic this hitherto unique feature of native disc. Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery. However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs. This study contributes to the rationalized design and development of a biomimetic and mechanically viable biphasic scaffold for IVD tissue engineering. PMID:26115332

  2. The Effects of Glucosamine Sulfate on Intervertebral Disc Annulus Fibrosus Cells in Vitro

    PubMed Central

    Sowa, Gwendolyn; Coelho, J. Paulo; Jacobs, Lloydine; Komperda, Kasey; Sherry, Nora; Vo, Nam; Preuss, Harry; Balk, Judith; Kang, Jame

    2014-01-01

    Background context Glucosamine has gained widespread use among patients, despite inconclusive efficacy data. Inconsistency in the clinical literature may be related to lack of understanding of the effects of glucosamine on the intervertebral disc, and therefore, improper patient selection. Purpose The goal of our study was to investigate the effects of glucosamine on intervertebral disc cells in vitro under the physiological conditions of inflammation and mechanical loading. Study Design Controlled in vitro laboratory setting Methods Intervertebral disc cells isolated from the rabbit annulus fibrosus were exposed to glucosamine sulfate in the presence and absence of interleukin-1beta and tensile strain. Outcome measures included gene expression, measurement of total glycosaminoglycans, new proteoglycan synthesis, prostaglandin E2 production, and matrix metalloproteinase activity. The study was funded by NIH/NCCAM and the authors have no conflicts of interest. Results Under conditions of inflammatory stimulation alone, glucosamine demonstrated a dose dependent effect in decreasing inflammatory and catabolic mediators and increasing anabolic genes. However, under conditions of mechanical stimulation, although inflammatory gene expression was decreased, PGE2 was not. In addition, MMP-3 gene expression was increased and aggrecan expression decreased, both of which would have a detrimental effect on matrix homeostasis. Consistent with this, measurement of total glycosaminoglycans and new proteoglycan synthesis demonstrated detrimental effects of glucosamine under all conditions tested. Conclusions These results may in part help to explain the conflicting reports of efficacy, as there is biological plausibility for a therapeutic effect under conditions of predominate inflammation, but not under conditions where mechanical loading is present or in which matrix synthesis is needed. PMID:24361347

  3. CT and MRI Determination of Intermuscular Space within Lumbar Paraspinal Muscles at Different Intervertebral Disc Levels

    PubMed Central

    Wang, Shidong; Zhang, Yu; Han, Hui; Zheng, Dengquan; Ding, Zihai; Wong, Kelvin K. L.

    2015-01-01

    Background Recognition of the intermuscular spaces within lumbar paraspinal muscles is critically important for using the paramedian muscle-splitting approach to the lumbar spine. As such, it is important to determine the intermuscular spaces within the lumbar paraspinal muscles by utilizing modern medical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI). Methods A total of 30 adult cadavers were studied by sectional anatomic dissection, and 60 patients were examined using CT (16 slices, 3-mm thickness, 3-mm intersection gap, n = 30) and MRI (3.0T, T2-WI, 5-mm thickness, 1-mm intersection gap, n = 30). The distances between the midline and the superficial points of the intermuscular spaces at different intervertebral disc levels were measured. Results Based on study of our cadavers, the mean distances from the midline to the intermuscular space between multifidus and longissimus, from intervertebral disc levels L1–L2 to L5–S1, were 0.9, 1.1, 1.7, 3.0, and 3.5 cm, respectively. Compared with the upper levels (L1–L3), the superficial location at the lower level (L4–S1) is more laterally to the midline (P<0.05). The intermuscular space between sacrospinalis and quadratus lumborum, and that between longissimus and iliocostalis did not exist at L4–S1. The intermuscular spaces in patients also varied at different levels of the lumbar spine showing a low discontinuous density in CT and a high signal in MRI. There were no significant differences between the observations in cadavers and those made using CT and MRI. Conclusion The intermuscular spaces within the paraspinal muscles vary at different intervertebral disc levels. Preoperative CT and MRI can facilitate selection of the muscle-splitting approach to the lumbar spine. This paper demonstrates the efficacy of medical imaging techniques in surgical planning. PMID:26458269

  4. High incidence of persistence of sacral and coccygeal intervertebral discs in South Indians – a cadaveric study

    PubMed Central

    Satheesha Nayak, B; Ashwini Aithal, P; Kumar, Naveen; George, Bincy M; Deepthinath, R; Shetty, Surekha D

    2016-01-01

    The sacrum, by virtue of its anatomic location plays a key role in providing stability and strength to the pelvis. Presence of intervertebral discs in sacrum and coccyx is rare. Knowledge of its variations is of utmost importance to surgeons and radiologists. The current study focused on the presence of intervertebral discs between the sacral and coccygeal vertebrae in south Indian cadaveric pelvises. We observed 56 adult pelvises of which, 34 (61%) pelvises showed the presence of intervertebral discs between the sacral vertebrae and between the coccygeal vertebrae, while 22 (39%) pelvises did not have the intervertebral discs either in the sacrum or the coccyx. We also found that most of the specimens had discs between S1 and S2 vertebrae (39%), followed by, between S4 and S5 (18%), between S2–S3 (14%) and least being between S3–S4 (13%). In the coccyx it was found that 7% of pelvises had disc between Co1-Co2, 4% of them had between Co2-Co3 and 4% had between Co3-Co4. Knowledge regarding such anatomic variations in the sacro-coccygeal region is important to note because they require alterations in various instrumentation procedures involving the sacrum. PMID:27385838

  5. Artificial Discs for Lumbar and Cervical Degenerative Disc Disease –Update

    PubMed Central

    2006-01-01

    Executive Summary Objective To assess the safety and efficacy of artificial disc replacement (ADR) technology for degenerative disc disease (DDD). Clinical Need Degenerative disc disease is the term used to describe the deterioration of 1 or more intervertebral discs of the spine. The prevalence of DDD is roughly described in proportion to age such that 40% of people aged 40 years have DDD, increasing to 80% among those aged 80 years or older. Low back pain is a common symptom of lumbar DDD; neck and arm pain are common symptoms of cervical DDD. Nonsurgical treatments can be used to relieve pain and minimize disability associated with DDD. However, it is estimated that about 10% to 20% of people with lumbar DDD and up to 30% with cervical DDD will be unresponsive to nonsurgical treatments. In these cases, surgical treatment is considered. Spinal fusion (arthrodesis) is the process of fusing or joining 2 bones and is considered the surgical gold standard for DDD. Artificial disc replacement is the replacement of the degenerated intervertebral disc with an artificial disc in people with DDD of the lumbar or cervical spine that has been unresponsive to nonsurgical treatments for at least 6 months. Unlike spinal fusion, ADR preserves movement of the spine, which is thought to reduce or prevent the development of adjacent segment degeneration. Additionally, a bone graft is not required for ADR, and this alleviates complications, including bone graft donor site pain and pseudoarthrosis. It is estimated that about 5% of patients who require surgery for DDD will be candidates for ADR. Review Strategy The Medical Advisory Secretariat conducted a computerized search of the literature published between 2003 and September 2005 to answer the following questions: What is the effectiveness of ADR in people with DDD of the lumbar or cervical regions of the spine compared with spinal fusion surgery? Does an artificial disc reduce the incidence of adjacent segment degeneration (ASD

  6. Concomitance of fibromyalgia syndrome and cervical disc herniation

    PubMed Central

    Güler, Mustafa; Aydın, Teoman; Akgöl, Erdal; Taşpınar, Özgür

    2015-01-01

    [Purpose] Fibromyalgia syndrome (FMS) and cervical disc herniation (CDH) are a common diseases commonly encountered in physical therapy clinics. There are also patients who have both of these diseases. In this study we aim to investigated whether FMS is a risk factor for cervical disc herniation and the frequency of their coincident occurrence. [Subjects and Methods] Thirty-five patients having a primary FMS diagnosis according to the American Rheumatism Association criteria are taken into consideration and a control group were the subjects of this study. The two groups were compared with respect to cervical disc hernia using cervical region MRI. [Results] The distribution of disc hernia of 6 fibromyalgia patients who had cervical discopathy was: 16.6% C2–3, 16.6% C5–6, 16.6% C6–7, 33.3% C4–5, C5–6 (two levels in two patients) and 16.6% C4–5, C5–6, C7–1 (three levels in one patient) . The herniation directions were given as: central in 5 levels, right paramedian in 1 level, and left paramedian disc hernia in 1 level. There were 4 cervical disk hernia in the control group. The herniation direction were central in two, right paramedian in one, and left paramedian in one patient. [Conclusion] In this study, the existence of cervical disc herniation in fibromyalgia patients was found to be not different from the normal population. PMID:25931731

  7. [Research advances of three-dimension printing technology in vertebrae and intervertebral disc tissue engineering].

    PubMed

    Yang, Zechuan; Li, Chunde; Sun, Haolin

    2016-03-01

    Three-dimensional (3D) printing technology is characterized by "inside-out" stack manufacturing. Compared with conventional technologies, 3D printing has the advantage of personalization and precision. Therefore, the shape and internal structure of the scaffolds made by 3D printing technology are highly biomimetic. Besides, 3D bioprinting can precisely deposit the biomaterials, seeding cells and cytokines at the same time, which is a breakthrough in printing technique and material science. With the development of 3D printing, it will make great contributions to the reconstruction of vertebrae and intervertebral disc in the future.

  8. Is a purpose of REM sleep atonia to help regenerate intervertebral disc volumetric loss?

    PubMed Central

    Fryer, Jerome CJ

    2009-01-01

    The nature of atonia in sleep continues to be enigmatic. This article discusses a new hypothesis for complete core muscle relaxation in REM sleep, suggesting a bottom-up recuperative perspective. That is, does the atonia in REM sleep provide a utility to help restore the mechanobiology and respective diurnal intervertebral disc hydraulic loss? By combining the effects of gravity with current compressive concepts in spinal stability, this article looks at vertebral approximation as a deleterious experience with an intrinsic biological need to keep vertebrae separated. Methods using polysomnography and recumbent MRI are discussed. PMID:19123938

  9. Effect of calcitonin pretreatment on naturally occurring intervertebral disc degeneration in guinea pig

    PubMed Central

    Jiang, Xiaohua; Tian, Faming; Wang, Wenya; Yan, Jinyin; Liu, Huanjiang; Liu, Binbin; Song, Huiping; Zhang, Yingze; Shen, Yong; Zhang, Liu

    2015-01-01

    Introduction: Our previous study suggested protective effects of calcitonin (CT) on experimental osteoarthritis. The aim of the present study was to provide evidence of whether CT pretreatment could prevent naturally occurring intervertebral disc degeneration in guinea pigs. Methods: Forty-two 3 months old female guinea pigs were randomly assigned into 2 groups as follows: Twenty-four were treated by normal saline as control group and sacrificed at 3, 6, 9 and 12 months of age (6 animals at each time point), the other 18 were received salmon CT (8 ug/kg/day, everyday) treatment at 3 months of age and sacrificed at the age of 6, 9 and 12 months respectively. Van Gieson stain and the histological score were used to identify the histological changes of the lumbar intervertebral discs. The disc height and vertebral body height were measured. Immunohistochemistry measurements for glycosaminoglycan, type II collagen, and matrix metalloprotease (MMP)-1 expressions were performed. Bone quality and microstructural changes in the L3-6 lumbar vertebral bodies were assessed by bone mineral density (BMD), micro-CT analysis and biomechanical testing. Results: Histological analysis indicated significantly higher disc degeneration scores in 9-month-old guinea pigs in comparison with younger animals, and grew higher with increasing age. CT treatment significantly reduced the histological score, and increased the disc height and the ratio to vertebral body height in 12 months old animals, as well as upregulated the glycosaminoglycan, type II collagen and inhibited the MMP-1 expression. Micro-CT analysis showed decreased percent bone volume (BV/TV) and increased trabecular separation (Tb.Sp), structural model index (SMI) in 12 months old animals in comparison with the younger animals. Markedly increased BV/TV and decreased Tb.Sp were observed in CT treated animals when compared with control animals. The biomechanical properties including maximum load, maximum stress, yield stress and

  10. Selection of the appropriate surgical approach for intervertebral disc disease.

    PubMed

    Bitetto, W V; Brown, N O

    1989-01-01

    In no other area of veterinary surgery is the selection and performance of the appropriate surgical approach more important than neurosurgery. An adequate, atraumatic, and anatomically sound exposure is an important part of the battle in most orthopaedic procedures and is an even more important consideration when related to neurosurgery. The delicate and often unforgiving nature of the tissue involved dictates that careful planning and attention to detail become high priority concerns for the veterinary neurosurgeon. Most veterinarians recommend surgery for dogs with severe impairment, recurrent disease, and progressively deteriorating neurologic signs. Difficulties remain in the timing of surgery and in the choice of what surgical approach is most appropriate for the neurologically impaired dog in question. Surgical approaches in the cervical region include ventral and dorsal. In the thoracolumbar spine, either dorsal or dorsolateral approaches are used. In the lumbosacral region, a dorsal approach is preferred. The objective of this chapter will be to compare and contrast each of these approaches and to guide the reader in the selection of the appropriate approach for each patient.

  11. 1980 Volvo award winner in basic science. Nutritional pathways of the intervertebral disc. An experimental study using hydrogen washout technique.

    PubMed

    Ogata, K; Whiteside, L A

    1981-01-01

    The pathways of material transfer to the intervertebral disc were studied in adult dogs by measuring diffusion of hydrogen molecules in the nucleus pulposus before and after disruption of the route through the annulus fibrosus and before and after disruption of the end-plate route. The interfaces was only in the central two-thirds of one side, caused significantly greater decrease in the rate of hydrogen washout than the disruption of the annulus route. Histologically, the bone-cartilage interface was frequently perforated by marrow cavity and vascular buds. These findings suggest that the end-plate route is a major pathway for material transfer to the intervertebral disc.

  12. LASER BIOLOGY AND MEDICINE: Effect of repetitive laser pulses on the electrical conductivity of intervertebral disc tissue

    NASA Astrophysics Data System (ADS)

    Omel'chenko, A. I.; Sobol', E. N.

    2009-03-01

    The thermomechanical effect of 1.56-μm fibre laser pulses on intervertebral disc cartilage has been studied using ac conductivity measurements with coaxial electrodes integrated with an optical fibre for laser radiation delivery to the tissue. The observed time dependences of tissue conductivity can be interpreted in terms of hydraulic effects and thermomechanical changes in tissue structure. The laserinduced changes in the electrical parameters of the tissue are shown to correlate with the structural changes, which were visualised using shadowgraph imaging. Local ac conductivity measurements in the bulk of tissue can be used to develop a diagnostic/monitoring system for laser regeneration of intervertebral discs.

  13. Discover cervical disc arthroplasty versus anterior cervical discectomy and fusion in symptomatic cervical disc diseases: A meta-analysis

    PubMed Central

    Shangguan, Lei; Ning, Guang-Zhi; Tang, Yu; Wang, Zhe; Luo, Zhuo-Jing; Zhou, Yue

    2017-01-01

    Objective Symptomatic cervical disc disease (SCDD) is a common degenerative disease, and Discover artificial cervical disc, a new-generation nonconstrained artificial disk, has been developed and performed gradually to treat it. We performed this meta-analysis to compare the efficacy and safety between Discover cervical disc arthroplasty (DCDA) and anterior cervical discectomy and fusion (ACDF) for SCDD. Methods An exhaustive literature search of PubMed, EMBASE, and the Cochrane Library was conducted to identify randomized controlled trials that compared DCDA with ACDF for patients suffering SCDD. A random-effect model was used. Results were reported as standardized mean difference or risk ratio with 95% confidence interval. Results Of 33 articles identified, six studies were included. Compared with ACDF, DCDA demonstrated shorter operation time (P < 0.0001), and better range of motion (ROM) at the operative level (P < 0.00001). But no significant differences were observed in blood loss, neck disability index (NDI) scores, neck and arm pain scores, Japanese orthopaedic association (JOA) scores, secondary surgery procedures and adverse events (P > 0.05). Subgroup analyses did not demonstrated significant differences. Conclusion In conclusion, DCDA presented shorter operation time, and better ROM at the operative level. However, no significant differences were observed in blood loss, NDI scores, neck and arm pain scores, JOA scores, secondary surgery procedures and adverse events between the two groups. Additionally, more studies of high quality with mid- to long-term follow-up are required in future. PMID:28358860

  14. Multipoint determination of pressure-volume curves in human intervertebral discs.

    PubMed Central

    Ranu, H S

    1993-01-01

    To gain further insight into the biomechanics of the human intervertebral disc and to determine a potential mechanism for causation and relief of symptoms related to a herniated disc, the pressure-volume relation was determined within the nucleus pulposus. Pressure was measured continuously within the nucleus pulposus in 17 intact lumbar discs from human cadavers by means of a miniature strain gauge at the tip of a size 4 French (1.3 mm) catheter inserted into the nucleus pulposus. The volume of the nucleus pulposus was increased at the slow, continuous rate of 0.034 ml/min by the pump regulated infusion of saline coloured with methylene blue. In 12 unloaded discs, nucleus pulposus pressure rose in a linear fashion (linear r = 0.96) from an initial mean pressure of 174 (SD 81) kPa. The mean rate of pressure rise was 327 (SD 109) kPa/ml volume increase. The peak pressure measured was 550 kPa; this was slightly higher than the capability of the transducer. Similar linear relations were obtained during infusion of saline into five vertically loaded discs fixed at the deformation produced by a 9.1 kg weight. The data define the pressure-volume relation within the disc and show that the nucleus pulposus, surrounded by the relatively inelastic annulus and the solid vertebral end plates, has the properties of a tight hydraulic space in which a large pressure rise will regularly result from a small increase in volume. Presumably the opposite is also true. The data may provide a biomechanical basis for the physiological variation in symptoms related to the disc, and for any benefits obtained from interventions designed to remove disc tissue. PMID:8447694

  15. Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study

    PubMed Central

    Elmasry, Shady; Asfour, Shihab; de Rivero Vaccari, Juan Pablo; Travascio, Francesco

    2015-01-01

    Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking. PMID:26301590

  16. Analysis of cell viability in intervertebral disc: Effect of endplate permeability on cell population.

    PubMed

    Shirazi-Adl, A; Taheri, M; Urban, J P G

    2010-05-07

    Responsible for making and maintaining the extracellular matrix, the cells of intervertebral discs are supplied with essential nutrients by diffusion from the blood supply through mainly the cartilaginous endplates (CEPs) and disc tissue. Decrease in transport rate and increase in cellular activity may adversely disturb the intricate supply-demand balance leading ultimately to cell death and disc degeneration. The present numerical study aimed to introduce for the first time cell viability criteria into nonlinear coupled nutrition transport equations thereby evaluating the dynamic nutritional processes governing viable cell population and concentrations of oxygen, glucose and lactic acid in the disc as CEP exchange area dropped from a fully permeable condition to an almost impermeable one. A uniaxial model of an in vitro cell culture analogue of the disc is first employed to examine and validate cell viability criteria. An axisymmetric model of the disc with four distinct regions was subsequently used to investigate the survival of cells at different CEP exchange areas. In agreement with measurements, predictions of the diffusion chamber model demonstrated substantial cell death as essential nutrient concentrations fell to levels too low to support cells. Cells died away from the nutrient supply and at higher cell densities. In the disc model, the nucleus region being farthest away from supply sources was most affected; cell death initiated first as CEP exchange area dropped below approximately 40% and continued exponentially thereafter to depletion as CEP calcified further. In cases with loss of endplate permeability and/or disruptions therein, as well as changes in geometry and fall in diffusivity associated with fluid outflow, the nutrient concentrations could fall to levels inadequate to maintain cellular activity or viability, resulting in cell death and disc degeneration.

  17. Ultrastructure of inclusion bodies in annulus cells in the degenerating human intervertebral disc.

    PubMed

    Gruber, H E; Hanley, E N

    2009-06-01

    The rough endoplasmic reticulum (rER) of the cell has an architectural editing function that checks whether protein structure and three-dimensional assembly have occurred properly prior to export of newly synthesized material out of the cell. If these have been faulty, the material is retained within the rER as an inclusion body. Inclusion bodies have been identified previously in chondrocytes and osteoblasts in chondrodysplasias and osteogenesis imperfecta. Inclusion bodies in intervertebral disc cells, however, have only recently been recognized. Our objectives were to use transmission electron microscopy to analyze more fully inclusion bodies in the annulus pulposus and to study the extracellular matrix (ECM) surrounding cells containing inclusion bodies. ECM frequently encapsulated cells with inclusion bodies, and commonly contained prominent banded aggregates of Type VI collagen. Inclusion body material had several morphologies, including relatively smooth, homogeneous material, or a rougher, less homogeneous feature. Such findings expand our knowledge of the fine structure of the human disc cell and ECM during disc degeneration, and indicate the potential utility of ultrastructural identification of discs with intracellular inclusion bodies as a screening method for molecular studies directed toward identification of defective gene products in degenerating discs.

  18. Dose-Dependent Response of Tissue-Engineered Intervertebral Discs to Dynamic Unconfined Compressive Loading

    PubMed Central

    Hudson, Katherine D.; Mozia, Robert I.

    2015-01-01

    Because of the limitations of current surgical methods in the treatment of degenerative disc disease, tissue-engineered intervertebral discs (TE-IVDs) have become an important target. This study investigated the biochemical and mechanical responses of composite TE-IVDs to dynamic unconfined compression. TE-IVDs were manufactured by floating an injection molded alginate nucleus pulposus (NP) in a type I collagen annulus fibrosus (AF) that was allowed to contract for 2 weeks before loading. The discs were mechanically stimulated at a range of strain amplitude (1–10%) for 2 weeks with a duty cycle of 1 h on–1 h off–1 h on before being evaluated for their biochemical and mechanical properties. Mechanical loading increased all properties in a dose-dependent manner. Glycosaminoglycans (GAGs) increased between 2.8 and 2.2 fold in the AF and NP regions, respectively, whereas the hydroxyproline content increased between 1.2 and 1.8 fold. The discs also experienced a 2-fold increase in the equilibrium modulus and a 4.3-fold increase in the instantaneous modulus. Full effects for all properties were seen by 5% strain amplitude. These data suggest that dynamic loading increases the functionality of our TE-IVDs with region-dependent responses using a method that may be scaled up to larger disc models to expedite maturation for implantation. PMID:25277703

  19. Collagen fibrillogenesis in the development of the annulus fibrosus of the intervertebral disc.

    PubMed

    Hayes, Anthony J; Isaacs, Marc D; Hughes, C; Caterson, B; Ralphs, J R

    2011-10-11

    The annulus fibrosus of the intervertebral disc is a complex, radial-ply connective tissue consisting of concentric lamellae of oriented collagen. Whilst much is known of the structure of the mature annulus, less is known of how its complex collagenous architecture becomes established; an understanding of which could inform future repair/regenerative strategies. Here, using a rat disc developmental series, we describe events in the establishment of the collagenous framework of the annulus at light and electron microscopic levels and examine the involvement of class I and II small leucine rich proteoglycans (SLRPs) in the matrix assembly process. We show that a period of sustained, ordered matrix deposition follows the initial cellular differentiation/orientation phase within the foetal disc. Fibrillar matrix is deposited from recesses within the plasma membrane into compartments of interstitial space within the outer annulus - the orientation of the secreted collagen reflecting the initial cellular orientation of the laminae. Medially, we demonstrate the development of a reinforcing 'cage' of collagen fibre bundles around the foetal nucleus pulpous. This derives from the fusion of collagen bundles between presumptive end-plate and inner annulus. By birth, the distinct collagenous architectures are established and the disc undergoes considerable enlargement to maturity. We show that fibromodulin plays a prominent role in foetal development of the annulus and its attachment to vertebral bodies. With the exception of keratocan, the other SLRPs appear associated more with cartilage development within the vertebral column, but all become more prominent within the disc during its growth and differentiation.

  20. Mechanical Vibrations Reduce the Intervertebral Disc Swelling and Muscle Atrophy from Bed Rest

    NASA Technical Reports Server (NTRS)

    Holguin, Nilsson; Muir, Jesse; Evans, Harlan J.; Qin, Yi-Xian; Rubin, Clinton; Wagshul, Mark; Judex, Stefan

    2007-01-01

    Loss of functional weight bearing, such as experienced during space flight or bed rest (BR), distorts intervertebral disc (IVD) and muscle morphology. IVDs are avascular structures consisting of cells that may derive their nutrition and waste removal from the load induced fluid flow into and out of the disc. A diurnal cycle is produced by forces related to weight bearing and muscular activity, and comprised of a supine and erect posture over a 24 hr period. A diurnal cycle will include a disc volume change of approx. 10-13%. However, in space there are little or no diurnal changes because of the microgravity, which removes the gravitational load and compressive forces to the back muscles. The BR model and the etiology of the disc swelling and muscle atrophy could provide insight into those subjects confined to bed for chronic disease/injury and aging. We hypothesize that extremely low-magnitude, high frequency mechanical vibrations will abate the disc degeneration and muscle loss associated with long-term BR.

  1. The cellular and molecular biology of the intervertebral disc: A clinician’s primer

    PubMed Central

    Erwin, W. Mark; Hood, Katherine E.

    2014-01-01

    Clinicians routinely encounter patients suffering from both degenerative and acute spinal pain, often as a consequence of pathology affecting the intervertebral disc (IVD). The IVD is a complex structure essential to spinal function and is subject to degenerative disease and injury. However, due to the complexity of spinal pain syndromes it is often difficult to determine the extent of the IVD’s contribution to the genesis of spinal pain. The location of the IVD is within close proximity to vital neural elements and may in the event of pathological change or injury compromise those structures. It is therefore important that clinicians performing manual therapy understand the cellular and molecular biology of the IVD as well as its clinical manifestation of degeneration/injury in order to safely manage and appreciate the role played by the disc in the development of mechanical spinal pain syndromes. PMID:25202152

  2. The cellular and molecular biology of the intervertebral disc: A clinician's primer.

    PubMed

    Erwin, W Mark; Hood, Katherine E

    2014-09-01

    Clinicians routinely encounter patients suffering from both degenerative and acute spinal pain, often as a consequence of pathology affecting the intervertebral disc (IVD). The IVD is a complex structure essential to spinal function and is subject to degenerative disease and injury. However, due to the complexity of spinal pain syndromes it is often difficult to determine the extent of the IVD's contribution to the genesis of spinal pain. The location of the IVD is within close proximity to vital neural elements and may in the event of pathological change or injury compromise those structures. It is therefore important that clinicians performing manual therapy understand the cellular and molecular biology of the IVD as well as its clinical manifestation of degeneration/injury in order to safely manage and appreciate the role played by the disc in the development of mechanical spinal pain syndromes.

  3. Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies.

    PubMed

    Wang, S Z; Rui, Y F; Lu, J; Wang, C

    2014-10-01

    Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio-active substances and bio-compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies.

  4. Discoscopic Findings of High Signal Intensity Zones on Magnetic Resonance Imaging of Lumbar Intervertebral Discs

    PubMed Central

    Sugiura, Kosuke; Tonogai, Ichiro; Matsuura, Tetsuya; Higashino, Kosaku; Sakai, Toshinori; Suzue, Naoto; Nishisho, Toshihiko; Goda, Yuichiro; Sato, Ryosuke; Kondo, Kenji; Tezuka, Fumitake; Mineta, Kazuaki; Takeuchi, Makoto; Takahashi, Mitsuhiko; Egawa, Hiroshi; Sairyo, Koichi

    2014-01-01

    A 32-year-old man underwent radiofrequency thermal annuloplasty (TA) with percutaneous endoscopic discectomy (PED) under local anesthesia for chronic low back pain. His diagnosis was discogenic pain with a high signal intensity zone (HIZ) in the posterior corner of the L4-5 disc. Flexion pain was sporadic, and steroid injection was given twice for severe pain. After the third episode of strong pain, PED and TA were conducted. The discoscope was inserted into the posterior annulus and revealed a migrated white nucleus pulposus which was stained blue. Then, after moving the discoscope to the site of the HIZ, a migrated slightly red nucleus pulposus was found, suggesting inflammation and/or new vessels penetrating the mass. After removing the fragment, the HIZ site was ablated by TA. To our knowledge, this is the first report of the discoscopic findings of HIZ of the lumbar intervertebral disc. PMID:24963428

  5. Finite element analysis predicts experimental failure patterns in vertebral bodies loaded via intervertebral discs up to large deformation.

    PubMed

    Clouthier, Allison L; Hosseini, Hadi S; Maquer, Ghislain; Zysset, Philippe K

    2015-06-01

    Vertebral compression fractures are becoming increasingly common. Patient-specific nonlinear finite element (FE) models have shown promise in predicting yield strength and damage pattern but have not been experimentally validated for clinically relevant vertebral fractures, which involve loading through intervertebral discs with varying degrees of degeneration up to large compressive strains. Therefore, stepwise axial compression was applied in vitro on segments and performed in silico on their FE equivalents using a nonlocal damage-plastic model including densification at large compression for bone and a time-independent hyperelastic model for the disc. The ability of the nonlinear FE models to predict the failure pattern in large compression was evaluated for three boundary conditions: healthy and degenerated intervertebral discs and embedded endplates. Bone compaction and fracture patterns were predicted using the local volume change as an indicator and the best correspondence was obtained for the healthy intervertebral discs. These preliminary results show that nonlinear finite element models enable prediction of bone localisation and compaction. To the best of our knowledge, this is the first study to predict the collapse of osteoporotic vertebral bodies up to large compression using realistic loading via the intervertebral discs.

  6. Elevated interleukin-6 expression levels are associated with intervertebral disc degeneration

    PubMed Central

    DENG, XIAO; ZHAO, FENG; KANG, BAOLIN; ZHANG, XIN

    2016-01-01

    The present study aimed to investigate whether serum interleukin-6 (IL-6) expression levels were associated with the onset and progression of intervertebral disc degeneration (IDD). A comprehensive meta-analysis of the scientific literature from numerous electronic databases was performed, in order to obtain published studies associated with the topic of interest. Relevant case-control studies that had previously assessed a correlation between IL-6 expression levels and IDD were identified using predetermined inclusion and exclusion criteria. The STATA version 12.0 software was used for statistical analysis of the extracted data. A total of 112 studies were initially retrieved, with eight studies meeting the inclusion criteria. These contained a total of 392 subjects, of which 263 were patients with IDD and 129 were healthy controls. A meta-analysis of the eight studies demonstrated that serum IL-6 protein expression levels may be associated with IDD, and this was irrespective of IDD subtype (bulging, protrusion, or sequestration). Notably, serum expression levels of the IL-6 protein were upregulated in intervertebral disc (IVD) protrusion tissue, as compared with normal IVD tissue; thus suggesting that IL-6 may have an important role in the pathophysiological process of IDD. PMID:27073460

  7. Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc

    PubMed Central

    Mao, Lu; Han, Xiuguo; Zhang, Kai; Zhao, Changqing

    2016-01-01

    Cordycepin is a component of the extract obtained from Cordyceps militaris and has many biological activities, including anti-cancer, anti-metastatic and anti-inflammatory effects. Intervertebral disc degeneration (IDD) is a degenerative disease that is closely related to the inflammation of nucleus pulposus (NP) cells. The effect of cordycepin on NP cells in relation to inflammation and degeneration has not yet been studied. In our study, we used a rat NP cell culture and an intervertebral disc (IVD) organ culture model to examine the inhibitory effects of cordycepin on lipopolysaccharide (LPS)-induced gene expression and the production of matrix degradation enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and oxidative stress-associated factors (nitric oxide and PGE2). We found a protective effect of cordycepin on NP cells and IVDs against LPS-induced matrix degradation and macrophage infiltration. In addition, western blot and luciferase assay results demonstrated that pretreatment with cordycepin significantly suppressed the LPS-induced activation of the NF-κB pathway. Taken together, the results of our research suggest that cordycepin could exert anti-inflammatory and anti-degenerative effects on NP cells and IVDs by inhibiting the activation of the NF-κB pathway. Therefore, cordycepin may be a potential treatment for IDD in the future. PMID:27190710

  8. Strategies for replicating anatomical cartilaginous tissue gradient in engineered intervertebral disc.

    PubMed

    Bhattacharjee, Maumita; Chameettachal, Shibu; Pahwa, Shikha; Ray, Alok R; Ghosh, Sourabh

    2014-01-08

    A critical challenge in fabricating a load bearing tissue, such as an intervertebral disc, is to simulate cellular and matrix alignment and anisotropy, as well as a specific biochemical gradient. Towards this goal, multilamellar silk fibroin scaffolds having criss-cross fibrous orientation were developed, where silk fibers in inner layers were crosslinked with bioactive molecule chondroitin sulfate. Upon culturing goat articular chondrocytes under static and dynamic conditions, lamellar scaffold architecture guided alignment of cells and the newly synthesized extracellular matrix (ECM) along the silk fibers. The dynamic culture conditions further improved the cellular metabolic rate and ECM production. Further the synergistic effect of chemical composition of scaffold and hydrodynamic environment of bioreactor contributed in developing a tissue gradient within the constructs, with an inner region rich in collagen II, glycosaminoglycan (GAG), and stiffer in compression, whereas an outer region rich in collagen I and stiffer in tension. Therefore, a unique combination of chemical and physical parameters of engineered constructs and dynamic culture conditions provides a promising starting point to further improve the system towards replicating the anatomical structure, composition gradient, and function of intervertebral disc tissue.

  9. Comparison of disability duration of lumbar intervertebral disc disorders among types of insurance in Korea.

    PubMed

    Lee, Choong Ryeol; Kim, Joon Youn; Hong, Young Seoub; Lim, Hyun Sul; Lee, Yong Hwan; Lee, Jong Tae; Moon, Jai Dong; Jeong, Baek Geun

    2005-10-01

    The incidence of work-related musculoskeletal disorder including low back pain sharply increased since 2000 in Korea. The objectives of the present study are to compare disability duration of lumbar intervertebral disc displacement among types of insurances, and to obtain its appropriate duration. The medical records of all patients whose final diagnosis in discharge summary of chart was lumber specified intervertebral disc displacement (LIVD) in 6 large general hospitals in Korea were reviewed to compare the length of admission and disability among different types of insurances. The information on age, gender, the length of admission, the length of follow-up for LIVD, occupation, operation, combined musculoskeletal diseases, and type of insurance was investigated. 552 cases were selected and analyzed to calculate arithmetic mean, median, mode, and geometric mean of disability duration. There was a significant difference in the length of admission and disability among types of insurance after controlling covariates such as age and combined diseases by the analysis of covariance. The length of admission in cases of IACI and AI was much longer than that of HI, and the length of disability in cases of IACI was much longer than that of HI. Prolonged duration of admission and disability was not assumed due to combined diseases, complication or other unexplainable personal factors in cases of those with industrial accidents compensation insurance and automobile insurance. This means that proper management of evidence-based disability duration guidelines is urgently needed in Korea.

  10. Structural and Ultrastructural Analysis of the Cervical Discs of Young and Elderly Humans.

    PubMed

    Fontes, Ricardo Braganca de Vasconcellos; Baptista, Josemberg Silva; Rabbani, Said Rahnamaye; Traynelis, Vincent C; Liberti, Edson Aparecido

    2015-01-01

    Several studies describing the ultrastructure and extracellular matrix (ECM) of intervertebral discs (IVDs) involve animal models and specimens obtained from symptomatic individuals during surgery for degenerative disease or scoliosis, which may not necessarily correlate to changes secondary to normal aging in humans. These changes may also be segment-specific based on different load patterns throughout life. Our objective was to describe the ECM and collagen profile of cervical IVDs in young (G1 - <35 years) and elderly (G2 - >65 years) presumably-asymptomatic individuals. Thirty cervical discs per group were obtained during autopsies of presumably-asymptomatic individuals. IVDs were analyzed with MRI, a morphological grading scale, light microscopy, scanning electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I, II, III, IV, V, VI, IX and X. Macroscopic degenerative features such as loss of annulus-nucleus distinction and fissures were found in both groups and significantly more severe in G2 as expected. MRI could not detect all morphological changes when compared even with simple morphological inspection. The loose fibrocartilaginous G1 matrix was replaced by a denser ECM in G2 with predominantly cartilaginous characteristics, chondrocyte clusters and absent elastic fibers. SEM demonstrated persistence of an identifiable nucleus and Sharpey-type insertion of cervical annulus fibers even in highly-degenerated G2 specimens. All collagen types were detected in every disc sector except for collagen X, with the largest area stained by collagens II and IV. Collagen detection was significantly decreased in G2: although significant intradiscal differences were rare, changes may occur faster or earlier in the posterior annulus. These results demonstrate an extensive modification of the ECM with maintenance of basic ultrastructural features despite severe macroscopic degeneration. Collagen analysis supports there is not a "pathologic" collagen type

  11. The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration

    PubMed Central

    Le Maitre, Christine Lyn; Freemont, Anthony J; Hoyland, Judith Alison

    2005-01-01

    In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1β-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family. This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1β-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration. PMID:15987475

  12. Feasibility of minimally-invasive fiber-based evaluation of chondrodystrophoid canine intervertebral discs by light absorption and scattering spectroscopy

    NASA Astrophysics Data System (ADS)

    Jiang, Yuanyuan; McKeirnan, Kelci; Piao, Daqing; Bartels, Kenneth E.

    2011-03-01

    Extrusion or protrusion of an intervertebral disc is a common, frequently debilitating, painful, and sometimes fatal neurologic disease in the chondrodystrophic dog (dachshund, Pekingese, etc.). A similar condition of intervertebral disc degeneration with extrusion/protrusion is also a relatively common neurologic condition in human patients. Degeneration of the relatively avascular chondrodystrophoid intervertebral disc is associated with loss of water content, increased collagen, and deposits of calcified mineral in the nucleus pulposus. Current diagnostic methods have many limitations for providing accurate information regarding disc composition in situ prior to surgical intervention. Disc composition (i.e., mineralization), can influence the type of treatment regime and potentially prognosis and recurrence rates. The objective of this study is to investigate the feasibility of using a fiber-needle spectroscopy sensor to analyze the changes of tissue compositions involved in the chondrodystrophoid condition of the canine intervertebral disc. The nucleous pulposus, in which the metaplastic process / degeneration develops, is approximately 2mm thick and 5mm in diameter in the dachshund-sized dog. It lies in the center of the disc, surrounded by the annulus fibrosis and is enclosed by cartilaginous vertebral endplates cranially and caudally. This "shallow-and-small-slab" geometry limits the configuration of a fiber probe to sense the disc tissue volume without interference from the vertebrae. A single-fiber sensor is inserted into a 20 gauge myelographic spinal needle for insertion into the disc in situ and connected via a bifurcated fiber to the light source and a spectrometer. A tungsten light source and a 940nm light-emitting-diode are combined for spectral illumination covering VIS/NIR with expected improved sensitivity to water. Analysis of the reflectance spectra is expected to provide information of scattering and absorption compositions of tissue in

  13. Role of biomechanics on intervertebral disc degeneration and regenerative therapies: What needs repairing in the disc and what are promising biomaterials for its repair?

    PubMed Central

    Iatridis, James C.; Nicoll, Steven B.; Michalek, Arthur J.; Walter, Benjamin A.; Gupta, Michelle S.

    2013-01-01

    Background Context Degeneration and injuries of the intervertebral disc result in large alterations in biomechanical behaviors. Repair strategies using biomaterials can be optimized based on biomechanical and biological requirements. Purpose To review current literature on 1) effects of degeneration, simulated degeneration, and injury on biomechanics of the intervertebral disc with special attention paid to needle puncture injuries which are a pathway for diagnostics and regenerative therapies; and 2) promising biomaterials for disc repair with a focus on how those biomaterials may promote biomechanical repair. Study Design/Setting A narrative review to evaluate the role of biomechanics on disc degeneration and regenerative therapies with a focus on what biomechanical properties need to be repaired and how to evaluate and accomplish such repairs using biomaterials. Model systems for screening of such repair strategies are also briefly described. Methods Papers were selected from two main Pubmed searches using keywords: intervertebral AND biomechanics (1823 articles) and intervertebral AND biomaterials (361 articles). Additional keywords (injury, needle puncture, nucleus pressurization, biomaterials, hydrogel, sealant, tissue engineering) were used to narrow articles to the topics most relevant to this review. Results Degeneration and acute disc injuries have the capacity to influence nucleus pulposus pressurization and annulus fibrosus integrity, which are necessary for effective disc function, and therefore, require repair. Needle injection injuries are of particular clinical relevance with potential to influence disc biomechanics, cellularity, and metabolism, yet these effects are localized or small, and more research is required to evaluate and reduce potential clinical morbidity using such techniques. NP replacement strategies, such as hydrogels, are required to restore NP pressurization or lost volume. AF repair strategies, including crosslinked hydrogels

  14. Herb formula "Fufangqishe-Pill" prevents upright posture-induced intervertebral disc degeneration at the lumbar in rats.

    PubMed

    Liang, Qian-Qian; Xi, Zhi-Jie; Bian, Qin; Cui, Xue-Jun; Li, Chen-Guang; Hou, Wei; Shi, Qi; Wang, Yong-Jun

    2010-01-01

    Degeneration of the lumbar spine plays an important role in most chronic low back pain. Prevention of lumbar intervertebral disc (IVD) degeneration is therefore a high research priority. Both our previous multicenter clinical trials and pharmacological research showed that Fufangqishe-Pill (FFQSP), a newly patented traditional Chinese medicine, could effectively relieve the symptoms of neck pain and prevent cervical degeneration. To clarify the effect of FFQSP on lumbar IVD degeneration, we applied a lumbar IVD degeneration rat model induced by prolonged upright posture. Pretreatment of FFQSP for one month prevented the histological changes indicating IVD disorganization; increased type II-collagen level, decreased type X-collagen protein level, and increased Col2alpha1 mRNA expression at all time points; and decreased Col10alpha1, matrix metalloproteinase (MMP)-3, MMP13, and Interleukin (IL)-1beta mRNA expression induced by upright posture for 7 and 9 months. These results suggest that FFQSP prevents lumbar IVD degeneration induced by upright posture. FFQSP is a promising medicine for lumbar IVD degeneration disease.

  15. MSC response to pH levels found in degenerating intervertebral discs

    SciTech Connect

    Wuertz, Karin Godburn, Karolyn; Iatridis, James C.

    2009-02-20

    Painful degenerative disc disease is a major health problem and for successful tissue regeneration, MSCs must endure and thrive in a harsh disc microenvironment that includes matrix acidity as a critical factor. MSCs were isolated from bone marrow of Sprague-Dawley rats from two different age groups (<1 month, n = 6 and 4-5 months, n = 6) and cultured under four different pH conditions representative of the healthy, mildly or severely degenerated intervertebral disc (pH 7.4, 7.1, 6.8, and 6.5) for 5 days. Acidity caused an inhibition of aggrecan, collagen-1, and TIMP-3 expression, as well as a decrease in proliferation and viability and was associated with a change in cell morphology. Ageing had generally minor effects but young MSCs maintained greater mRNA expression levels. As acidic pH levels are typical of increasingly degenerated discs, our findings demonstrate the importance of early interventions and predifferentiation when planning to use MSCs for reparative treatments.

  16. The Effects of Platelet-Rich Plasma on Halting the Progression in Porcine Intervertebral Disc Degeneration.

    PubMed

    Cho, Hongsik; Holt, David C; Smith, Richard; Kim, Song-Ja; Gardocki, Raymond J; Hasty, Karen A

    2016-02-01

    Disc degeneration and the subsequent herniation and/or rupture of the intervertebral disc (IVD) are due to a failure of the extracellular matrix of the annulus to contain the contents of the nucleus. This results from inadequate maintenance of the matrix components as well as the proteolytic activity of matrix metalloproteinases (MMPs) that degrade matrix molecules. Arresting progression of disc degeneration in the annulus holds greater clinical potential at this point than prevention of its onset in the nucleus. Therefore, in this study, we have therapeutic aims that would decrease levels of the cytokines and growth factors that indirectly lead to disc degeneration via stimulating MMP and increase levels of several beneficial growth factors, such as transforming growth factor-β, with the addition of platelet-rich plasma (PRP) that would stimulate cell growth and matrix synthesis. For this study, we attempted to address these imbalances of metabolism by using tumor necrosis factor-α treated annulus fibrosus cells isolated from porcine IVD tissue and incubating the cells in a growth factor rich environment with PRP. These results indicate that the PRP in vitro increased the production of the major matrix components (type II collagen and aggrecan) and decreased the inhibitory collagenase MMP-1. This application will address a therapeutic approach for intervening early in the degenerative process.

  17. An In Vivo Model of Reduced Nucleus Pulposus Glycosaminoglycan Content in the Rat Lumbar Intervertebral Disc

    PubMed Central

    Boxberger, John I.; Auerbach, Joshua D.; Sen, Sounok; Elliott, Dawn M.

    2009-01-01

    Study Design An in vivo model resembling early stage disc degeneration in the rat lumbar spine. Objective Simulate the reduced glycosaminoglycan content and altered mechanics observed in intervertebral disc degeneration using a controlled injection of chondroitinase ABC (ChABC). Summary of Background Data Nucleus glycosaminoglycan reduction occurs early during disc degeneration; however, mechanisms through which degeneration progresses from this state are unknown. Animal models simulating this condition are essential for understanding disease progression and for development of therapies aimed at early intervention. Methods ChABC was injected into the nucleus pulposus, and discs were evaluated via micro-CT, mechanical testing, biochemical assays, and histology 4 and 12 weeks after injection. Results At 4 weeks, reductions in nucleus glycosaminoglycan level by 43%, average height by 12%, neutral zone modulus by 40%, and increases in range of motion by 40%, and creep strain by 25% were found. Neutral zone modulus and range of motion were correlated with nucleus glycosaminoglycan. At 12 weeks, recovery of some mechanical function was detected as range of motion and creep returned to control levels; however, this was not attributed to glycosaminoglycan restoration, because mechanics were no longer correlated with glycosaminoglycan. Conclusion An in vivo model simulating physiologic levels of glycosaminoglycan loss was created to aid in understanding the relationships between altered biochemistry, altered mechanics, and altered cellular function in degeneration. PMID:18197098

  18. Spinal Epidural Varices, a great Mimic of Intervertebral Disc Prolapse - A Case Series

    PubMed Central

    V, Raghavendra; Haridas, Papanaik; Kumar, Anand; K, Ajith

    2014-01-01

    Introduction: Epidural venous plexus enlargement, presenting with low back pain and radiculopathy, is an uncommon cause of nerve roots impingement. This condition commonly mimics a herniated nucleus pulposus radiologically. The radiological diagnosis is often missed and the diagnosis is made during the surgery. We are hereby presenting 2 such cases of epidural varices mimicking intervertebral disc prolapse with lumbar radiculopathy. Case Report: Case 1: 43 yr old female presented with acute exacerbation of low back ache and significant right L5–S1 radiculopathy without neurological deficit. MRI reported as L5-S1 disc prolapse. Intra-operatively engorged dilated epidural vein seen compressing S1 nerve root. Associated Disc bulge removed and Coagulative ablation of the dilated epidural vein was performed Case 2: 45 year old male manual labourer presented with backache with left sided sciatica since 8 months, increased in severity since past 1month associated with sensory blunting in L5 and S1 dermatomes. Neurologic examination revealed normal muscle power in his lower extremities. Sensations was blunted in L5 and S1 dermatomes. MRI was reported as L5-S1 disc prolapsed compressing left S1 nerve root. Decompression of the L5–S1 intervertebral space was performed through a left –sidelaminotomy. Large, engorged serpentine epidural veins was found in the axilla of S1 nerve root, compressing it. Coagulative ablation of the dilated epidural vein was performed. Retrospectively, features of epidural varices were noted in the preoperative magnetic resonance imaging scans. Both patients had significant improvement in radiculopathy immediate postoperatively, and sensory symptoms resolved over the next 6 weeks in second case. At recent follow up, both patients had significant relief of symptoms and no recurrent radicular symptoms. Conclusion: An abnormal dilated epidural venous plexus that mimics a herniated lumbar disc is a rare entity. This pathology should be always kept

  19. Traumatic Migration of the Bryan Cervical Disc Arthroplasty.

    PubMed

    Wagner, Scott C; Kang, Daniel G; Helgeson, Melvin D

    2016-02-01

    Study Design Case study. Objective To describe a case of dislodgment and migration of the Bryan Cervical Disc (Medtronic Sofamor Danek, Memphis, Tennessee, United States) arthroplasty more than 6 months after implantation secondary to low-energy trauma. Methods The inpatient, outpatient, and radiographic medical records of a patient with traumatic migration of the Bryan Cervical Disc arthroplasty were reviewed. The authors have no relevant disclosures to report. Results A 36-year-old man with chronic left upper extremity radiculopathy underwent uncomplicated Bryan Cervical Disc arthroplasty at C5-C6, with complete resolution of his symptoms. Approximately 6 months after his index procedure, he sustained low-energy trauma to the posterior cervical spine, after being struck by a book falling from a shelf. The injury forced his neck into flexion, and though he did not have recurrence of his radiculopathy symptoms, radiographs demonstrated anterior migration of the arthroplasty device. He underwent revision to anterior cervical diskectomy and fusion. Conclusions Although extremely rare, it is imperative that surgeons consider the potential for failure of osseous integration in patients undergoing cervical disk arthroplasty, even beyond 3 to 6 months postoperatively. This concern is especially relevant to press-fit or milled devices like the Bryan Cervical Disc arthroplasty, which lack direct fixation into adjacent vertebral bodies. We are considering modification of our postoperative protocol to improve protection of the device after implantation, even beyond 3 months postoperatively.

  20. Traumatic Migration of the Bryan Cervical Disc Arthroplasty

    PubMed Central

    Wagner, Scott C.; Kang, Daniel G.; Helgeson, Melvin D.

    2015-01-01

    Study Design Case study. Objective To describe a case of dislodgment and migration of the Bryan Cervical Disc (Medtronic Sofamor Danek, Memphis, Tennessee, United States) arthroplasty more than 6 months after implantation secondary to low-energy trauma. Methods The inpatient, outpatient, and radiographic medical records of a patient with traumatic migration of the Bryan Cervical Disc arthroplasty were reviewed. The authors have no relevant disclosures to report. Results A 36-year-old man with chronic left upper extremity radiculopathy underwent uncomplicated Bryan Cervical Disc arthroplasty at C5–C6, with complete resolution of his symptoms. Approximately 6 months after his index procedure, he sustained low-energy trauma to the posterior cervical spine, after being struck by a book falling from a shelf. The injury forced his neck into flexion, and though he did not have recurrence of his radiculopathy symptoms, radiographs demonstrated anterior migration of the arthroplasty device. He underwent revision to anterior cervical diskectomy and fusion. Conclusions Although extremely rare, it is imperative that surgeons consider the potential for failure of osseous integration in patients undergoing cervical disk arthroplasty, even beyond 3 to 6 months postoperatively. This concern is especially relevant to press-fit or milled devices like the Bryan Cervical Disc arthroplasty, which lack direct fixation into adjacent vertebral bodies. We are considering modification of our postoperative protocol to improve protection of the device after implantation, even beyond 3 months postoperatively. PMID:26835211

  1. Stress - Strain Response of the Human Spine Intervertebral Disc As an Anisotropic Body. Mathematical Modeling and Computation

    NASA Astrophysics Data System (ADS)

    Minárová, Mária; Sumec, Jozef

    2016-01-01

    The paper deals with the biomechanical investigation on the human lumbar intervertebral disc under the static load. The disc is regarded as a two - phased ambient consisting of a fibrous outer part called annulus fibrosis and a liquid inner part nucleus pulposus. Due to the fibrous structure, the annulus fibrosis can be treated by using a special case of anisotropy - transversal isotropy. In the paper the corresponding tensor of material constants is derived. The tensor consequently incomes to the constitutive equations determining the stress - strain relation in the material. In order to study the mechanical behaviour the disc is observed within the motion segment, the basic unit for motion tracing. The motion segment involves two neighbouring vertebrae and the intervertebral disc between them that connect them both. When constitutive equations are accomplished, they can be incorporated in the finite element analysis. The illustrative example of the intervertebral disc L2/L3, the disc between the second and the third lumbar vertebrae the lumbar part of spine, with its computer implementation is performed. Finally the comparison of the results of using anisotropic and homogenized approach is provided. The comparison illustrates the eligibility of such a kind of approach.

  2. Adipose-Derived Stromal Cells Protect Intervertebral Disc Cells in Compression: Implications for Stem Cell Regenerative Disc Therapy

    PubMed Central

    Sun, Zhen; Luo, Beier; Liu, Zhi-Heng; Samartzis, Dino; Liu, Zhongyang; Gao, Bo; Huang, Liangliang; Luo, Zhuo-Jing

    2015-01-01

    Introduction: Abnormal biomechanics plays a role in intervertebral disc degeneration. Adipose-derived stromal cells (ADSCs) have been implicated in disc integrity; however, their role in the setting of mechanical stimuli upon the disc's nucleus pulposus (NP) remains unknown. As such, the present study aimed to evaluate the influence of ADSCs upon NP cells in compressive load culture. Methods: Human NP cells were cultured in compressive load at 3.0MPa for 48 hours with or without ADSCs co-culture (the ratio was 50:50). We used flow cytometry, live/dead staining and scanning electron microscopy (SEM) to evaluate cell death, and determined the expression of specific apoptotic pathways by characterizing the expression of activated caspases-3, -8 and -9. We further used real-time (RT-) PCR and immunostaining to determine the expression of the extracellular matrix (ECM), mediators of matrix degradation (e.g. MMPs, TIMPs and ADAMTSs), pro-inflammatory factors and NP cell phenotype markers. Results: ADSCs inhibited human NP cell apoptosis via suppression of activated caspase-9 and caspase-3. Furthermore, ADSCs protected NP cells from the degradative effects of compressive load by significantly up-regulating the expression of ECM genes (SOX9, COL2A1 and ACAN), tissue inhibitors of metalloproteinases (TIMPs) genes (TIMP-1 and TIMP-2) and cytokeratin 8 (CK8) protein expression. Alternatively, ADSCs showed protective effect by inhibiting compressive load mediated increase of matrix metalloproteinases (MMPs; MMP-3 and MMP-13), disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs; ADAMTS-1 and 5), and pro-inflammatory factors (IL-1beta, IL-6, TGF-beta1 and TNF-alpha). Conclusions: Our study is the first in vitro study assessing the impact of ADSCs on NP cells in an un-physiological mechanical stimulation culture environment. Our study noted that ADSCs protect compressive load induced NP cell death and degradation by inhibition of activated caspase-9 and -3

  3. Outcomes following cervical disc arthroplasty: a retrospective review.

    PubMed

    Cody, John P; Kang, Daniel G; Tracey, Robert W; Wagner, Scott C; Rosner, Michael K; Lehman, Ronald A

    2014-11-01

    Cervical disc arthroplasty has emerged as a viable technique for the treatment of cervical radiculopathy and myelopathy, with the proposed benefit of maintenance of segmental range of motion. There are relatively few, non-industry sponsored studies examining the outcomes and complications of cervical disc arthroplasty. Therefore, we set out to perform a single center evaluation of the outcomes and complications of cervical disc arthroplasty. We performed a retrospective review of all patients from a single military tertiary medical center undergoing cervical disc arthroplasty from August 2008 to August 2012. The clinical outcomes and complications associated with the procedure were evaluated. A total of 219 consecutive patients were included in the review, with an average follow-up of 11.2 (±11.0)months. Relief of pre-operative symptoms was noted in 88.7% of patients, and 92.2% of patients were able to return to full pre-operative activity. There was a low rate of complications related to the anterior cervical approach (3.2% with recurrent laryngeal nerve injury, 8.9% with dysphagia), with no device/implant related complications. Symptomatic cervical radiculopathy is a common problem in both the civilian and active duty military populations and can cause significant disability leading to loss of work and decreased operational readiness. There exist several surgical treatment options for appropriately indicated patients. Based on our findings, cervical disc arthroplasty is a safe and effective treatment for symptomatic cervical radiculopathy and myelopathy, with a low incidence of complications and high rate of symptom relief.

  4. [Correlation between shape and direction of small articular surface in lower lumbar vertebrae and degeneration of intervertebral disc].

    PubMed

    Tan, L; Bai, X; Li, D

    1997-01-01

    To assess the possible correlation between the shape and the direction of the small articular surface in the lower lumbar vertebrae and the degeneration of the intervertebral disc, we investigated with computed tomography (CT) and evaluated with statistics the small articular surface and the transverse interface-joint angle (TIFA) of the L4-5 and the L5-S1 in 152 cases who had normal or degenerative discs verified through CT, MRI or operation. The small articular surface was found arc in 69.1% of the L4-5 and in 23.0% of the L5-S1. The TIFA of the L4-5 was less than that of the L5-S1. There was no correlation between the ratio of degeneration of the intervertebral disc at the L4-5 and the TIFA of the L4-5 and the L5-S1, but the ratio of degeneration of the intervertebral disc at the L5-S1 had postive correlation with the TIFA of the L4-5, negative correlation with the TIFA of the L5-S1, and particular correlation with the TIFA of the L5-S1 and L4-5. These results suggest that the shape and direction of the lower lumbar facet joint are related to the lumbar degeneration of intervertebral disc and the causes of degeneration at the L4-5 disc differ from those at the L5-S1 disc in biomechanics.

  5. A novel approach for the annulus needle puncture model of intervertebral disc degeneration in rabbits

    PubMed Central

    Lei, Tao; Zhang, Yuan; Zhou, Qiang; Luo, Xiaoji; Tang, Ke; Chen, Rongsheng; Yu, Chang; Quan, Zhengxue

    2017-01-01

    Objective: To create the rabbit animal model of intervertebral disc (IVD) degeneration by the annulus needle puncture technique through a novel transabdominal approach. Methods: Thirteen New Zealand White rabbits underwent annular puncture at the L3/4, L4/5, and L5/6 discs through a transabdominal approach. For a longitudinal study to assess changes in disc height over time, serial X-rays, T2-weighted magnetic resonance imaging (MRI) (T2WI), and T2 mapping MRI were performed pre-operation and at 2, 4, and 6 weeks after puncture. Three rabbits were randomly selected for histological evaluation at 4 weeks post-operation. In addition, the remaining rabbits underwent a second surgery at 6 weeks after puncture. Results: All rabbits underwent the initial and second surgeries successfully without nerve-related complications. The operations had no significant effects on the rabbit body weight, and partial mild intra-abdominal adhesions were found in only 1 rabbit. The punctured discs were confirmed to be those of interest post-surgery and displayed progressive degeneration in disc height index (%), T2WI, and T2 relaxation time over time. At 4 weeks after puncture, a histological analysis revealed notochordal cell loss from the nucleus pulposus, fibrocartilage filling the nucleus pulposus space, and annulus fibrosus disorganization. Conclusion: The annular needle puncture model established through a transabdominal approach, which demonstrates better visualization, exact identification, consistent degeneration degrees and minimal complications, is radiologically and histologically consistent with human IVD degeneration. T2 mapping MRI can quantitatively discriminate between grades of mild degeneration. PMID:28386320

  6. Spatial and structural dependence of mechanical properties of porcine intervertebral disc.

    PubMed

    Causa, F; Manto, L; Borzacchiello, A; De Santis, R; Netti, P A; Ambrosio, L; Nicolais, L

    2002-12-01

    Structure-function relationship of natural tissues is crucial to design a device mimicking the structures present in human body. For this purpose, to provide guidelines to design an intervertebral disc (IVD) substitute, in this study the influence of the spatial location and structural components on the mechanical properties of porcine IVD was investigated. Local compressive stiffness (LCS) was measured on the overall disc, also constrained between the two adjacent vertebrae: the dependence on the lumbar position was evaluated. The compliance values in the anterior position (A) were higher than both in the central posterior (CP) and in the lateral-posterior (RP, LP) locations. The values of Young's Modulus (74.67+/-6.03 MPa) and compression break load (1.36x10(4)+/-0.09x10(4)N) of the disc were also evaluated by distributed compression test. The NP rheological behavior was typical of weak-gels, with elastic modulus G' always higher than viscous modulus G" all over the frequency range investigated (G' and G" respectively equal to 320 and 85 Pa at 1 Hz) and with the moduli trends were almost parallel to each other.

  7. Genipin-crosslinked fibrin hydrogels as a potential adhesive to augment intervertebral disc annulus repair.

    PubMed

    Schek, R M; Michalek, A J; Iatridis, J C

    2011-04-18

    Treatment of damaged intervertebral discs is a significant clinical problem and, despite advances in the repair and replacement of the nucleus pulposus, there are few effective strategies to restore defects in the annulus fibrosus. An annular repair material should meet three specifications: have a modulus similar to the native annulus tissue, support the growth of disc cells, and maintain adhesion to tissue under physiological strain levels. We hypothesized that a genipin crosslinked fibrin gel could meet these requirements. Our mechanical results showed that genipin crosslinked fibrin gels could be created with a modulus in the range of native annular tissue. We also demonstrated that this material is compatible with the in vitro growth of human disc cells, when genipin:fibrin ratios were 0.25:1 or less, although cell proliferation was slower and cell morphology more rounded than for fibrin alone. Finally, lap tests were performed to evaluate adhesion between fibrin gels and pieces of annular tissue. Specimens created without genipin had poor handling properties and readily delaminated, while genipin crosslinked fibrin gels remained adhered to the tissue pieces at strains exceeding physiological levels and failed at 15-30%. This study demonstrated that genipin crosslinked fibrin gels show promise as a gap-filling adhesive biomaterial with tunable material properties, yet the slow cell proliferation suggests this biomaterial may be best suited as a sealant for small annulus fibrosus defects or as an adhesive to augment large annulus repairs. Future studies will evaluate degradation rate, fatigue behaviors, and long-term biocompatibility.

  8. Intervertebral disc responses during spinal loading with MRI-compatible spinal compression apparatus

    NASA Astrophysics Data System (ADS)

    Mitsui, Iwane; Yamada, Yoshiya

    2004-07-01

    This study addresses the development of an MRI-compatible spinal compression harness for use as a research and diagnostic tool. This apparatus adds valuable information to MRI imaging regarding the physiology/biomechanics of intervertebral discs and pathophysiology of back pain in patients and astronauts in space. All materials of the spinal compression apparatus are non-metallic for MRI compatibility. The compact design fits into standard MRI or CT scanners and loading is adjusted to specific percentages of BW with elastic cords. Previously this capability has not been available. Three healthy male subjects were fitted with a spinal compression harness and placed supine in a MRI scanner. Longitudinal distance between T7/8 and L5/S1 discs decreased 5.6 mm with 50% BW compression. Lumbosacral angle increased 17.2 degrees. T2 values of nucleus pulposus from L1/2 to L5/S1 discs increased 18.2+/-6.1% (+/-SD) during 50% BW compression and 25.3+/-7.4% (+/-SD) during 75% BW compression.

  9. Intervertebral disc biomechanical analysis using the finite element modeling based on medical images.

    PubMed

    Li, Haiyun; Wang, Zheng

    2006-01-01

    In this paper, a 3D geometric model of the intervertebral and lumbar disks has been presented, which integrated the spine CT and MRI data-based anatomical structure. Based on the geometric model, a 3D finite element model of an L1-L2 segment was created. Loads, which simulate the pressure from above were applied to the FEM, while a boundary condition describing the relative L1-L2 displacement is imposed on the FEM to account for 3D physiological states. The simulation calculation illustrates the stress and strain distribution and deformation of the spine. The method has two characteristics compared to previous studies: first, the finite element model of the lumbar are based on the data directly derived from medical images such as CTs and MRIs. Second, the result of analysis will be more accurate than using the data of geometric parameters. The FEM provides a promising tool in clinical diagnosis and for optimizing individual therapy in the intervertebral disc herniation.

  10. lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis.

    PubMed

    Chen, Wen-Kang; Yu, Xiao-Hua; Yang, Wei; Wang, Cheng; He, Wen-Si; Yan, Yi-Guo; Zhang, Jian; Wang, Wen-Jun

    2017-02-01

    The term long non-coding RNA (lncRNA) refers to a group of RNAs with length more than 200 nucleotides, limited protein-coding potential, and having widespread biological functions, including regulation of transcriptional patterns and protein activity, formation of endogenous small interfering RNAs (siRNAs) and natural microRNA (miRNA) sponges. Intervertebral disc degeneration (IDD) and osteoarthritis (OA) are the most common chronic, prevalent and age-related degenerative musculoskeletal disorders. Numbers of lncRNAs are differentially expressed in human degenerative nucleus pulposus tissue and OA cartilage. Moreover, some lncRNAs have been shown to be involved in multiple pathological processes during OA, including extracellular matrix (ECM) degradation, inflammatory responses, apoptosis and angiogenesis. In this review, we summarize current knowledge concerning lncRNAs, from their biogenesis, classification and biological functions to molecular mechanisms and therapeutic potential in IDD and OA.

  11. Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs

    PubMed Central

    Nakamichi, Ryo; Ito, Yoshiaki; Inui, Masafumi; Onizuka, Naoko; Kayama, Tomohiro; Kataoka, Kensuke; Suzuki, Hidetsugu; Mori, Masaki; Inagawa, Masayo; Ichinose, Shizuko; Lotz, Martin K.; Sakai, Daisuke; Masuda, Koichi; Ozaki, Toshifumi; Asahara, Hiroshi

    2016-01-01

    The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx−/− mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration. PMID:27527664

  12. New approaches to magnetic resonance imaging of intervertebral discs, tendons, ligaments, and menisci.

    PubMed

    Bydder, Graeme M

    2002-06-15

    This review article discusses new magnetic resonance techniques for imaging collagen containing structures such as intervertebral discs, tendons, and ligaments. The semisolid collagen in tendons and ligaments is not normally demonstrable with magnetic resonance imaging but may be visualized with magic angle imaging and other techniques. This allows these structures to be studied with methods used for other tissues and organs. The ordered nature of collagen provides a directional signature for the tissues that may be of diagnostic value. Solute transport in these avascular or partially avascular structures can be observed with gadolinium chelates. The time scale of this process is much slower than for other tissues of the body. Solid state imaging techniques applied in applied in material sciences may provide other new approaches to diagnosis of disease in these structures.

  13. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation.

    PubMed

    Vadalà, Gianluca; Sowa, Gwendolyn; Hubert, Mark; Gilbertson, Lars G; Denaro, Vincenzo; Kang, James D

    2012-05-01

    Recent studies have shown that mesenchymal stem cell (MSC)-based therapy might be an effective approach for the treatment of intervertebral disc degeneration (IDD). However, many unanswered questions remain before clinical translation, such as the most effective stem cell type, a reliable transplantation method, including the carrier choice, and the fate of stem cells after misdirected delivery, among others. The objective of the study was to evaluate the fate and effect of allogenic bone marrow MSCs after transplantation into an IDD model. The L2-3, L3-4 and L4-5 intervertebral discs (IVDs) of four rabbits were stabbed to create IDD. Rabbit MSCs were expanded in vitro and in part transduced with retrovirus/eGFP. After 3 weeks, 1 × 10(5) MSCs were injected into the IVDs. The rabbits were followed by X-ray and MRI 3 and 9 weeks after injection. Then the animals were sacrificed and the spines analysed histologically. MRI showed no signs of regeneration. X-ray and gross anatomy inspection demonstrated large anterolateral osteophytes. Histological analysis showed that the osteophytes were composed of mineralized tissue surrounded by chondrocytes, with the labelled MSCs among the osteophyte-forming cells. The labelled MSCs were not found in the nucleus. Inflammatory cells were not observed in any injected IVDs. These results raise concern that MSCs can migrate out of the nucleus and undesirable bone formation may occur. While cause cannot be inferred from this study, the presence of MSCs in the osteophytes suggests a potential side-effect with this approach. IVD regeneration strategies need to focus on cell carrier systems and annulus-sealing technologies to avoid pitfalls.

  14. Three-dimensional intervertebral range of motion in the cervical spine: Does the method of calculation matter?

    PubMed

    Anderst, William J; Aucie, Yashar

    2017-03-01

    Intervertebral range of motion (ROM) is commonly calculated using ordered rotations or projection angles. Ordered rotations are sequence-dependent, and projection angles are dependent upon on which orientation vectors are projected. This study assessed the effect of calculation method on intervertebral ROM in the subaxial cervical spine (C3-C7) during in vivo dynamic, three-dimensional, functional movement. Biplane radiographs were collected at 30 images per second while 29 participants performed full ROM flexion/extension, axial rotation and lateral bending movements of their cervical spine. In vivo bone motion was tracked with sub-millimeter accuracy using a validated volumetric model-based tracking technique. Intervertebral rotations were calculated using six Cardan angle sequences and two projection angle combinations. Within-subject comparisons revealed significant differences in intervertebral ROM among calculation methods (all p<0.002). Group mean ROM differences were small, but significantly different among calculation methods (p<0.001). A resampling technique demonstrated that as group size increases, the differences between calculation methods decreases substantially. It is concluded that the method used to calculate intervertebral rotations of the sub-axial cervical spine can significantly affect within-subject and between group comparisons of intervertebral ROM.

  15. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

    PubMed

    Hirata, Hiroaki; Yurube, Takashi; Kakutani, Kenichiro; Maeno, Koichiro; Takada, Toru; Yamamoto, Junya; Kurakawa, Takuto; Akisue, Toshihiro; Kuroda, Ryosuke; Kurosaka, Masahiro; Nishida, Kotaro

    2014-03-01

    The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.

  16. A meta-model analysis of a finite element simulation for defining poroelastic properties of intervertebral discs.

    PubMed

    Nikkhoo, Mohammad; Hsu, Yu-Chun; Haghpanahi, Mohammad; Parnianpour, Mohamad; Wang, Jaw-Lin

    2013-06-01

    Finite element analysis is an effective tool to evaluate the material properties of living tissue. For an interactive optimization procedure, the finite element analysis usually needs many simulations to reach a reasonable solution. The meta-model analysis of finite element simulation can be used to reduce the computation of a structure with complex geometry or a material with composite constitutive equations. The intervertebral disc is a complex, heterogeneous, and hydrated porous structure. A poroelastic finite element model can be used to observe the fluid transferring, pressure deviation, and other properties within the disc. Defining reasonable poroelastic material properties of the anulus fibrosus and nucleus pulposus is critical for the quality of the simulation. We developed a material property updating protocol, which is basically a fitting algorithm consisted of finite element simulations and a quadratic response surface regression. This protocol was used to find the material properties, such as the hydraulic permeability, elastic modulus, and Poisson's ratio, of intact and degenerated porcine discs. The results showed that the in vitro disc experimental deformations were well fitted with limited finite element simulations and a quadratic response surface regression. The comparison of material properties of intact and degenerated discs showed that the hydraulic permeability significantly decreased but Poisson's ratio significantly increased for the degenerated discs. This study shows that the developed protocol is efficient and effective in defining material properties of a complex structure such as the intervertebral disc.

  17. Cervical Deuk Laser Disc Repair®: A novel, full-endoscopic surgical technique for the treatment of symptomatic cervical disc disease

    PubMed Central

    Deukmedjian, Ara J.; Cianciabella, Augusto; Cutright, Jason; Deukmedjian, Arias

    2012-01-01

    Background: Cervical Deuk Laser Disc Repair® is a novel full-endoscopic, anterior cervical, trans-discal, motion preserving, laser assisted, nonfusion, outpatient surgical procedure to safely treat symptomatic cervical disc diseases including herniation, spondylosis, stenosis, and annular tears. Here we describe a new endoscopic approach to cervical disc disease that allows direct visualization of the posterior longitudinal ligament, posterior vertebral endplates, annulus, neuroforamina, and herniated disc fragments. All patients treated with Deuk Laser Disc Repair were also candidates for anterior cervical discectomy and fusion (ACDF). Methods: A total of 142 consecutive adult patients with symptomatic cervical disc disease underwent Deuk Laser Disc Repair during a 4-year period. This novel procedure incorporates a full-endoscopic selective partial decompressive discectomy, foraminoplasty, and posterior annular debridement. Postoperative complications and average volume of herniated disc fragments removed are reported. Results: All patients were successfully treated with cervical Deuk Laser Disc Repair. There were no postoperative complications. Average volume of herniated disc material removed was 0.09 ml. Conclusions: Potential benefits of Deuk Laser Disc Repair for symptomatic cervical disc disease include lower cost, smaller incision, nonfusion, preservation of segmental motion, outpatient, faster recovery, less postoperative analgesic use, fewer complications, no hardware failure, no pseudoarthrosis, no postoperative dysphagia, and no increased risk of adjacent segment disease as seen with fusion. PMID:23230523

  18. Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration.

    PubMed

    Nasto, Luigi A; Robinson, Andria R; Ngo, Kevin; Clauson, Cheryl L; Dong, Qing; St Croix, Claudette; Sowa, Gwendolyn; Pola, Enrico; Robbins, Paul D; Kang, James; Niedernhofer, Laura J; Wipf, Peter; Vo, Nam V

    2013-07-01

    Oxidative damage is a well-established driver of aging. Evidence of oxidative stress exists in aged and degenerated discs, but it is unclear how it affects disc metabolism. In this study, we first determined whether oxidative stress negatively impacts disc matrix metabolism using disc organotypic and cell cultures. Mouse disc organotypic culture grown at atmospheric oxygen (20% O(2)) exhibited perturbed disc matrix homeostasis, including reduced proteoglycan synthesis and enhanced expression of matrix metalloproteinases, compared to discs grown at low oxygen levels (5% O(2)). Human disc cells grown at 20% O(2) showed increased levels of mitochondrial-derived superoxide anions and perturbed matrix homeostasis. Treatment of disc cells with the mitochondria-targeted reactive oxygen species (ROS) scavenger XJB-5-131 blunted the adverse effects caused by 20% O(2). Importantly, we demonstrated that treatment of accelerated aging Ercc1(-/Δ) mice, previously established to be a useful in vivo model to study age-related intervertebral disc degeneration (IDD), also resulted in improved disc total glycosaminoglycan content and proteoglycan synthesis. This demonstrates that mitochondrial-derived ROS contributes to age-associated IDD in Ercc1(-/Δ) mice. Collectively, these data provide strong experimental evidence that mitochondrial-derived ROS play a causal role in driving changes linked to aging-related IDD and a potentially important role for radical scavengers in preventing IDD.

  19. Targeting the extracellular matrix: matricellular proteins regulate cell-extracellular matrix communication within distinct niches of the intervertebral disc.

    PubMed

    Bedore, Jake; Leask, Andrew; Séguin, Cheryle A

    2014-07-01

    The so-called "matricellular" proteins have recently emerged as important regulators of cell-extracellular matrix (ECM) interactions. These proteins modulate a variety of cell functions through a range of interactions with cell-surface receptors, hormones, proteases and structural components of the ECM. As such, matricellular proteins are crucial regulators of cell phenotype, and consequently tissue function. The distinct cell types and microenvironments that together form the IVD provide an excellent paradigm to study how matricellular proteins mediate communication within and between adjacent tissue types. In recent years, the role of several matricellular proteins in the intervertebral disc has been explored in vivo using mutant mouse models in which the expression of target matricellular proteins was deleted from either one or all compartments of the intervertebral disc. The current review outlines what is presently known about the roles of the matricellular proteins belonging to the CCN family, SPARC (Secreted Protein, Acidic, and Rich in Cysteine), and thrombospondin (TSP) 2 in regulating intervertebral disc cell-ECM interactions, ECM synthesis and disc tissue homeostasis using genetically modified mouse models. Furthermore, we provide a brief overview of recent preliminary studies of other matricellular proteins including, periostin (POSTN) and tenascin (TN). Each specific tissue type of the IVD contains a different matricellular protein signature, which varies based on the specific stage of development, maturity or disease. A growing body of direct genetic evidence links IVD development, maintenance and repair to the coordinate interaction of matricellular proteins within their respective niches and suggests that several of these signaling modulators hold promise in the development of diagnostics and/or therapeutics targeting intervertebral disc aging and/or degeneration.

  20. Unique glycosignature for intervertebral disc and articular cartilage cells and tissues in immaturity and maturity

    PubMed Central

    Collin, E. C.; Kilcoyne, M.; White, S. J.; Grad, S.; Alini, M.; Joshi, L.; Pandit, A. S.

    2016-01-01

    In this study, on/off markers for intervertebral disc (IVD) and articular cartilage (AC) cells (chondrocytes) and distinct glycoprofiles of cell and tissue-types were identified from immaturity to maturity. Three and eleven month-old ovine IVD and AC tissues were histochemically profiled with a panel of lectins and antibodies. Relationships between tissue and cell types were analysed by hierarchical clustering. Chondroitin sulfate (CS) composition of annulus fibrosus (AF), nucleus pulposus (NP) and AC tissues was determined by HPLC analysis. Clear on/off cell type markers were identified, which enabled the discrimination of chondrocytes, AF and NP cells. AF and NP cells were distinguishable using MAA, SNA-I, SBA and WFA lectins, which bound to both NP cells and chondrocytes but not AF cells. Chondrocytes were distinguished from NP and AF cells with a specific binding of LTA and PNA lectins to chondrocytes. Each tissue showed a unique CS composition with a distinct switch in sulfation pattern in AF and NP tissues upon disc maturity while cartilage maintained the same sulfation pattern over time. In conclusion, distinct glycoprofiles for cell and tissue-types across age groups were identified in addition to altered CS composition and sulfation patterns for tissue types upon maturity. PMID:26965377

  1. T1ρ magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging

    PubMed Central

    Zhang, Qinwei; Li, Xiaojuan; Chen, Weitian; Ahuja, Anil; Yuan, Jing

    2015-01-01

    T1ρ relaxation time provides a new contrast mechanism that differs from T1- and T2-weighted contrast, and is useful to study low-frequency motional processes and chemical exchange in biological tissues. T1ρ imaging can be performed in the forms of T1ρ-weighted image, T1ρ mapping and T1ρ dispersion. T1ρ imaging, particularly at low spin-lock frequency, is sensitive to B0 and B1 inhomogeneity. Various composite spin-lock pulses have been proposed to alleviate the influence of field inhomogeneity so as to reduce the banding-like spin-lock artifacts. T1ρ imaging could be specific absorption rate (SAR) intensive and time consuming. Efforts to address these issues and speed-up data acquisition are being explored to facilitate wider clinical applications. This paper reviews the T1ρ imaging’s basic physic principles, as well as its application for cartilage imaging and intervertebral disc imaging. Compared to more established T2 relaxation time, it has been shown that T1ρ provides more sensitive detection of proteoglycan (PG) loss at early stages of cartilage degeneration. T1ρ has also been shown to provide more sensitive evaluation of annulus fibrosis (AF) degeneration of the discs. PMID:26807369

  2. Characterization of slow-gelling alginate hydrogels for intervertebral disc tissue-engineering applications.

    PubMed

    Growney Kalaf, Emily A; Flores, Reynaldo; Bledsoe, J Gary; Sell, Scott A

    2016-06-01

    Reversal of intervertebral disc degeneration can have a potentially monumental effect on spinal health. As such, the goal of this research is to create an injectable, cellularized alginate-based nucleus pulposus that will restore disc function; with the primary goal of creating an alginate gel with tailorable rates of gelation to improve functionality over standard CaCl2 crosslinking techniques. Gelation characteristics of 1% sodium alginate were analyzed over various molar concentrations of a 1:2 ratio of CaCO3:glucono-δ-lactone (GDL), with 10% CaCl2 as the control crosslinker. Alginate construct characterization for all concentrations was performed via ultimate and cyclic compressive testing over a 28day degradation period in PBS. Dehydration, swell testing, and albumin release kinetics were determined, and cytotoxicity and cell homogeneity tests showed promise for cellularization strategies. Overall, the 30 and 60mM GDL alginate concentrations presented the most viable option for use in further studies, with a gelation time between 10 and 30min, low hysteresis over control, low percent change in thickness and weight under both PBS degradation and swelling conditions, and stable mechanical properties over 28days in vitro.

  3. Localized strain measurements of the intervertebral disc annulus during biaxial tensile testing.

    PubMed

    Karakolis, Thomas; Callaghan, Jack P

    2015-01-01

    Both inter-lamellar and intra-lamellar failures of the annulus have been described as potential modes of disc herniation. Attempts to characterize initial lamellar failure of the annulus have involved tensile testing of small tissue samples. The purpose of this study was to evaluate a method of measuring local surface strains through image analysis of a tensile test conducted on an isolated sample of annular tissue in order to enhance future studies of intervertebral disc failure. An annulus tissue sample was biaxial strained to 10%. High-resolution images captured the tissue surface throughout testing. Three test conditions were evaluated: submerged, non-submerged and marker. Surface strains were calculated for the two non-marker conditions based on motion of virtual tracking points. Tracking algorithm parameters (grid resolution and template size) were varied to determine the effect on estimated strains. Accuracy of point tracking was assessed through a comparison of the non-marker conditions to a condition involving markers placed on tissue surface. Grid resolution had a larger effect on local strain than template size. Average local strain error ranged from 3% to 9.25% and 0.1% to 2.0%, for the non-submerged and submerged conditions, respectively. Local strain estimation has a relatively high potential for error. Submerging the tissue provided superior strain estimates.

  4. T1ρ magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging.

    PubMed

    Wáng, Yì-Xiáng J; Zhang, Qinwei; Li, Xiaojuan; Chen, Weitian; Ahuja, Anil; Yuan, Jing

    2015-12-01

    T1ρ relaxation time provides a new contrast mechanism that differs from T1- and T2-weighted contrast, and is useful to study low-frequency motional processes and chemical exchange in biological tissues. T1ρ imaging can be performed in the forms of T1ρ-weighted image, T1ρ mapping and T1ρ dispersion. T1ρ imaging, particularly at low spin-lock frequency, is sensitive to B0 and B1 inhomogeneity. Various composite spin-lock pulses have been proposed to alleviate the influence of field inhomogeneity so as to reduce the banding-like spin-lock artifacts. T1ρ imaging could be specific absorption rate (SAR) intensive and time consuming. Efforts to address these issues and speed-up data acquisition are being explored to facilitate wider clinical applications. This paper reviews the T1ρ imaging's basic physic principles, as well as its application for cartilage imaging and intervertebral disc imaging. Compared to more established T2 relaxation time, it has been shown that T1ρ provides more sensitive detection of proteoglycan (PG) loss at early stages of cartilage degeneration. T1ρ has also been shown to provide more sensitive evaluation of annulus fibrosis (AF) degeneration of the discs.

  5. MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis

    PubMed Central

    2012-01-01

    Background Early stages of scoliosis and spondylolisthesis entail changes in the intervertebral disc (IVD) structure and biochemistry. The current clinical use of MR T2-weighted images is limited to visual inspection. Our hypothesis is that the distribution of the MRI signal intensity within the IVD in T2-weighted images depends on the spinal pathology and on its severity. Therefore, this study aims to develop the AMRSID (analysis of MR signal intensity distribution) method to analyze the 3D distribution of the MR signal intensity within the IVD and to evaluate their sensitivity to scoliosis and spondylolisthesis and their severities. Methods This study was realized on 79 adolescents who underwent a MRI acquisition (sagittal T2-weighted images) before their orthopedic or surgical treatment. Five groups were considered: low severity scoliosis (Cobb angle ≤50°), high severity scoliosis (Cobb angles >50°), low severity spondylolisthesis (Meyerding grades I and II), high severity spondylolisthesis (Meyerding grades III, IV and V) and control. The distribution of the MRI signal intensity within the IVD was analyzed using the descriptive statistics of histograms normalized by either cerebrospinal fluid or bone signal intensity, weighted centers and volume ratios. Differences between pathology and severity groups were assessed using one- and two-way ANOVAs. Results There were significant (p < 0.05) variations of indices between scoliosis, spondylolithesis and control groups and between low and high severity groups. The cerebrospinal fluid normalization was able to detect differences between healthy and pathologic IVDs whereas the bone normalization, which reflects both bone and IVD health, detected more differences between the severities of these pathologies. Conclusions This study proves for the first time that changes in the intervertebral disc, non visible to the naked eye on sagittal T2-weighted MR images of the spine, can be detected from specific indices

  6. The effect of sustained compression on oxygen metabolic transport in the intervertebral disc decreases with degenerative changes.

    PubMed

    Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien

    2011-08-01

    Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such

  7. Comparison of cervical disc arthroplasty with anterior cervical discectomy and fusion for the treatment of cervical spondylotic myelopathy.

    PubMed

    Ding, Chen; Hong, Ying; Liu, Hao; Shi, Rui; Song, Yueming; Li, Tao

    2013-06-01

    The clinical outcome of cervical disc arthroplasty for cervical spondylotic myelopathy (CSM) is still controversial. The authors retrospectively compared the intermediate term clinical outcome of cervical disc arthroplasty and traditional anterior cervical discectomy and fusion (ACDF). Seventy-six cases of single-level CSM with a minimum follow-up of two years were retrospectively analyzed. Thirty-seven patients underwent single-level cervical disc arthroplasty (Bryan disc: 12 cases; Prestige LP disc: 25 cases), while the other 39 patients underwent single-level ACDF. Significant improvement in SF-36 physical/ mental component scores and NDI score was found in both groups (p < 0.05); however, the arthroplasty group had significantly greater score improvement at each follow-up time point (p < 0.05). The JOA score and Nurick grade improved significantly at each time point in both groups (p < 0.05), but there were no significant differences between the groups (p > 0.05). The range of motion (surgical level and C2C7) remained unchanged in the arthroplasty group (p > 0.05), whereas it decreased significantly in the ACDF group (p < 0.05). The arthroplasty group had a lower incidence of complications than the ACDF group. The intermediate outcomes of cervical disc arthroplasty compared favourably to those of ACDF. Arthroplasty avoids complications from spinal fusion by preserving mobility.

  8. A retrospective study evaluating the correlation between the severity of intervertebral disc injury and the anteroposterior type of thoracolumbar vertebral fractures

    PubMed Central

    Su, Yunshan; Ren, Dong; Zou, Yan; Lu, Jian; Wang*, Pengcheng

    2016-01-01

    OBJECTIVE: To evaluate the correlation between the severity of intervertebral disc injury and the anteroposterior type of thoracolumbar vertebral fractures. METHODS: Fifty-six cases of thoracolumbar vertebral fractures treated in our trauma center from October 2012 to October 2013 were included in this study. The fractures were classified by the anteroposterior classification, whereas the severity of intervertebral disc injury was evaluated using magnetic resonance imaging. The Spearman correlation coefficient was used to analyze the correlation between the severity of intervertebral disc injury and the anteroposterior type of thoracolumbar fractures, whereas a χ2 test was adopted to measure the variability between different fracture types and upper and lower adjacent disc injuries. RESULTS: The Spearman correlation coefficients between fracture types and the severity of the upper and lower adjacent disc injuries were 0.739 (PU<0.001) and 0.368 (PL=0.005), respectively. It means that the more complex Arbeitsgemeinschaft für Osteosynthesefragen (AO) classifications are the disc injury is more severe. There was also a significant difference in the severity of injury between the upper and lower adjacent discs near the fractured vertebrae (p<0.001). CONCLUSIONS: In thoracolumbar spinal fractures, the severity of the adjacent intervertebral disc injury is positively correlated with the anteroposterior fracture type. The injury primarily involves intervertebral discs near the fractured end plate, with more frequent and severe injuries observed in the upper than in the lower discs. The presence of intervertebral disc injury, along with its severity, may provide useful information during the clinical decision-making process. PMID:27438561

  9. GENIPIN-CROSSLINKED FIBRIN HYDROGELS AS A POTENTIAL ADHESIVE TO AUGMENT INTERVERTEBRAL DISC ANNULUS REPAIR

    PubMed Central

    Schek, R.M.; Michalek, A.J.; Iatridis, J.C.

    2011-01-01

    Treatment of damaged intervertebral discs is a significant clinical problem and, despite advances in the repair and replacement of the nucleus pulposus, there are few effective strategies to restore defects in the annulus fibrosus. An annular repair material should meet three specifications: have a modulus similar to the native annulus tissue, support the growth of disc cells, and maintain adhesion to tissue under physiological strain levels. We hypothesized that a genipin crosslinked fibrin gel could meet these requirements. Our mechanical results showed that genipin crosslinked fibrin gels could be created with a modulus in the range of native annular tissue. We also demonstrated that this material is compatible with the in vitro growth of human disc cells, when genipin:fibrin ratios were 0.25:1 or less, although cell proliferation was slower and cell morphology more rounded than for fibrin alone. Finally, lap tests were performed to evaluate adhesion between fibrin gels and pieces of annular tissue. Specimens created without genipin had poor handling properties and readily delaminated, while genipin crosslinked fibrin gels remained adhered to the tissue pieces at strains exceeding physiological levels and failed at 15–30%. This study demonstrated that genipin crosslinked fibrin gels show promise as a gap-filling adhesive biomaterial with tunable material properties, yet the slow cell proliferation suggests this biomaterial may be best suited as a sealant for small annulus fibrosus defects or as an adhesive to augment large annulus repairs. Future studies will evaluate degradation rate, fatigue behaviors, and long-term biocompatibility. PMID:21503869

  10. Elastic, permeability and swelling properties of human intervertebral disc tissues: A benchmark for tissue engineering.

    PubMed

    Cortes, Daniel H; Jacobs, Nathan T; DeLucca, John F; Elliott, Dawn M

    2014-06-27

    The aim of functional tissue engineering is to repair and replace tissues that have a biomechanical function, i.e., connective orthopaedic tissues. To do this, it is necessary to have accurate benchmarks for the elastic, permeability, and swelling (i.e., biphasic-swelling) properties of native tissues. However, in the case of the intervertebral disc, the biphasic-swelling properties of individual tissues reported in the literature exhibit great variation and even span several orders of magnitude. This variation is probably caused by differences in the testing protocols and the constitutive models used to analyze the data. Therefore, the objective of this study was to measure the human lumbar disc annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplates (CEP) biphasic-swelling properties using a consistent experimental protocol and analyses. The testing protocol was composed of a swelling period followed by multiple confined compression ramps. To analyze the confined compression data, the tissues were modeled using a biphasic-swelling model, which augments the standard biphasic model through the addition of a deformation-dependent osmotic pressure term. This model allows considering the swelling deformations and the contribution of osmotic pressure in the analysis of the experimental data. The swelling stretch was not different between the disc regions (AF: 1.28±0.16; NP: 1.73±0.74; CEP: 1.29±0.26), with a total average of 1.42. The aggregate modulus (Ha) of the extra-fibrillar matrix was higher in the CEP (390kPa) compared to the NP (100kPa) or AF (30kPa). The permeability was very different across tissue regions, with the AF permeability (64 E(-16)m(4)/Ns) higher than the NP and CEP (~5.5 E(-16)m(4)/Ns). Additionally, a normalized time-constant (3000s) for the stress relaxation was similar for all the disc tissues. The properties measured in this study are important as benchmarks for tissue engineering and for modeling the disc's mechanical

  11. Determination and comparison of specifics of nucleus pulposus cells of human intervertebral disc in alginate and chitosan–gelatin scaffolds

    PubMed Central

    Renani, Hamid Bahramian; Ghorbani, Masood; Beni, Batool Hashemibeni; Karimi, Z; Mirhosseini, MM; Zarkesh, H; Kabiri, A

    2012-01-01

    Introduction: Low back pain is a major economical and social problem nowadays. Intervertebral disc herniation and central degeneration of disc are two major reasons of low back pain that occur because of structural impairment of disc. The intervertebral disc contains three parts as follows : Annulus fibrosus, transitional region, and nucleus pulposus, which forms the central nucleus of the disc. The reduction of cell count and extracellular matrix, especially in nucleus pulposus, causes disc degeneration. Different scaffolds (natural and synthetic) have been used for tissue repairing and regeneration of the intervertebral disc in tissue engineering. Most scaffolds have biodegradable and biocompatible characteristics and also prepare a fine condition for proliferation and migration of cells. In this study, proliferation of NP cells of human intervertebral disc compromised in Chitosan-gelatin scaffold with alginate scaffold was studied. Materials and Methods: NP cells derived from nucleus pulposus by collagenase enzymatic hydrolysis. They were derived from patients who undergoing open surgery for discectomy in the Isfahan Alzahra hospital. Chitosan was blended with gelatin and glutaraldehyde was used for cross linking the two polymers. Then, alginate scaffold was prepared. Cellular suspension with 1 × 105 transferred to each scaffold and cultured for 21 days. Cell viability and proliferation investigated by trypan blue and (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Scanning electron microscope (SEM) was used to assert the porosity and to survey structure of scaffold. Results: MTT assay dem1onstrated that cell viability of third day had significant difference in contrast by first day in both scaffolds. Accordingly, there was a significant decreased in cellular viability from day 3 to 21. Results of the cell count showed a punctual elevation cell numbers for alginate scaffold but there was no similar result for chitosan

  12. The Effects of Age, Gender, Ethnicity, and Spinal Level on the Rate of Intervertebral Disc Degeneration. A review of 1712 Intervertebral Discs

    PubMed Central

    Siemionow, Krzysztof; An, Howard; Masuda, Koichi; Andersson, Gunnar; Cs-Szabo, Gabriella

    2010-01-01

    Study Design A gross anatomical and magnetic resonance imaging (MRI) study of intervertebral disc (IVD) degeneration in fresh cadaveric lumbar spines. Objective The purpose of this study was to find the rate of IVD degeneration. Summary of Background Data Age, sex, race, and lumbar level are among some of the factors that play a role in IVD degeneration. The rate at which IVDs degenerate is unknown. Methods Complete lumbar spine segments (T11/12 to S1) were received within 24 hours of death. The nucleus pulposus, annulus fibrosus, cartilaginous and bony end-plate, and the peripheral verterbral body were assessed with MRI and IVD degeneration was graded by two observers from grade 1(nondegenerated) to grade 5(severely degenerated) based on a scale developed by Tanaka et al. The specimens were then sectioned and gross anatomical evaluation was performed according to Thompson et al. Results 433 donors and 1712 IVDs were analyzed. There were 366 Caucasians, 47 Africans, 16 Hispanics, 4 Asian. There were 306 males and 127 females. The age range was 14–81 years, (average 60.5+/−11.3). For donors greater than age 40, the L5/S1 IVD degenerated at a significantly faster rate of 0.043/year compared to 0.031, 0.034, 0.033, 0.027 for L12, L23, L34, L45, respectively. For donors younger than 40, L5/S1 IVD degenerated at a significantly faster rate of 0.141/year compared to 0.033,0.021, 0.031, 0.050 for L12, L23, L34, L45, respectively. Multiple regression analysis revealed that gender had no significant effect on IVD degeneration whereas African ethnicity was associated with lower Thompson score at L12, L23, L34, L45 when compared to Caucasians. Conclusions The relatively early degeneration at L5-S1 in all races and lower Thompson grade in donors of African ethnicity needs further investigation. Factors such as sagittal alignment, facet joint arthritis, and genetics potentially play a role in IVD degeneration. PMID:21217432

  13. A multi-component fiber-reinforced PHEMA-based hydrogel/HAPEX™ device for customized intervertebral disc prosthesis.

    PubMed

    Gloria, Antonio; De Santis, Roberto; Ambrosio, Luigi; Causa, Filippo; Tanner, K Elizabeth

    2011-05-01

    Spinal disease due to intervertebral disc degeneration represents a serious medical problem which affects many people worldwide. Disc arthroplasty may be considered the future ''gold standard'' of back pain treatment, even if problems related to available disc prostheses are considered. Hence, the aim of the present study was to improve the artificial disc technology by proposing the engineering of a pilot-scale device production process for a total multi-component intervertebral disc prosthesis. The device is made up of a poly(2-hydroxyethyl methacrylate)/poly(methyl methacrylate) (PHEMA/PMMA) (80/20 w/w) semi-interpenetrating polymer network (s-IPN) composite hydrogel reinforced with poly(ethylene terephthalate) (PET) fibers as annulus/nucleus substitute, and two hydroxyapatite-reinforced polyethylene composite (HAPEX™) endplates in order to anchor the multi-component device to the vertebral bodies. Static and dynamic-mechanical characterization show appropriate mechanical behavior. An example of engineering of a suitable pilot-scale device production process is also proposed in order to manufacture custom made implants.

  14. The effects of short-term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc.

    PubMed

    MacLean, Jeffery J; Lee, Cynthia R; Alini, Mauro; Iatridis, James C

    2005-09-01

    The goal of this study was to determine the time-dependent response of the intervertebral disc cells to in vivo dynamic compression. Forty-seven skeletally mature Wistar rats (>12 months old) were instrumented with an Ilizarov-type device spanning caudal disc 8-9. Using a load magnitude (1 MPa) and frequency (1.0 Hz) that were previously shown to significantly alter mRNA levels in the disc, the effects of 0.5 and 4 h of loading were investigated and compared to a sham group and our previous 2 h results. Annulus and nucleus tissue of loaded (c8-9) and internal control discs (c6-7 and c10-11) were separately analyzed by real-time RT-PCR for levels of mRNA coding for various anabolic (collagen-1A1, collagen-2A1, aggrecan) and catabolic (MMP-3, MMP-13, ADAMTs-4) proteins. In the annulus, mRNA levels increased for Collagen types I & II, and MMP 3 & 13 with increasing load duration. In contrast, the nucleus had the largest increases in aggrecan, ADAMTs-4, MMP-3 and MMP-13 after 2 h of loading, with aggrecan and MMP-13 mRNA levels returning to control values after 4 h of loading. Taken in context with our previous studies, we conclude that intervertebral disc cells from the nucleus and annulus have distinct responses to dynamic mechanical compression in vivo with sensitivity to compression magnitude, frequency and duration.

  15. Application of the polynomial chaos expansion to approximate the homogenised response of the intervertebral disc.

    PubMed

    Karajan, N; Otto, D; Oladyshkin, S; Ehlers, W

    2014-10-01

    A possibility to simulate the mechanical behaviour of the human spine is given by modelling the stiffer structures, i.e. the vertebrae, as a discrete multi-body system (MBS), whereas the softer connecting tissue, i.e. the softer intervertebral discs (IVD), is represented in a continuum-mechanical sense using the finite-element method (FEM). From a modelling point of view, the mechanical behaviour of the IVD can be included into the MBS in two different ways. They can either be computed online in a so-called co-simulation of a MBS and a FEM or offline in a pre-computation step, where a representation of the discrete mechanical response of the IVD needs to be defined in terms of the applied degrees of freedom (DOF) of the MBS. For both methods, an appropriate homogenisation step needs to be applied to obtain the discrete mechanical response of the IVD, i.e. the resulting forces and moments. The goal of this paper was to present an efficient method to approximate the mechanical response of an IVD in an offline computation. In a previous paper (Karajan et al. in Biomech Model Mechanobiol 12(3):453-466, 2012), it was proven that a cubic polynomial for the homogenised forces and moments of the FE model is a suitable choice to approximate the purely elastic response as a coupled function of the DOF of the MBS. In this contribution, the polynomial chaos expansion (PCE) is applied to generate these high-dimensional polynomials. Following this, the main challenge is to determine suitable deformation states of the IVD for pre-computation, such that the polynomials can be constructed with high accuracy and low numerical cost. For the sake of a simple verification, the coupling method and the PCE are applied to the same simplified motion segment of the spine as was used in the previous paper, i.e. two cylindrical vertebrae and a cylindrical IVD in between. In a next step, the loading rates are included as variables in the polynomial response functions to account for a more

  16. Vitamin D Receptor Gene, Matrix Metalloproteinase 3 Polymorphisms and the Risk of Intervertebral Disc Degeneration Susceptibility: Meta-Analysis

    PubMed Central

    Huang, Yongjing; Zhao, Shujie; Xu, Nanwei

    2016-01-01

    Several studies have evaluated the association between vitamin D receptor, matrix metalloproteinase 3 (MMP-3) polymorphisms and the risk of intervertebral disc degeneration susceptibility. The findings were inconsistent. This meta-analysis aimed to systematically assess the association between vitamin D receptor, MMP-3 polymorphisms and the risk of intervertebral disc degeneration susceptibility. A search of various databases was done covering all papers published until December 31th, 2014. Eight, 4, 3 studies were finally included that addressed the risk of intervertebral disc degeneration susceptibility and vitamin D receptor FokI (rs2228570), ApaI (rs7975232), and MMP-3 (rs731236) polymorphisms, respectively. FokI (f vs. F: summary odds ratio [OR], 1.13; 95% confidence interval [CI], 0.76–1.69; ff vs. FF: OR, 1.02; 95% CI, 0.59–1.77; ff vs. Ff/FF: OR, 1.05; 95% CI, 0.70–1.58), ApaI (a vs. A: OR, 0.73; 95% CI, 0.45–1.19; aa vs. AA: OR, 0.53; 95% CI, 0.22–1.25 p=0.14; aa vs. AA/Aa: OR, 0.69; 95% CI, 0.53–0.89) in the vitamin D receptor gene and MMP3 polymorphisms (5A vs. 6A: OR, 1.92; 95% CI, 0.77–4.80; 5A5A vs. 6A6A: OR, 2.17; 95% CI, 0.75–6.24; 5A5A vs. 5A6A/6A6A: OR, 1.58; 95% CI, 0.72–3.44) were not obviously associated with risk of intervertebral disc degeneration susceptibility. FokI, ApaI polymorphisms in the vitamin D receptor gene and MMP-3 polymorphism are not obvious risk factors for intervertebral disc degeneration susceptibility. PMID:27790329

  17. Mixed reality simulation of rasping procedure in artificial cervical disc replacement (ACDR) surgery

    PubMed Central

    2010-01-01

    process called registration. This issue was overcome by a two-way (virtual object to real domain and real domain to virtual object) semi-automatic registration method. Conclusions The applicability of the VICON MR setting for the ACDR surgical simulator is demonstrated. The main stream problems encountered in MR surgical simulator development are addressed. First, an effective environment for MR surgical development is constructed. Second, the strain and the stress intensities and critical forces are simulated under the various rasp instrument loadings with impacts that are applied on intervertebral surfaces of the anterior vertebrae throughout the rasping procedure. Third, two approaches are introduced to solve the registration problem in MR setting. Results show that our system creates an effective environment for surgical simulation development and solves tedious and time-consuming registration problems caused by misalignments. Further, the MR ACDR surgery simulator was tested by 5 different physicians who found that the MR simulator is effective enough to teach the anatomical details of cervical discs and to grasp the basics of the ACDR surgery and rasping procedure PMID:20946594

  18. Hybrid Surgery Versus Anterior Cervical Discectomy and Fusion in Multilevel Cervical Disc Diseases

    PubMed Central

    Zhang, Jianfeng; Meng, Fanxin; Ding, Yan; Li, Jie; Han, Jian; Zhang, Xintao; Dong, Wei

    2016-01-01

    Abstract To investigate the outcomes and reliability of hybrid surgery (HS) versus anterior cervical discectomy and fusion (ACDF) for the treatment of multilevel cervical spondylosis and disc diseases. Hybrid surgery, combining cervical disc arthroplasty (CDA) with fusion, is a novel treatment to multilevel cervical degenerated disc disease in recent years. However, the effect and reliability of HS are still unclear compared with ACDF. To investigate the studies of HS versus ACDF in patients with multilevel cervical disease, electronic databases (Medline, Embase, Pubmed, Cochrane library, and Cochrane Central Register of Controlled Trials) were searched. Studies were included when they compared HS with ACDF and reported at least one of the following outcomes: functionality, neck pain, arm pain, cervical range of motion (ROM), quality of life, and incidence of complications. No language restrictions were used. Two authors independently assessed the methodological quality of included studies and extracted the relevant data. Seven clinical controlled trials were included in this study. Two trials were prospective and the other 5 were retrospective. The results of the meta-analysis indicated that HS achieved better recovery of NDI score (P = 0.038) and similar recovery of VAS score (P = 0.058) compared with ACDF at 2 years follow-up. Moreover, the total cervical ROM (C2–C7) after HS was preserved significantly more than the cervical ROM after ACDF (P = 0.000) at 2 years follow-up. Notably, the compensatory increase of the ROM of superior and inferior adjacent segments was significant in ACDF groups at 2-year follow-up (P < 0.01), compared with HS. The results demonstrate that HS provides equivalent outcomes and functional recovery for cervical disc diseases, and significantly better preservation of cervical ROM compared with ACDF in 2-year follow-up. This suggests the HS is an effective alternative invention for the treatment of multilevel cervical

  19. Systemic Delivery of Bone Marrow Mesenchymal Stem Cells for In Situ Intervertebral Disc Regeneration.

    PubMed

    Cunha, Carla; Almeida, Catarina R; Almeida, Maria Inês; Silva, Andreia M; Molinos, Maria; Lamas, Sofia; Pereira, Catarina L; Teixeira, Graciosa Q; Monteiro, António T; Santos, Susana G; Gonçalves, Raquel M; Barbosa, Mário A

    2017-03-01

    Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site. MSC transplantation was performed 24 hours after injury, in parallel with dermal fibroblasts as a control; 2 weeks after transplantation, animals were killed. Disc height index and histological grading score indicated less degeneration for the MSC-transplanted group, with no significant changes in extracellular matrix composition. Remarkably, MSC transplantation resulted in local downregulation of the hypoxia responsive GLUT-1 and in significantly less herniation, with higher amounts of Pax5+ B lymphocytes and no alterations in CD68+ macrophages within the hernia. The systemic immune response was analyzed in the blood, draining lymph nodes, and spleen by flow cytometry and in the plasma by cytokine array. Results suggest an immunoregulatory effect in the MSC-transplanted animals compared with control groups, with an increase in MHC class II+ and CD4+ cells, and also upregulation of the cytokines IL-2, IL-4, IL-6, and IL-10, and downregulation of the cytokines IL-13 and TNF-α. Overall, our results indicate a beneficial effect of systemically transplanted MSCs on in situ IVD regeneration and highlight the complex interplay between stromal cells and cells of the immune system in achieving successful tissue regeneration. Stem Cells Translational Medicine 2017;6:1029-1039.

  20. Differential expression of galectin-1 and its interactions with cells and laminins in the intervertebral disc.

    PubMed

    Jing, Liufang; So, Stephen; Lim, Shaun W; Richardson, William J; Fitch, Robert D; Setton, Lori A; Chen, Jun

    2012-12-01

    Galectin-1 (Gal-1), an endogenous β-galactoside-binding protein, binds to laminins, which are highly expressed in the nucleus pulposus (NP) of the intervertebral disc (IVD). The objective of this study is to evaluate the expression of Gal-1 protein in IVD tissues during aging and the effect of Gal-1 on IVD cell adhesion to laminins. Tissues from rat, porcine, and human (scoliosis or disc degeneration) IVDs were used to evaluate Gal-1 expression via immunostaining, RT-PCR, and Western blot analysis. Attachment of isolated IVD cells (porcine and human) on select laminin isoforms (LM-111 and LM-511) was compared with/without pre-incubation with exogenous Gal-1. A biotinylated Gal-1(B-Gal-1) was used to evaluate for binding to IVD cells and to select for IVD cells by magnetic activated cell sorting (MACS). NP cells expressed high levels of Gal-1 protein as compared to anulus fibrosus (AF) cells in immature tissues, while exogenous Gal-1 increased both NP and AF cell attachment to laminins and exhibited a similar binding to both cell types in vitro. With aging, Gal-1 levels in NP tissue appeared to decrease. In addition, incubation with B-Gal-1 was able to promote the retention of more than 50% of IVD cells via MACS. Our results provide new findings for the presence and functional role of Gal-1 within IVDs. Similar staining patterns for Gal-1 and LM-511 in IVD tissue suggest that Gal-1 may serve as an adhesion molecule to interact with both cells and laminins. This MACS protocol may be useful for selecting pure IVD cells from mixed cells of pathological tissue.

  1. IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells

    PubMed Central

    Wu, Xinghuo; Song, Yu; Liu, Wei; Wang, Kun; Gao, Yong; Li, Shuai; Duan, Zhenfeng; Shao, Zengwu; Yang, Shuhua; Yang, Cao

    2017-01-01

    The pathogenic process of intervertebral disc degeneration (IDD) is characterized by imbalance in the extracellular matrix (ECM) metabolism. Nucleus pulposus (NP) cells have important roles in maintaining the proper structure and tissue homeostasis of disc ECM. These cells need adequate supply of glucose and oxygen. Islet amyloid polypeptide (IAPP) exerts its biological effects by regulating glucose metabolism. The purpose of this study was to investigate the expression of IAPP in degenerated IVD tissue, and IAPP modulation of ECM metabolism in human NP cells, especially the crosstalk mechanism between apoptosis and autophagy in these cells. We found that the expression of IAPP and Calcr-RAMP decreased considerably during IDD progression, along with the decrease in the expression of AG, BG, and Col2A1. Induction of IAPP in NP cells by transfection with pLV-IAPP enhanced the synthesis of aggrecan and Col2A1 and attenuated the expression of pro-inflammatory factors, tumor necrosis factor (TNF)-α, and interleukin (IL)-1. Upregulation of IAPP also affected the expression of the catabolic markers—matrix metalloproteinases (MMPs) 3, 9 and 13 and ADAMTS 4 and 5. Downregulation of IAPP by siRNA inhibited the expression of anabolic genes but increased the expression of catabolic genes and inflammatory factors. The expressions of autophagic and apoptotic markers in NP cells transfected with pLV-IAPP were upregulated, including BECLIN1, ATG5, ATG7, LC3 II/I and Bcl-2, while significantly increase in the expression of Bax and Caspase-3 in NP cells transfected with pLV-siIAPP. Mechanistically, PI3K/AKT-mTOR and p38/JNK MAPK signal pathways were involved. We propose that IAPP might play a pivotal role in the development of IDD, by regulating ECM metabolism and controlling the crosstalk between apoptosis and autophagy in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD. PMID:28149534

  2. A PHASED REHABILITATION PROTOCOL FOR ATHLETES WITH LUMBAR INTERVERTEBRAL DISC HERNIATION

    PubMed Central

    VanGelder, Leonard H.; Vaughn, Daniel W.

    2013-01-01

    Conservative non-surgical management of a herniated lumbar intervertebral disc (HLD) in athletes is a complex task due to the dramatic forces imparted on the spine during sport participation. The demands placed upon the athlete during rehabilitation and return to sport are unique not only from a sport specific perspective, but also regarding return to the sport strength and conditioning programs utilized for sport preparation. Many prescriptions fail to address postural and motor control faults specific to athletic development, which may prevent full return to sport after suffering a HLD or predispose the athlete to future exacerbations of a HLD. Strength exercises involving squatting, deadlifting, and Olympic power lifts are large components of the typical athlete's conditioning program, therefore some progressions are provided to address potential underlying problems in the athlete's technique that may have contributed to their HLD in the first place. The purpose of this clinical commentary is to propose a framework for rehabilitation that is built around the phases of healing of the disc. Phase I: Non-Rotational/Non-Flexion Phase (Acute Inflammatory Phase), Phase II: Counter rotation/Flexion Phase (Repair Phase), Phase III: Rotational Phase/Power development (Remodeling Phase), and Phase IV: Full return to sport. This clinical commentary provides a theoretical basis for these phases based on available literature as well as reviewing many popular current practice trends in the management of an HLD. The authors recognize the limits of any general exercise rehabilitation recommendation with regard to return to sport, as well as any general strength and conditioning program. It is vital that an individual assessment and prescription is made for every athlete which reviews and addresses movement in all planes of motion under all necessary extrinsic and intrinsic demands to that athlete. Level of Evidence: 5 PMID:24175134

  3. Organ culture bioreactors--platforms to study human intervertebral disc degeneration and regenerative therapy.

    PubMed

    Gantenbein, Benjamin; Illien-Jünger, Svenja; Chan, Samantha C W; Walser, Jochen; Haglund, Lisbet; Ferguson, Stephen J; Iatridis, James C; Grad, Sibylle

    2015-01-01

    In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of "smart" biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments.

  4. Differential response of nucleus pulposus intervertebral disc cells to high salt, sorbitol, and urea.

    PubMed

    Mavrogonatou, Eleni; Kletsas, Dimitris

    2012-03-01

    Nucleus pulposus intervertebral disc cells are routinely confronted with high osmolality in their microenvironment and respond to this stress in vitro by regulating cell cycle progression and by activating a DNA repair machinery in order to counteract its genotoxic effect. In the present study, we attempted to identify the origin of this osmo-regulatory response, by using an ionic NaCl/KCl solution, the compatible osmolyte sorbitol, and the readily permeant urea. High salt and sorbitol were found to activate similar molecular pathways, including the p38 MAPK and the p53-p21(WAF1)-pRb axis, that were not stimulated by high urea. On the other hand, only high urea led to the phosphorylation of ERKs and JNKs. Furthermore, salt- and sorbitol-treated cells were able to phosphorylate histone H2A.X on Ser139, in contrast to cells exposed to urea, indicating a common mechanism for DNA repair, which was achieved by a p53-dependent activation of the G1 checkpoint by both solutes. DNA repair, as directly measured by a host cell reactivation assay, occurred under conditions of hyperosmolar salt and sorbitol, although to a lesser extent in sorbitol-treated cells than in cells exposed to high salinity. Taken as a whole, our findings suggest that the hyperosmolality-provoked DNA damage and the responses of nucleus pulposus cells induced by this genotoxic stress most probably originate from cell volume alterations mediated by hypertonicity and not from increased intracellular ionic concentration.

  5. Sesamin inhibits lipopolysaccharide-induced inflammation and extracellular matrix catabolism in rat intervertebral disc.

    PubMed

    Li, Kang; Li, Yan; Xu, Bo; Mao, Lu; Zhao, Jie

    2016-09-01

    Intervertebral disc (IVD) degeneration contributes to most spinal degenerative diseases, while treatment inhibiting IVD degeneration is still in the experimental stage. Sesamin, a bioactive component extracted from sesame, has been reported to exert chondroprotective and anti-inflammatory effects. Here, we analyzed the anti-inflammatory and anti-catabolic effects of sesamin on rat IVD in vitro and ex vivo. Results show that sesamin significantly inhibits the lipopolysaccharide (LPS)-induced expression of catabolic enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5) and inflammation factors (IL-1β, TNF-α, iNOS, NO, COX-2, PGE2) in a dose-dependent manner in vitro. It is also proven that migration of macrophages induced by LPS can be inhibited by treatment with sesamin. Organ culture experiments demonstrate that sesamin protects the IVD from LPS-induced depletion of the extracellular matrix ex vivo. Moreover, sesamin suppresses LPS-induced activation of the mitogen-activated protein kinase (MAPK) pathway through inhibiting phosphorylation of JNK, the common downstream signaling pathway of LPS and IL-1β, which may be the potential mechanism of the effects of sesamin. In light of our results, sesamin protects the IVD from inflammation and extracellular matrix catabolism, presenting positive prospects in the treatment of IVD degenerative diseases.

  6. Interleukin 1 Polymorphisms Contribute to Intervertebral Disc Degeneration Risk: A Meta-Analysis

    PubMed Central

    Fu, Changfeng; Xu, Feng; Chen, Yong; Wang, Zhenyu; Liu, Yi

    2016-01-01

    Objective We performed a meta-analysis to assess association between interleukin 1 (IL-1) polymorphisms and the risk of Intervertebral Disc Degeneration (IDD). Background A series of studies have investigated the association between common single nucleotide polymorphisms in IL-1 and IDD risk; however, the overall results are inconclusive. Methods Two independent investigators conducted a systematic search for relevant available studies. Allele frequencies were extracted from each study. The association between the IL-1α (+889C/T) or IL-1β (+3954C/T) polymorphism and IDD risk was measured by odds ratios (OR) with 95% confidence intervals (95% CI). Results Five and six studies, respectively, were ultimately included in the meta-analysis for the IL-1α (+889C/T) and IL-1β (+3954C/T) polymorphism. The combined results showed that the IL-1α (+889C/T) polymorphism was significantly associated with increased susceptibility to IDD, particularly in Caucasians (TT versus CC: OR = 2.95, 95% CI: 1.45, 6.04; Pheterogeneity = 0.82; TT versus CC/CT: OR = 2.29, 95% CI: 1.18, 4.47; Pheterogeneity = 0.20). In contrast, the IL-1β (+3954C/T) polymorphism showed a trend towards increased risk in Caucasians but no association in Asians. Conclusion This meta-analysis suggested that the IL-1α (+889C/T) polymorphism is significantly associated with risk of IDD, especially in Caucasian populations. PMID:27253397

  7. Genome-Wide Identification of Long Noncoding RNAs in Human Intervertebral Disc Degeneration by RNA Sequencing

    PubMed Central

    Zhao, Bo; Lu, Minjuan; Wang, Dong; Li, Haopeng

    2016-01-01

    Long noncoding RNAs (lncRNAs) are emerging as crucial players in a myriad of biological processes. However, the precise mechanism and functions of most lncRNAs are poorly characterized. In this study, we presented genome-wide identification of lncRNAs in the patients with intervertebral disc degeneration (IDD) and spinal cord injury (control) using RNA sequencing (RNA-seq). A total of 124.6 million raw reads were yielded using Hiseq 2500 platform and approximately 88% clean reads could be aligned to human reference genome in both IDD and control groups. RNA-seq profiling indicated that 1,854 lncRNAs were differentially expressed (log2 fold change ≥ 1 or ≤−1, p < 0.05), in which 1,530 could potentially target 6,386 genes via cis-regulatory effects. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for these target genes suggested that lncRNAs were involved in diverse pathways, such as lysosome, focal adhesion, and MAPK signaling. In addition, a competing endogenous RNA (ceRNA) network was constructed for analyzing the function of lncRNAs. Further, quantitative real time PCR (qRT-PCR) was used to confirm the differentially expressed lncRNAs and ceRNA network. In conclusion, our results present the first global identification of lncRNAs in IDD and may provide candidate diagnostic biomarkers for IDD treatment. PMID:28097131

  8. The heterogeneity of the non-aggregating proteoglycans of the human intervertebral disc.

    PubMed Central

    DiFabio, J L; Pearce, R H; Caterson, B; Hughes, H

    1987-01-01

    Non-aggregating proteoglycans of differing average hydrodynamic volumes were prepared from nuclei pulposi and anuli fibrosi of three human lumbar spines and characterized by biochemical and immunochemical analyses. The hexose-to-hexuronate and protein-to-hexuronate ratios increased with decreasing hydrodynamic volume. Analysis by composite agarose/polyacrylamide-gel electrophoresis has demonstrated two aggregating subpopulations [McDevitt, Jahnke & Green (1982) Trans. Annu. Meet. Orthop. Res. Soc. 7, 50]. In the present study, electrophoresis of the non-aggregating pools has shown three additional subpopulations, here named bands III, IV and V. The two smallest proteoglycan pools from each tissue contained two and three components respectively. These components were isolated by preparative electrophoresis and analysed. Band III was a proteoglycan richer in keratan sulphate than in chondroitin sulphate; band IV was a proteoglycan richer in chondroitin sulphate than in keratan sulphate; band V contained only chondroitin sulphate. Unsaturated disaccharides prepared from the chondroitin sulphate of all bands were predominantly 6-sulphated, with only 5-15% 4-sulphated. The molecular masses of the chondroitin sulphate and keratan sulphate did not differ between the bands. The amino acid composition of band III differed from that of band IV. Thus three distinct subpopulations of non-aggregating proteoglycan were demonstrated in the human intervertebral disc. PMID:3117036

  9. The Involvement of Protease Nexin-1 (PN1) in the Pathogenesis of Intervertebral Disc (IVD) Degeneration

    PubMed Central

    Wu, Xinghuo; Liu, Wei; Duan, Zhenfeng; Gao, Yong; Li, Shuai; Wang, Kun; Song, Yu; Shao, Zengwu; Yang, Shuhua; Yang, Cao

    2016-01-01

    Protease nexin-1 (PN-1) is a serine protease inhibitor belonging to the serpin superfamily. This study was undertaken to investigate the regulatory role of PN-1 in the pathogenesis of intervertebral disk (IVD) degeneration. Expression of PN-1 was detected in human IVD tissue of varying grades. Expression of both PN-1 mRNA and protein was significantly decreased in degenerated IVD, and the expression levels of PN-1 were correlated with the grade of disc degeneration. Moreover, a decrease in PN-1 expression in primary NP cells was confirmed. On induction by IL-1β, the expression of PN-1 in NP cells was decreased at day 7, 14, and 21, as shown by western blot analysis and immunofluorescence staining. PN-1 administration decreased IL-1β-induced MMPs and ADAMTS production and the loss of Agg and Col II in NP cell cultures through the ERK1/2/NF-kB signaling pathway. The changes in PN-1 expression are involved in the pathogenesis of IVD degeneration. Our findings indicate that PN-1 administration could antagonize IL-1β-induced MMPs and ADAMTS, potentially preventing degeneration of IVD tissue. This study also revealed new insights into the regulation of PN-1 expression via the ERK1/2/NF-kB signaling pathway and the role of PN-1 in the pathogenesis of IVD degeneration. PMID:27460424

  10. Dynamic-mechanical properties of a novel composite intervertebral disc prosthesis.

    PubMed

    Gloria, Antonio; Causa, Filippo; De Santis, Roberto; Netti, Paolo Antonio; Ambrosio, Luigi

    2007-11-01

    Over the past years, a tremendous effort has been made to develop an intervertebral disc (IVD) prosthesis with suitable biological, mechanical and transport properties. However, it has been frequently reported that current prostheses undergo failure mainly due to the mismatch between the mechanical properties of the conventional device and the spine segment to be replaced. The aim of the present work was to develop a poly(2-hydroxyethyl methacrylate)/poly(methyl methacrylate) (PHEMA/PMMA) (80/20 w/w) semi-interpenetrating polymer network (s-IPN) composite hydrogel reinforced with poly(ethylene terephthalate) (PET) fibres, and to investigate the static and dynamic mechanical properties. Filament winding and moulding technologies were employed to obtain the composite IVD prostheses with the unique complex structure that is peculiar to the natural IVD. The compressive properties analysis showed the typical J-shaped stress-strain curve which is displayed by natural IVDs. Compressive modulus varied from 84 to 120 MPa, as a function of the strain rate, and stress was higher than 10 MPa. These values are in the range of those of the natural lumbar IVDs. No failure of the prostheses has occurred during fatigue test performed for ten million cycles in physiological solution. Dynamic mechanical tests have confirmed the composite IVD prostheses exhibited appropriate viscoelastic properties.

  11. Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

    PubMed Central

    Tao, Hao; Lin, Yazhou; Zhang, Guoqing; Gu, Rui; Chen, Bohua

    2016-01-01

    Allogeneic bone marrow mesenchymal stem cell (BMSC) transplantation has been investigated worldwide. However, few reports have addressed the survival status of human BMSCs in the intervertebral discs (IVDs) in vivo following transplantation. The current study aimed to observe the survival status of human BMSCs in rabbit IVDs. The IVDs of 15 New Zealand white rabbits were divided into three groups: Punctured blank control group (L1-2); punctured physiological saline control group (L2-3); and punctured human BMSCs transfected with green fluorescent protein (GFP) group (L3-4, L4-5 and L5-6). One, 2, 4, 6 and 8 weeks after transplantation the IVDs were removed and a fluorescence microscope was used to observe the density of GFP-positive human BMSCs. The results indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). Thus, it was identified that human BMSCs were able to survive in the rabbit IVDs for 8 weeks. PMID:27588177

  12. A developmental transcriptomic analysis of Pax1 and Pax9 in embryonic intervertebral disc development

    PubMed Central

    Sivakamasundari, V.; Kraus, Petra; Sun, Wenjie; Hu, Xiaoming; Lim, Siew Lan; Prabhakar, Shyam

    2017-01-01

    ABSTRACT Pax1 and Pax9 play redundant, synergistic functions in the patterning and differentiation of the sclerotomal cells that give rise to the vertebral bodies and intervertebral discs (IVD) of the axial skeleton. They are conserved in mice and humans, whereby mutation/deficiency of human PAX1/PAX9 has been associated with kyphoscoliosis. By combining cell-type-specific transcriptome and ChIP-sequencing data, we identified the roles of Pax1/Pax9 in cell proliferation, cartilage development and collagen fibrillogenesis, which are vital in early IVD morphogenesis. Pax1 is up-regulated in the absence of Pax9, while Pax9 is unaffected by the loss of Pax1/Pax9. We identified the targets compensated by a single- or double-copy of Pax9. They positively regulate many of the cartilage genes known to be regulated by Sox5/Sox6/Sox9 and are connected to Sox5/Sox6 by a negative feedback loop. Pax1/Pax9 are intertwined with BMP and TGF-B pathways and we propose they initiate expression of chondrogenic genes during early IVD differentiation and subsequently become restricted to the outer annulus by the negative feedback mechanism. Our findings highlight how early IVD development is regulated spatio-temporally and have implications for understanding kyphoscoliosis. PMID:28011632

  13. Small leucine-rich proteoglycans (SLRPs): characteristics and function in the intervertebral disc.

    PubMed

    Chen, Lili; Liao, Jingwen; Klineberg, Eric; Leung, Victor Yl; Huang, Shishu

    2017-03-01

    The intervertebral disc (IVD) is responsible for normal spinal motion and load distribution. However, degeneration may occur due to age- and non-age-related processes and is primarily characterized by a reduction in the number of chondrocyte-like cells and abnormal extracellular matrix (ECM) structure in the nucleus pulposus. Although IVD progenitor cells have been identified, the local microenvironment components regulating the behaviour of these progenitor cell populations remain unknown. Small leucine-rich proteoglycans (SLRPs) are bioactive components of the ECM associated with fibrillogenesis, cellular growth and apoptosis and tissue remodelling. SLRPs support the survival of IVD progenitor cells under hypoxic conditions via the activation of specific hypoxia-inducible factors. Additionally, SLRPs deficiency (biglycan) in knockout mice is sufficient to accelerate the IVD degenerative process. These data suggest that SLRPs play an important role in the homeostasis of IVD. Given their specific properties and physiological functions, we propose a role of SLRPs in IVD degeneration and potential application in its regeneration. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Acid-sensing ion channel 2 (asic 2) and trkb interrelationships within the intervertebral disc

    PubMed Central

    Cuesta, Antonio; Viña, Eliseo; Cabo, Roberto; Vázquez, Gorka; Cobo, Ramón; García-Suárez, Olivia; García-Cosamalón, José; Vega, José A

    2015-01-01

    The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. They express acid-sensing ion channels (ASICs), gated by extracellular protons and mechanical forces, as well as neurotrophins and their signalling receptors. In the nervous tissues some neurotrophins regulate the expression of ASICs. The expression of ASIC2 and TrkB in human normal and degenerated IVD was assessed using quantitative-PCR, Western blot, and immunohistochemistry. Moreover, we investigated immunohistochemically the expression of ASIC2 in the IVD of TrkB-deficient mice. ASIC2 and TrkB mRNAs were found in normal human IVD and both increased significantly in degenerated IVD. ASIC2 and TrkB proteins were also found co-localized in a variable percentage of cells, being significantly higher in degenerated IVD than in controls. The murine IVD displayed ASIC2 immunoreactivity which was absent in the IVD of TrkB-deficient mice. Present results demonstrate the occurrence of ASIC2 and TrkB in the human IVD, and the increased expression of both in pathological IVD suggest their involvement in IVD degeneration. These data also suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression, and therefore in mechanisms by which the IVD cells accommodate to low pH and hypertonicity. PMID:26617738

  15. Thoracic Infectious Spondylitis After Surgical Treatments of Herniated Lumbar Intervertebral Disc

    PubMed Central

    Kim, Jin-Hyun; Kang, Jung-Il; Kim, Min Jeong; Lee, Jongmin; Lee, In-Sik; Jung, Heeyoune

    2013-01-01

    The postoperative infectious spondylitis has been reported to occur among every 1% to 12%. It is difficult to early diagnose in some cases. If the diagnosis is delayed, it can be a life-threatening condition. We report a 32-year-old male patient with postoperative infectious spondylitis. He had surgical treatments for traumatic intervertebral disc herniations in L3-4 and L4-5. Three weeks after surgery, he complained for fever and paraplegia. Cervicothoracic magnetic resonance imaging showed the collapsed T2 and T3 vertebral body with changes of bone marrow signal intensity. Moreover, it showed anterior and posterior epidural masses causing spinal cord compressions which suggested infectious spondylitis. After the use of antibiotics and surgical decompressions T2-T3, his general conditions were improved and muscle power of lower extremities began to be gradually restored. However, we could not identify the exact organisms that may be the cause of infectious spondylitis. It could be important that the infectious spondylitis, which is presented away from the primary operative level, should be observed in patients with fevers of unknown origin and paraplegia. PMID:24236263

  16. In-situ photopolymerized and monitored implants: successful application to an intervertebral disc replacement

    NASA Astrophysics Data System (ADS)

    Schmocker, Andreas M.; Khoushabi, Azadeh; Bourban, Pierre-Etienne; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

    2016-02-01

    Photopolymerization is a common method to harden materials initially in a liquid state. A surgeon can directly trigger the solidification of a dental implant or a bone or tissue filler by using ultra-violet light. Traditionally, photopolymerization has been used mainly in dentistry. Over the last decade advances in material development including a wide range of biocompatible gel- and cement-systems open up a new avenue for in-situ photopolymerization. We designed a miniaturized light probe where a photoactive material can be 1) mixed, pressurized and injected 2) photopolymerized or photoactivated and 3) monitored during the chemical reaction. The device enables surgeries to be conducted through a hole smaller than 500 μm in diameter. Using a combination of Raman and fluorescence spectroscopy, the current state of the photopolymerization was inferred and monitored in real time within an in-vitro tissue model. It was also possible to determine roughly the position of the probe within the tissue cavity by analysing the fluorescence signal. Using the technique hydrogels were successfully implanted into a bovine intervertebral disc model. Mechanical tests could not obstruct the functionality of the implant. Finally, the device was also used for other application such as the implantation of a hydrogel into an aneurysm tissue cavity which will be presented at the conference.

  17. Numerical exploration of the combined effect of nutrient supply, tissue condition and deformation in the intervertebral disc.

    PubMed

    Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien

    2014-04-11

    Novel strategies to heal discogenic low back pain could highly benefit from comprehensive biophysical studies that consider both mechanical and biological factors involved in intervertebral disc degeneration. A decrease in nutrient availability at the bone-disc interface has been indicated as a relevant risk factor and as a possible initiator of cell death processes. Mechanical behaviour of both healthy and degenerated discs could highly interact with cell death in these compromised situations. In the present study, a mechano-transport finite element model was used to investigate the nature of mechanical effects on cell death processes via load-induced metabolic transport variations. Cycles of static sustained compression were chosen to simulate daily human activity. Healthy and degenerated cases were simulated as well as a reduced supply of solutes and an increase in solute exchange area at the bone-disc interface. Results showed that a reduction in metabolite concentrations at the bone-disc boundaries induced cell death, even when the increased exchange area was simulated. Slight local mechanical enhancements of glucose in the disc centre were capable of decelerating cell death but occurred only with healthy mechanical properties. However, mechanical deformations were responsible for a worsening in terms of cell death in the inner annulus, a disadvantaged zone far from the boundary supply with both an increased cell demand and a strain-dependent decrease of diffusivity. Such adverse mechanical effects were more accentuated when degenerative properties were simulated. Overall, this study paves the way for the use of biophysical models for a more integrated understanding of intervertebral disc pathophysiology.

  18. [Traumatic cervical disc prolapse with severe neurological impact].

    PubMed

    Knudsen, Roland; Gundtoft, Per

    2014-12-15

    A 51-year-old male drove into a ditch on his scooter. Immediately after the trauma the patient complained of neck pain and decreased ability to feel and move his extremities. An initial trauma computed tomography (CT) of the columna showed normal conditions. Because the patient had neurological deficiencies, magnetic resonance imaging of the columna was performed 12 days later, and a disc prolapse at the C3/C4 level with spinal cord compression was visible. Despite decompression the patient did not recover. Traumatic cervical disc prolapse is a rare and positionally dangerous condition, which can be present despite a CT showing normal conditions.

  19. Intervertebral disc regeneration using platelet-rich plasma-containing bone marrow-derived mesenchymal stem cells: A preliminary investigation

    PubMed Central

    WANG, SHAN-ZHENG; JIN, JI-YANG; GUO, YU-DONG; MA, LIANG-YU; CHANG, QING; PENG, XIN-GUI; GUO, FANG-FANG; ZHANG, HAI-XIANG; HU, XIN-FENG; WANG, CHEN

    2016-01-01

    Platelet-rich plasma (PRP) is a promising strategy for intervertebral disc degeneration (IDD). However, the short half-life of growth factors released from PRP cannot continuously stimulate the degenerated discs. Thus, the present study hypothesized that the combined use of PRP and bone marrow-derived mesenchymal stem cells (BMSCs) may repair the early degenerated discs in the long term for their synergistic reparative effect. In the present study, following the induction of early IDD by annular puncture in rabbits, PRP was prepared and mixed with BMSCs (PRP-BMSC group) for injection into the early degenerated discs. As controls, phosphate-buffered saline (PBS; PBS group) and PRP (PRP group) were similarly injected. Rabbits without any intervention served as a control group. At 8 weeks following treatment, histological changes of the injected discs were assessed. Magnetic resonance imaging (MRI) was used to detect the T2-weighted signal intensity of the targeted discs at weeks 1, 2 and 8 following treatment. Annular puncture resulted in disc narrowing and decreased T2-weighted signal intensity. At weeks 1 and 3, MRI examinations showed regenerative changes in the PRP-BMSC group and PRP group, whereas the PBS group exhibited a continuous degenerative process of the discs. At 8 weeks post-injection, the PRP-BMSCs induced a statistically significant restoration of discs, as shown by MRI (PRP-BMSCs, vs.PRP and PBS; P<0.05), which was also confirmed by histological evaluations. Thus, compared with PRP, the administration of PRP-containing BMSCs resulted in a superior regenerative effect on the early degenerated discs, which may be a promising therapeutic strategy for the restoration of early degenerated discs. PMID:26956080

  20. Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.

    PubMed

    Tolonen, Jukka; Grönblad, Mats; Vanharanta, Heikki; Virri, Johanna; Guyer, Richard D; Rytömaa, Tapio; Karaharju, Erkki O

    2006-05-01

    Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus

  1. Comparison of Posterior Lumbar Interbody Fusion and Posterolateral Lumbar Fusion in Monosegmental Vacuum Phenomenon within an Intervertebral Disc

    PubMed Central

    An, Ki-Chan; Kong, Gyu-Min; Park, Dae-Hyun; Youn, Ji-Hong; Lee, Woon-Seong

    2016-01-01

    Study Design Retrospective. Purpose To compare the clinical and radiological outcomes of posterolateral lumbar interbody fusion (PLIF) and posterolateral lumbar fusion (PLF) in monosegmental vacuum phenomenon within an intervertebral disc. Overview of Literature The vacuum phenomenon within an intervertebral disc is a serious form of degenerative disease that destabilizes the intervertebral body. Outcomes of PLIF and PLF in monosegmental vacuum phenomenon are unclear. Methods Monosegmental instrumented PLIF and PLF was performed on 84 degenerative lumbar disease patients with monosegmental vacuum phenomenon (PLIF, n=38; PLF, n=46). Minimum follow-up was 24 months. Clinical outcomes of leg and back pain were assessed using visual analogue scales for leg pain (LVAS) and back pain (BVAS), and the Oswestry disability index (ODI). The radiographic outcome was the estimated bony union rate. Results LVAS, BVAS, and ODI improved in both groups. There was no significant difference in the degree of these improvements between PLIF and PLF patients (p>0.05). Radiological union rate was 91.1% in PLIF group and 89.4% in PLF group at postoperative 24 months (p>0.05). Conclusions No significant differences in clinical results and union rates were found between PLIF and PLF patients. Selection of the operation technique will reflect the surgeon's preferences and patient condition. PMID:26949464

  2. Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model.

    PubMed

    Martin, John T; Milby, Andrew H; Chiaro, Joseph A; Kim, Dong Hwa; Hebela, Nader M; Smith, Lachlan J; Elliott, Dawn M; Mauck, Robert L

    2014-06-01

    Intervertebral disc degeneration has been implicated in the etiology of low back pain; however, the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, can achieve functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilized the motion segment via external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements.

  3. Riboflavin crosslinked high-density collagen gel for the repair of annular defects in intervertebral discs: An in vivo study.

    PubMed

    Grunert, Peter; Borde, Brandon H; Towne, Sara B; Moriguchi, Yu; Hudson, Katherine D; Bonassar, Lawrence J; Härtl, Roger

    2015-10-01

    Open annular defects compromise the ability of the annulus fibrosus to contain nuclear tissue in the disc space, and therefore lead to disc herniation with subsequent degenerative changes to the entire intervertebral disc. This study reports the use of riboflavin crosslinked high-density collagen gel for the repair of annular defects in a needle-punctured rat-tail model. High-density collagen has increased stiffness and greater hydraulic permeability than conventional low-density gels; riboflavin crosslinking further increases these properties. This study found that treating annular defects with crosslinked high-density collagen inhibited the progression of disc degeneration over 18 weeks compared to untreated control discs. Histological sections of FITC-labeled collagen gel revealed an early tight attachment to host annular tissue. The gel was subsequently infiltrated by host fibroblasts which remodeled it into a fibrous cap that bridged the outer disrupted annular fibers and partially repaired the defect. This repair tissue enhanced retention of nucleus pulposus tissue, maintained physiological disc hydration, and preserved hydraulic permeability, according to MRI, histological, and mechanical assessments. Degenerative changes were partially reversed in treated discs, as indicated by an increase in nucleus pulposus size and hydration between weeks 5 and 18. The collagen gel appeared to work as an instant sealant and by enhancing the intrinsic healing capabilities of the host tissue.

  4. Formation of lamellar cross bridges in the annulus fibrosus of the intervertebral disc is a consequence of vascular regression.

    PubMed

    Smith, Lachlan J; Elliott, Dawn M

    2011-05-01

    Cross bridges are radial structures within the highly organized lamellar structure of the annulus fibrosus of the intervertebral disc that connect two or more non-consecutive lamellae. Their origin and function are unknown. During fetal development, blood vessels penetrate deep within the AF and recede during postnatal growth. We hypothesized that cross bridges are the pathways left by these receding blood vessels. Initially, the presence of cross bridges was confirmed in cadaveric human discs aged 25 and 53 years. Next, L1-L2 intervertebral discs (n=4) from sheep ranging in age from 75 days fetal gestation to adult were processed for paraffin histology. Mid-sagittal sections were immunostained for endothelial cell marker PECAM-1. The anterior and posterior AF were imaged using differential interference contrast microscopy, and the following parameters were quantified: total number of distinct lamellae, total number of cross bridges, percentage of cross bridges staining positive for PECAM-1, cross bridge penetration depth (% total lamellae), and PECAM-1 positive cross bridge penetration depth. Cross bridges were first observed at 100 days fetal gestation. The overall number peaked in neonates then remained relatively unchanged. The percentage of PECAM-1 positive cross bridges declined progressively from almost 100% at 100 days gestation to less than 10% in adults. Cross bridge penetration depth peaked in neonates then remained unchanged at subsequent ages. Depth of PECAM-1 positive cross bridges decreased progressively after birth. Findings were similar for both the anterior and posterior. The AF lamellar architecture is established early in development. It later becomes disrupted as a consequence of vascularization. Blood vessels then recede, perhaps due to increasing mechanical stresses in the surrounding matrix. In this study we present evidence that the pathways left by receding blood vessels remain as lamellar cross bridges. It is unclear whether the presence

  5. 1988 Volvo award in basic science. Proteoglycan synthesis in the human intervertebral disc. Variation with age, region and pathology.

    PubMed

    Bayliss, M T; Johnstone, B; O'Brien, J P

    1988-09-01

    Slices of human annulus fibrosus were cultured under conditions that controlled their hydration and prevented loss of proteoglycans from the extracellular matrix. A quantitative analysis of proteoglycan synthesis was carried out. Both the absolute rate of synthesis and the topographical variation in chondrocyte activity changed with age; the most active cells in the adult were found in the mid-annulus region, whereas in the fetal disc the cells in the inner annulus were the most active. The conditions under which the tissue was stored, and changes in hydration during culture, had considerable effects on synthesis. Pathological discs had a wide range of biological activity that reflected the heterogeneous properties of these specimens. It is suggested that this culture method provides a means of investigating the way in which the synthesis of the macromolecular components of the intervertebral disc are coordinated and subsequently incorporated into the extracellular matrix.

  6. Efficacy of Platelet Rich Plasma via Lumbar Epidural Route in Chronic Prolapsed Intervertebral Disc Patients-A Pilot Study

    PubMed Central

    Chopra, Gaurav

    2016-01-01

    Introduction Lumbar radiculopathy is a major health problem often treated by surgery or guided lumbar epidural steroids for pain relief. We have used Platelet Rich Plasma (PRP) a novel therapeutic tool of autologous nature that has emerged strongly in recent years to treat patients of prolapsed intervertebral disc. Aim To evaluate the efficacy of PRP via interlaminar epidural route in treatment of pain in patients with prolapsed inter vertebral disc. Materials and Methods Ten patients were injected with five ml of autologous platelet rich plasma under fluoroscopic guidance via interlaminar lumbar epidural injection into area of affected nerve root. They were followed using VAS (Visual Analogue Scale), SLRT (Straight Leg Raising Test) and MODQ (Modified Oswestry Disability Questionnaire) for clinical improvement. Results Patients who had received epidural injections of autologous PRP showed improvements in their scores of evaluation tools. Improvement was sustained during the 3 month study period and was not associated with any complications. Conclusion Autologous PRP can be considered as a good alternative to epidural steroids and surgery in management of patients with chronic prolapsed intervertebral disc. PMID:27790553

  7. C-Fos Regulation by the MAPK and PKC Pathways in Intervertebral Disc Cells

    PubMed Central

    Yokoyama, Katsuya; Hiyama, Akihiko; Arai, Fumiyuki; Nukaga, Tadashi; Sakai, Daisuke; Mochida, Joji

    2013-01-01

    Background The gene encoding c-fos is an important factor in the pathogenesis of joint disease in patients with osteoarthritis. However, it is unknown whether the signal mechanism of c-fos acts in intervertebral disc (IVD) cells. We investigated whether c-fos is activated in relation to mitogen-activated protein kinases (MAPKs) and the protein kinase C (PKC) pathway in nucleus pulposus (NP) cells. Methodology/Results Reverse transcription-polymerase chain reaction and western blotting analyses were used to measure the expression of c-fos in rat IVD cells. Transfections were performed to determine the effects of c-fos on target gene activity. The effect of c-fos protein expression was examined in transfection experiments and in a 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide cell viability assay. Phorbol 12-myristate 13-acetate (PMA), the most commonly used phorbol ester, binds to and activates protein kinase C (PKC), causing a wide range of effects in cells and tissues. PMA induced the expression of c-fos gene transcription and protein expression, and led to activation of the MAPK pathways in NP cells. The c-fos promoter was suppressed completely in the presence of the MAPK inhibitor PD98059, an inhibitor of the MEK/ERK kinase cascade, but not in the presence of SKF86002, SB202190, or SP600125. The effects of the PKC pathway on the transcriptional activity of the c-fos were evaluated. PKCγ and PKCδ suppressed the promoter activity of c-fos. Treatment with c-fos inhibited aggrecan and Col2 promoter activities and the expression of these genes in NP cells. Conclusions This study demonstrated, for the first time, that the MAPK and PKC pathways had opposing effects on the regulation of c-fos in NP cells. Thus, the expression of c-fos can be suppressed in the extracellular matrix of NP cells. PMID:24023832

  8. Up-regulation of niacinamide in intervertebral disc aggrecan in vitro.

    PubMed

    Xiong, Xiaoqian; Yang, Shuhua; Shao, Zengwu; Liu, Xin; Zhan, Zirui; Duan, Deyu

    2006-01-01

    The regulatory effects of niacinamide (Nia) on intervertebral disc (IVD) aggrecan in vitro was investigated. Chiba's 10 ng/mL interleukin-1 (IL-1)-induced rabbit IVD degeneration model in vitro was established. 0.5, 0.25 and 0.05 mg/mL Nia was added to normal and degenerated IVDs for intervention. On the first and second week after intervention, safranin O-fast green staining intensity and glycosaminoglycan (GS) content were measured. The expression of aggrecan core protein was detected by RT-PCR. The results showed: (1) After treatment with 0.5 mg/mL Nia for one week, the GS content in nucleus pulposus (NP) was increased by 44.8% as compared with control group (P < 0 01); The GS content in IL-1 induction groups was increased with the increase of Nia concentrations: After treatment with 0.5 mg/mL for one week, the GS content in NP was increased by 68.3% as compared with control group (P < 0.01). After two weeks, GS content in NP and fibrous rings was still higher than in control group at the same period (P < 0.01) and untreated group (P < 0.01). (2) Safranin O-fast green staining revealed that with the increase of Nia concentrations, staining density in NP and fibrous rings was increased and histological structure damage to IVDs by IL-1beta was alleviated. (3) RT-PCR showed that the expression of core protein gene in IL-1beta-induced degenerated IVDS was increased with the increase of Nia concentrations. It was concluded that under conditions in vitro, Nia could up-regulate the expression of aggrecan in IVDs and protect IVDs from IL-1beta-induced degeneration at least partially, which offers a potential choice for IVD degeneration clinical therapy.

  9. Coming together is a beginning: the making of an intervertebral disc.

    PubMed

    Chan, Wilson C W; Au, Tiffany Y K; Tam, Vivian; Cheah, Kathryn S E; Chan, Danny

    2014-03-01

    The intervertebral disc (IVD) is a complex fibrocartilaginous structure located between the vertebral bodies that allows for movement and acts as a shock absorber in our spine for daily activities. It is composed of three components: the nucleus pulposus (NP), annulus fibrosus, and cartilaginous endplate. The characteristics of these cells are different, as they produce specific extracellular matrix (ECM) for tissue function and the niche in supporting the differentiation status of the cells in the IVD. Furthermore, cell heterogeneities exist in each compartment. The cells and the supporting ECM change as we age, leading to degenerative outcomes that often lead to pathological symptoms such as back pain and sciatica. There are speculations as to the potential of cell therapy or the use of tissue engineering as treatments. However, the nature of the cells present in the IVD that support tissue function is not clear. This review looks at the origin of cells in the making of an IVD, from the earliest stages of embryogenesis in the formation of the notochord, and its role as a signaling center, guiding the formation of spine, and in its journey to become the NP at the center of the IVD. While our current understanding of the molecular signatures of IVD cells is still limited, the field is moving fast and the potential is enormous as we begin to understand the progenitor and differentiated cells present, their molecular signatures, and signals that we could harness in directing the appropriate in vitro and in vivo cellular responses in our quest to regain or maintain a healthy IVD as we age.

  10. TNFα Transport Induced by Dynamic Loading Alters Biomechanics of Intact Intervertebral Discs

    PubMed Central

    Walter, Benjamin A.; Likhitpanichkul, Morakot; Illien-Junger, Svenja; Roughley, Peter J.; Hecht, Andrew C.; Iatridis, James C.

    2015-01-01

    Objective Intervertebral disc (IVD) degeneration is an important contributor to the development of back pain, and a key factor relating pain and degeneration are the presence of pro-inflammatory cytokines and IVD motion. There is surprisingly limited understanding of how mechanics and inflammation interact in the IVD. This study investigated interactions between mechanical loading and pro-inflammatory cytokines in a large animal organ culture model to address fundamental questions regarding (i.) how inflammatory mediators arise within the IVD, (ii.) how long inflammatory mediators persist, and (iii.) how inflammatory mediators influence IVD biomechanics. Methods Bovine caudal IVDs were cultured for 6 or 20-days under static & dynamic loading with or without exogenous TNFα in the culture medium, simulating a consequence of inflammation of the surrounding spinal tissues. TNFα transport within the IVD was assessed via immunohistochemistry. Changes in IVD structural integrity (dimensions, histology & aggrecan degradation), biomechanical behavior (Creep, Recovery & Dynamic stiffness) and pro-inflammatory cytokines in the culture medium (ELISA) were assessed. Results TNFα was able to penetrate intact IVDs when subjected to dynamic loading but not static loading. Once transported within the IVD, pro-inflammatory mediators persisted for 4–8 days after TNFα removal. TNFα exposure induced changes in IVD biomechanics (reduced diurnal displacements & increased dynamic stiffness). Discussion This study demonstrated that exposure to TNFα, as might occur from injured surrounding tissues, can penetrate healthy intact IVDs, induce expression of additional pro-inflammatory cytokines and alter IVD mechanical behavior. We conclude that exposure to pro-inflammatory cytokine may be an initiating event in the progression of IVD degeneration in addition to being a consequence of disease. PMID:25734788

  11. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.

    PubMed

    Richardson, Stephen M; Kalamegam, Gauthaman; Pushparaj, Peter N; Matta, Csaba; Memic, Adnan; Khademhosseini, Ali; Mobasheri, Reza; Poletti, Fabian L; Hoyland, Judith A; Mobasheri, Ali

    2016-04-15

    Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.

  12. An organ culture system to model early degenerative changes of the intervertebral disc II: profiling global gene expression changes

    PubMed Central

    2013-01-01

    Introduction Despite many advances in our understanding of the molecular basis of disc degeneration, there remains a paucity of preclinical models which can be used to study the biochemical and molecular events that drive disc degeneration, and the effects of potential therapeutic interventions. The goal of this study is to characterize global gene expression changes in a disc organ culture system that mimics early nontraumatic disc degeneration. Methods To mimic a degenerative insult, rat intervertebral discs were cultured in the presence of TNF-α, IL-1β and serum-limiting conditions. Gene expression analysis was performed using a microarray to identify differential gene expression between experimental and control groups. Differential pattern of gene expression was confirmed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or Western blot. Results Treatment resulted in significant changes in expression of more than 1,000 genes affecting many aspects of cell function including cellular movement, the cell cycle, cellular development, and cell death and proliferation. Many of the most highly upregulated and downregulated genes have known functions in disc degeneration and extracellular matrix hemostasis. Construction of gene networks based on known cellular pathways and expression data from our analysis demonstrated that the network associated with cell death, cell cycle regulation and DNA replication and repair was most heavily affected in this model of disc degeneration. Conclusions This rat organ culture model uses cytokine exposure to induce wide gene expression changes with the most affected genes having known reported functions in disc degeneration. We propose that this model is a valuable tool to study the etiology of disc degeneration and evaluate potential therapeutic treatments. PMID:24171898

  13. Regression of anterior disc-osteophyte complex following cervical laminectomy and fusion for cervical spondylotic myelopathy

    PubMed Central

    Ashana, Adedayo O.; Cohen, Jeremiah R.; Evans, Brandon; Holly, Langston T.

    2014-01-01

    Study Design Retrospective case control study Objective To investigate whether posterior cervical laminectomy and fusion modifies the natural course of anterior disc-osteophyte complex in patients with multilevel CSM Summary of Background Data Dorsal migration of the spinal cord is the main purported mechanism of spinal cord decompression following cervical laminectomy and fusion but other potential mechanisms have received scant attention in the literature. This study was conducted to investigate whether cervical laminectomy and fusion affects the size of anterior disc osteophyte complex. Methods The medical records and radiographical imaging of 44 patients that underwent cervical laminectomy and fusion for CSM between 2006 and 2013 were analyzed. The size of the anterior disc osteophyte complex was measured pre and postoperatively on MR images taken at an interval of > 3 months apart. A control group consisted of 20 non-operatively treated advanced cervical spondylosis patients. Patients in the control met the same inclusion and exclusion criteria and also had sequential MRI taken at an interval of > 3 months apart. Results The nonoperative and operative groups were statistically similar in the pertinent patient demographics and characteristics including gender, age, time to second MRI, size of anterior disc-osteophyte complex on baseline MRI, mean number of levels affected, and percentage of patients with T2 signal change. As expected the mJOA scores were significantly lower in the operative versus nonoperative cohort (13.6 vs. 16.5, P<0.01). A significant decrease in the size of anterior disc osteophyte was observed in the operative group postoperatively (P<0.01). In comparison, there was no statistically significant change in the size of the anterior disc osteophyte complex in the control group (P > 0.05). The magnitude of the change in disc size between the two groups was statistically significant (P <0.01). Conclusion The findings of this study suggest that

  14. [The synergistic effect of amygdalin and HSYA on the IL-1beta induced endplate chondrocytes of rat intervertebral discs].

    PubMed

    Niu, Kai; Zhao, Yong-Jian; Zhang, Lei; Li, Chen-Guang; Wang, Yong-Jun; Zheng, Wei-Chao

    2014-08-01

    The effect of amygdalin joint hydroxysafflor yellow A (HSYA) on the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and the possible mechanism were studied and explored. Chondrocytes were obtained from endplate of one-month SD rat intervertebral discs and cultured primary endplate chondrocytes. After identification, they were divided into normal group, induced group, amygdalin group, HSYA group and combined group. CCK-8 kit was adopted to detect the proliferation of the endplate chondrocytes. FCM was measured to detect the apoptosis. Real-time PCR method was adopted to observe the mRNA expression of Aggrecan, Col 2 alpha1, Col 10 alpha1, MMP-13 and the inflammatory cytokines IL-1beta. The protein expression of Col II, Col X was tested through immunofluorescence. Compared with the normal group, the proliferation of the endplate chondrocytes decreased while the apoptosis increased (P < 0.05). With down regulation of the mRNA expressions of Aggrecan, Col 2 alpha1 and up regulation of the mRNA expressions of Col 10 alpha1, MMP-13, IL-1beta (P < 0.05), the protein expression of Col II decreased while the protein expression of Col X increased. Compared with the induced group, amygdalin group, HSYA group, the combined group could inhibit the apoptosis and promote the proliferation (P < 0.05). They could increase the mRNA expressions of Aggrecan and Col 2 alpha1 while decrease the mRNA expressions of Col 10 alpha1, MMP-13 and IL-1beta (P < 0.05). They could also enhance the protein expression of Col II while reduce the protein expression of Col X. The effect of the combined group was significantly better than that of amygdalin and HSYA. Amygdalin joint HSYA could inhibit the degeneration of the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and better than the single use of amygdalin or HSYA.

  15. Form and function of the intervertebral disc in health and disease: a morphological and stain comparison study

    PubMed Central

    Walter, B. A.; Torre, O. M.; Laudier, D.; Naidich, T. P.; Hecht, A. C.; Iatridis, J. C.

    2015-01-01

    Multiple histologic measurements are commonly used to assess degenerative changes in intervertebral disc (IVD) structure; however, there is no consensus on which stains offer the clearest visualization of specific areas within the IVD. The objective of this study was to compare multiple tinctorial stains, evaluate their ability to highlight structural features within the IVD, and investigate how they influence the capacity to implement a degeneration scoring system. Lumbar IVDs from seven human autopsy specimens were stained using six commonly used stains (Hematoxylin/Eosin, Toluidine Blue, Safranin-O/Fast Green, Extended FAST, modified Gomori’s Trichrome, and Picrosirius Red Alcian Blue). All IVDs were evaluated by three separate graders to independently determine which stains (i) were most effective at discerning different structural features within different regions of the IVDs and (ii) allowed for the most reproducible assessment of degeneration grade, as assessed via the Rutges histological scoring system (Rutges et al. A validated new histological classification for intervertebral disc degeneration. Osteoarthritis Cartilage, 21, 2039-47). Although Trichrome, XFAST and PR/AB stains were all effective at highlighting different regions of whole IVDs, we recommend the use of PR/AB because it had the highest degree of rater agreement on assigned degeneration grade, allowed greater resolution of degeneration grade, has an inferential relationship between color and composition, and allowed clear differentiation of the different regions and structural disruptions within the IVD. The use of a standard set of stains together with a histological grading scheme can aid in the characterization of structural changes in different regions of the IVD and may simplify comparisons across the field. This collection of human IVD histological images highlights how IVD degeneration is not a single disease but a composite of multiple processes such as aging, injury, repair, and

  16. Changes in nuclear composition following cyclic compression of the intervertebral disc in an in vivo rat-tail model.

    PubMed

    Ching, Congo T S; Chow, Daniel H K; Yao, Fiona Y D; Holmes, Andrew D

    2004-09-01

    While in vitro studies have shown that mechanical loading can result in changes in the composition of intervertebral disc matrix, the effects of cyclic loading in vivo have not been considered. The objective of this study was to assess the effect of static and cyclic compression of different frequencies on the nuclear composition of the intervertebral disc. Thirty-six Sprague-Dawley rats were randomly divided into a control group (no pin insertion, no loading), a sham group (pins inserted in sixth and seventh caudal vertebrae, no loading), a static loading group (compression applied via pins) and cyclic loading groups (loading at 0.5, 1.5 or 2.5 Hz). Loading was applied for 1 h each day from the third to 17th day following pin insertion, and the caudal 5-6, 6-7 and 7-8 discs harvested to quantify proteoglycan content, collagen content and chondrocyte density in the nucleus pulposus. Static compression resulted in a significant reduction in total proteoglycan content as compared with the adjacent control disc, but this effect was not seen in any of the cyclic loading groups. However, comparison with the sham group appears to indicate an overall decrease in total proteoglycan content at the targeted and adjacent levels following cyclic loading. The 0.5 Hz loading group showed a significantly greater total proteoglycan content than all other compression groups, and also showed a lower total collagen content than the sham group. Results suggest that frequency dependent changes in composition occur in response to cyclic loading, but are not limited to the directly loaded disc alone. Further studies are required to verify this, but the choice of control appears to need careful consideration in all studies of this nature.

  17. Double and zero quantum filtered 2H NMR analysis of D2O in intervertebral disc tissue

    NASA Astrophysics Data System (ADS)

    Ooms, Kristopher J.; Vega, Alexander J.; Polenova, Tatyana; Cannella, Marco; Marcolongo, Michele

    2015-09-01

    The analysis of double and zero quantum filtered 2H NMR spectra obtained from D2O perfused in the nucleus pulposus of human intervertebral disc tissue samples is reported. Fitting the spectra with a three-site model allows for residual quadrupolar couplings and T2 relaxation times to be measured. The analysis reveals changes in both the couplings and relaxation times as the tissue begins to show signs of degradation. The full analysis demonstrates that information about tissue hydration, water collagen interactions, and sample heterogeneity can be obtained and used to better understand the biochemical differences between healthy and degraded tissue.

  18. Imbalanced Protein Expression Patterns of Anabolic, Catabolic, Anti-Catabolic and Inflammatory Cytokines in Degenerative Cervical Disc Cells: New Indications for Gene Therapeutic Treatments of Cervical Disc Diseases

    PubMed Central

    Mern, Demissew S.; Beierfuß, Anja; Fontana, Johann; Thomé, Claudius; Hegewald, Aldemar A.

    2014-01-01

    Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix

  19. 3D finite element analysis of nutrient distributions and cell viability in the intervertebral disc: effects of deformation and degeneration.

    PubMed

    Jackson, Alicia R; Huang, Chun-Yuh C; Brown, Mark D; Gu, Wei Yong

    2011-09-01

    The intervertebral disc (IVD) receives important nutrients, such as glucose, from surrounding blood vessels. Poor nutritional supply is believed to play a key role in disc degeneration. Several investigators have presented finite element models of the IVD to investigate disc nutrition; however, none has predicted nutrient levels and cell viability in the disc with a realistic 3D geometry and tissue properties coupled to mechanical deformation. Understanding how degeneration and loading affect nutrition and cell viability is necessary for elucidating the mechanisms of disc degeneration and low back pain. The objective of this study was to analyze the effects of disc degeneration and static deformation on glucose distributions and cell viability in the IVD using finite element analysis. A realistic 3D finite element model of the IVD was developed based on mechano-electrochemical mixture theory. In the model, the cellular metabolic activities and viability were related to nutrient concentrations, and transport properties of nutrients were dependent on tissue deformation. The effects of disc degeneration and mechanical compression on glucose concentrations and cell density distributions in the IVD were investigated. To examine effects of disc degeneration, tissue properties were altered to reflect those of degenerated tissue, including reduced water content, fixed charge density, height, and endplate permeability. Two mechanical loading conditions were also investigated: a reference (undeformed) case and a 10% static deformation case. In general, nutrient levels decreased moving away from the nutritional supply at the disc periphery. Minimum glucose levels were at the interface between the nucleus and annulus regions of the disc. Deformation caused a 6.2% decrease in the minimum glucose concentration in the normal IVD, while degeneration resulted in an 80% decrease. Although cell density was not affected in the undeformed normal disc, there was a decrease in cell

  20. Durability of cervical disc arthroplasties and its influence factors

    PubMed Central

    Chen, Chao; Zhang, Xiaolin; Ma, Xinlong

    2017-01-01

    Abstract Background: The durability of cervical disc arthroplasties (CDA) may vary significantly because of different designs and implanting techniques of the devices. Nevertheless, the comparative durability remains unknown. Objectives: We aimed to assess the durability of CDAs in at least 2-year follow-up. We analyzed the classifications and causes of secondary surgical procedures, as well as the structural designs of the devices that might influence the durability. Methods: PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials were searched from the inception of each database to September 2015 using the following Keywords: “cervical disc replacement” OR “cervical disc arthroplasty” AND “randomized controlled trial (RCT).” Publication language was restricted to English. The primary outcome was the rate of secondary surgical procedures following CDA or anterior cervical decompression and fusion (ACDF). Pairwise meta-analysis and a Bayesian network meta-analysis were carried out using Review Manager v5.3.5 and WinBUGS version 1.4.3, respectively. Quality of evidence was appraised by Grading of Recommendations Assessment, Development and Evaluation methodology. Results: Twelve RCTs that met the eligibility criteria were included. Follow-up ranged from 2 years to 7 years. A total of 103 secondary surgical procedures were performed. The most frequent classification of secondary surgical procedures was reoperation (48/103) and removal (47/103). Revision (3/103) and supplementary fixation (2/103) were rare. Adjacent-level diseases were the most common cause of reoperations. The rates of secondary surgical procedures were significantly lower in Mobi-C, Prestige, Prodisc-C, Secure-C group than in ACDF group. No significant difference was detected between Bryan, PCM, Kineflex-C, Discover, and ACDF. Mobi-C, Secure-C, and Prodisc-C ranked the best, the second best, the third best, respectively. Conclusions: We concluded that Mobi-C, Secure

  1. Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity

    PubMed Central

    Jia, Haobo; Ma, Jianxiong; Lv, Jianwei; Ma, Xinlong; Xu, Weiguo; Yang, Yang; Tian, Aixian; Wang, Ying; Sun, Lei; Xu, Liyan; Fu, Lin; Zhao, Jie

    2016-01-01

    To investigate the mitigation effect and mechanism of oestrogen and PTH on disc degeneration in rats after ovariectomy, as well as on Wnt/β-catenin pathway activity, thirty 3-month-old rats were ovariectomized and divided into three groups. Ten additional rats were used as controls. Eight weeks later, the rats were administered oestrogen or PTH for 12 weeks, and then discs were collected for tests. Results showed that nucleus pulposus cells in the Sham group were mostly notochord cells, while in the OVX group, cells gradually developed into chondrocyte-like cells. Oestrogen or PTH could partly recover the notochord cell number. After ovariectomy, the endplate roughened and endplate porosity decreased. After oestrogen or PTH treatment, the smoothness and porosity of endplate recovered. Compared with the Sham group, Aggrecan, Col2a and Wnt/β-catenin pathway expression in OVX group decreased, and either oestrogen or PTH treatment improved their expression. The biomechanical properties of intervertebral disc significantly changed after ovariectomy, and oestrogen or PTH treatment partly recovered them. Disc degeneration occurred with low oestrogen, and the underlying mechanisms involve nutrition supply disorders, cell type changes and decreased Wnt/β-catenin pathway activity. Oestrogen and PTH can retard disc degeneration in OVX rats and enhance Wnt/β-catenin pathway activity in nucleus pulposus. PMID:27279629

  2. Regional annulus fibre orientations used as a tool for the calibration of lumbar intervertebral disc finite element models.

    PubMed

    Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien

    2013-01-01

    The collagen network of the annulus fibrosus largely controls the functional biomechanics of the lumbar intervertebral discs (IVDs). Quantitative anatomical examinations have shown bundle orientation patterns, possibly coming from regional adaptations of the annulus mechanics. This study aimed to show that the regional differences in annulus mechanical behaviour could be reproduced by considering only fibre orientation changes. Using the finite element method, a lumbar annulus was modelled as a poro-hyperelastic material in which fibres were represented by a direction-dependent strain energy density term. Fibre orientations were calibrated to reproduce the annulus tensile behaviours measured for four different regions: posterior outer, anterior outer, posterior inner and anterior inner. The back-calculated fibre angles and regional patterns as well as the global disc behaviour were comparable with anatomical descriptions reported in the literature. It was concluded that annulus fibre variations might be an effective tool to calibrate lumbar spine IVD and segment models.

  3. Strain distribution in the intervertebral disc under unconfined compression and tension load by the optimized digital image correlation technique.

    PubMed

    Liu, Qing; Wang, Tai-Yong; Yang, Xiu-Ping; Li, Kun; Gao, Li-Lan; Zhang, Chun-Qiu; Guo, Yue-Hong

    2014-05-01

    The unconfined compression and tension experiments of the intervertebral disc were conducted by applying an optimized digital image correlation technique, and the internal strain distribution was analysed for the disc. It was found that the axial strain values of different positions increased obviously with the increase in loads, while inner annulus fibrosus and posterior annulus fibrosus experienced higher axial strains than the outer annulus fibrosus and anterior annulus fibrosus. Deep annulus fibrosus exhibited higher compressive and tensile axial strains than superficial annulus fibrosus for the anterior region, while there was an opposite result for the posterior region. It was noted that all samples demonstrated a nonlinear stress-strain profile in the process of deforming, and an elastic region was shown once the sample was deformed beyond its toe region.

  4. 1991 Volvo Award in basic sciences. Collagen types around the cells of the intervertebral disc and cartilage end plate: an immunolocalization study.

    PubMed

    Roberts, S; Menage, J; Duance, V; Wotton, S; Ayad, S

    1991-09-01

    Several types of collagen are known to exist in the intervertebral disc in addition to the fibrillar collagens, Types I and II. Although they constitute only a small percentage of the total collagen content, these minor collagens may have important functions. This study was designed to investigate the presence of Types I, II, III, IV, VI, and IX collagens in the intervertebral disc and cartilage end plate by immunohistochemistry, thereby establishing their location within the tissues. Types III and VI collagen have a pericellular distribution in animal and human tissue. No staining for Type IX collagen was present in normal human disc, but in rat and bovine intervertebral disc, it was also located pericellularly. These results show that cells of the intervertebral disc and cartilage end plate sit in fibrous capsules, forming chondrons similar to those described in articular cartilage. In pathologic tissue the amount and distribution of the collagen types, and the organization of the pericellular capsule, differ from that seen in control material.

  5. MRI analysis of the ISOBAR TTL internal fixation system for the dynamic fixation of intervertebral discs: a comparison with rigid internal fixation

    PubMed Central

    2014-01-01

    Objectives Using magnetic resonance imaging (MRI), we analyzed the efficacy of the posterior approach lumbar ISOBAR TTL internal fixation system for the dynamic fixation of intervertebral discs, with particular emphasis on its effects on degenerative intervertebral disc disease. Methods We retrospectively compared the MRIs of 54 patients who had previously undergone either rigid internal fixation of the lumbar spine or ISOBAR TTL dynamic fixation for the treatment of lumbar spondylolisthesis. All patients had received preoperative and 6-, 12-, and 24-month postoperative MRI scans of the lumbar spine with acquisition of both routine and diffusion-weighted images (DWI). The upper-segment discs of the fusion were subjected to Pfirrmann grading, and the lumbar intervertebral discs in the DWI sagittal plane were manually drawn; the apparent diffusion coefficient (ADC) value was measured. Results ADC values in the ISOBAR TTL dynamic fixation group measured at the 6-, 12-, and 24-month postoperative MRI studies were increased compared to the preoperative ADC values. The ADC values in the ISOBAR TTL dynamic fixation group at 24 months postoperatively were significantly different from the preoperative values (P < 0.05). At 24 months, the postoperative ADC values were significantly different between the rigid fixation group and the ISOBAR TTL dynamic fixation group (P < 0.05). Conclusion MRI imaging findings indicated that the posterior approach lumbar ISOBAR TTL internal fixation system can prevent or delay the degeneration of intervertebral discs. PMID:24898377

  6. Hydrogen sulfide protects against endoplasmic reticulum stress and mitochondrial injury in nucleus pulposus cells and ameliorates intervertebral disc degeneration.

    PubMed

    Xu, Daoliang; Jin, Haiming; Wen, Jianxia; Chen, Jiaoxiang; Chen, Deheng; Cai, Ningyu; Wang, Yongli; Wang, Jianle; Chen, Yu; Zhang, Xiaolei; Wang, Xiangyang

    2017-03-01

    It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)-1β, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL-1β-induced apoptosis in nucleus pulposus (NP) cells. Here, we found that the expression levels of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), two key enzymes in the generation of H2S, were significantly decreased in human degenerate NP tissues as well as in IL-1β-treated NP cells. NaHS (H2S donor) administration showed a protective effect by inhibiting the endoplasmic reticulum (ER) stress response and mitochondrial dysfunction induced by IL-1β stimulation in vitro, the effect was related to activation of the PI3K/Akt and ERK1/2 signaling pathways. Suppression of these pathways by specific inhibitors, LY294002 and PD98059, partially reduced the protective effect of NaHS. Moreover, in the percutaneous needle puncture disc degeneration rat tail model, disc degeneration was partially reversed by NaHS administration. Taken together, our results suggest that H2S plays a protective role in IVDD and the underlying mechanism involves PI3K/Akt and ERK1/2 signaling pathways-mediated suppression of ER stress and mitochondrial dysfunction in IL-1β-induced NP cells.

  7. Cervical disc herniation as a trigger for temporary cervical cord ischemia

    PubMed Central

    Acker, Güliz; Schneider, Ulf C.; Grozdanovic, Zarko; Vajkoczy, Peter

    2016-01-01

    Background Disc herniations are only reported in few case reports as a rare cause of acute spinal ischemia. A surgical treatment has not been described so far in these reports with analysis of diffusion weighted magnetic resonance imaging (DWI/MRI) before and after surgery. The aim of our study is to report a case of cervical spinal cord ischemia caused by cervical disc herniation and discuss the literature concerning diagnostic and treatment options. Methods A 72-year-old female patient developed an acute progressive tetraparesis with emphasis on the upper extremities. MRI showed a disc herniation at the cervical segment 5/6 (C5/6) with consecutive spinal canal stenosis and additional signs of spinal cord ischemia in T2-weighted imaging (T2WI) and DWI reaching from C3 to C5 level. With the MRI being highly suggestive for anterior spinal cord ischemia, we hypothesized that this might be caused by compression of the anterior spinal artery through the significant disc herniation. Therefore, we decided to perform an anterior discectomy and fusion at C5/6 level. Results Following surgery, the patient’s symptoms showed immediate regression with complete recovery after two months in correspondence with the normalization in the control MRI scan of cervical cord. Conclusions Assumedly our patient suffered from a partial anterior spinal artery syndrome, possibly caused by a disc herniation-related compression that was reversible following surgery. This was accompanied by a complete resolution of spinal cord signal abnormalities in T2WI and DWI. PMID:27683710

  8. Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc

    PubMed Central

    Yu, Fei; Ma, Junxuan

    2017-01-01

    Low back pain (LBP) is the leading cause of disability in the elderly. Intervertebral disc degeneration (IDD) was considered as the main cause for LBP. Degeneration of cartilaginous endplate was a crucial harmful factor during the initiation and development of IDD. Oxidative stress was implicated in IDD. However, the underlying molecular mechanism for the degeneration of cartilaginous endplate remains elusive. Herein, we found that oxidative stress could induce apoptosis and autophagy in endplate chondrocytes evidenced by western blot analysis, flow cytometry, immunofluorescence staining, GFP-LC3B transfection, and MDC staining. In addition, we also found that the apoptosis of endplate chondrocytes was significantly increased after the inhibition of autophagy by bafilomycin A1 shown by flow cytometry. Furthermore, mTOR pathway upstream autophagy was greatly suppressed suggested by western blot assay. In conclusion, our study strongly revealed that oxidative stress could increase autophagy and apoptosis of endplate chondrocytes in intervertebral disc. The increase of autophagy activity could prevent endplate chondrocytes from apoptosis. The autophagy in endplate chondrocytes induced by oxidative stress was mTOR dependent. These findings might shed some new lights on the mechanism for IDD and provide new strategies for the treatments of IDD. PMID:28321270

  9. Surgical technique for revision surgery of cervical artificial disc replacements.

    PubMed

    Onken, Julia; Meyer, Bernhard; Vajkoczy, Peter

    2017-01-01

    OBJECTIVE Cervical artificial disc replacement (C-ADR) is a widely used procedure with low risk at implantation. Few cases have been reported about the surgical techniques of C-ADR revision. The authors describe their surgical experience with the explantation of a Galileo C-ADR. METHODS Revision surgery was performed in a 58-year-old patient. Patient positioning and surgical opening techniques were performed as appropriate for anterior cervical decompression. RESULTS Revision surgery via the initial anterior approach was successful following an atraumatic removal of the implant. Fusion of the C5-6 segment was performed without complications. CONCLUSIONS In general, the authors observed recurrent nerve palsy and malpositioning of the revised implant in C-ADR revision surgery. Problems with implant removal did not occur because the fusion rate was low due to the short time between initial surgery and C-ADR revision surgery. The video can be found here: https://youtu.be/32CUEDquinc .

  10. MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration

    PubMed Central

    Qin, Chuqiang; Zhang, Bo; Zhang, Liang; Zhang, Zhi; Wang, Le; Tang, Long; Li, Shuangqing; Yang, Yixi; Yang, Fuguo; Zhang, Ping; Yang, Bo

    2016-01-01

    Lower back pain (LBP) is a common and remitting problem. One of the primary causes of LBP is thought to be degeneration of the intervertebral disc (IVD). The aim of the present study was to investigate the role of the myeloid differentiation primary-response protein 88 (MyD88)-dependent Toll-like receptor 4 (TLR4) signal pathway in the mechanism of IVD degeneration. IVD nucleus pulposus cells isolated and cultured from the lumbar vertebrae of Wistar rats were stimulated by various doses of lipopolysaccharide (LPS; 0.1, 1, 10 and 100 µg/ml) to simulate IVD degeneration. Cells were rinsed and cultured in serum-free Dulbecco's modified Eagle's medium/F12. Reverse transcription-quantitative polymerase chain reaction was used to determine the levels of TLR4, MyD88, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β) mRNA expression after 1, 3, 6, 9 and 12 h of incubation. Additionally, western blot and enzyme-linked immunosorbent assay analyses were used to determine the levels of TLR4, MyD88, TNFα, and IL-1β protein expression after 24, 48 and 72 h of incubation. The levels of TLR4, MyD88, TNFα and IL-1β mRNA all increased in the cells stimulated by 10 µg/ml LPS at 3, 6 and 9 h (all P<0.001). Furthermore, the levels of TLR4, MyD88, TNFα and IL-1β protein all increased at 24, 48 and 72 h (all P<0.001). Additionally, the mRNA and protein levels of TLR4, MyD88, TNFα and IL-1β increased significantly in the cells stimulated by 1, 10 and 100 µg/ml LPS compared with the control group, and reached a peak in the 10 µg/ml LPS group (all P<0.001). These results suggest that the MyD88-dependent TLR4 signal pathway is a target pathway in IVD degeneration. This pathway is time phase- and dose-dependent, and when activated can lead to the release of inflammatory factors that participate in IVD degeneration. PMID:27446251

  11. Calibration of hyperelastic material properties of the human lumbar intervertebral disc under fast dynamic compressive loads.

    PubMed

    Wagnac, Eric; Arnoux, Pierre-Jean; Garo, Anaïs; El-Rich, Marwan; Aubin, Carl-Eric

    2011-10-01

    Under fast dynamic loading conditions (e.g. high-energy impact), the load rate dependency of the intervertebral disc (IVD) material properties may play a crucial role in the biomechanics of spinal trauma. However, most finite element models (FEM) of dynamic spinal trauma uses material properties derived from quasi-static experiments, thus neglecting this load rate dependency. The aim of this study was to identify hyperelastic material properties that ensure a more biofidelic simulation of the IVD under a fast dynamic compressive load. A hyperelastic material law based on a first-order Mooney-Rivlin formulation was implemented in a detailed FEM of a L2-L3 functional spinal unit (FSU) to represent the mechanical behavior of the IVD. Bony structures were modeled using an elasto-plastic Johnson-Cook material law that simulates bone fracture while ligaments were governed by a viscoelastic material law. To mimic experimental studies performed in fast dynamic compression, a compressive loading velocity of 1 m/s was applied to the superior half of L2, while the inferior half of L3 was fixed. An exploratory technique was used to simulate dynamic compression of the FSU using 34 sets of hyperelastic material constants randomly selected using an optimal Latin hypercube algorithm and a set of material constants derived from quasi-static experiments. Selection or rejection of the sets of material constants was based on compressive stiffness and failure parameters criteria measured experimentally. The two simulations performed with calibrated hyperelastic constants resulted in nonlinear load-displacement curves with compressive stiffness (7335 and 7079 N/mm), load (12,488 and 12,473 N), displacement (1.95 and 2.09 mm) and energy at failure (13.5 and 14.7 J) in agreement with experimental results (6551 ± 2017 N/mm, 12,411 ± 829 N, 2.1 ± 0.2 mm and 13.0 ± 1.5 J respectively). The fracture pattern and location also agreed with experimental results. The simulation performed with

  12. Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study

    PubMed Central

    Capoor, Manu N.; Ruzicka, Filip; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Schmitz, Jonathan E.; Hermanova, Marketa; Sana, Jiri; Michu, Elleni; Baird, John C.; Ahmed, Fahad S.; Maca, Karel; Lipina, Radim; Alamin, Todd F.; Coscia, Michael F.; Stonemetz, Jerry L.; Witham, Timothy; Ehrlich, Garth D.; Gokaslan, Ziya L.; Mavrommatis, Konstantinos; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej

    2016-01-01

    Background The relationship between intervertebral disc degeneration and chronic infection by Propionibacterium acnes is controversial with contradictory evidence available in the literature. Previous studies investigating these relationships were under-powered and fraught with methodical differences; moreover, they have not taken into consideration P. acnes’ ability to form biofilms or attempted to quantitate the bioburden with regard to determining bacterial counts/genome equivalents as criteria to differentiate true infection from contamination. The aim of this prospective cross-sectional study was to determine the prevalence of P. acnes in patients undergoing lumbar disc microdiscectomy. Methods and Findings The sample consisted of 290 adult patients undergoing lumbar microdiscectomy for symptomatic lumbar disc herniation. An intraoperative biopsy and pre-operative clinical data were taken in all cases. One biopsy fragment was homogenized and used for quantitative anaerobic culture and a second was frozen and used for real-time PCR-based quantification of P. acnes genomes. P. acnes was identified in 115 cases (40%), coagulase-negative staphylococci in 31 cases (11%) and alpha-hemolytic streptococci in 8 cases (3%). P. acnes counts ranged from 100 to 9000 CFU/ml with a median of 400 CFU/ml. The prevalence of intervertebral discs with abundant P. acnes (≥ 1x103 CFU/ml) was 11% (39 cases). There was significant correlation between the bacterial counts obtained by culture and the number of P. acnes genomes detected by real-time PCR (r = 0.4363, p<0.0001). Conclusions In a large series of patients, the prevalence of discs with abundant P. acnes was 11%. We believe, disc tissue homogenization releases P. acnes from the biofilm so that they can then potentially be cultured, reducing the rate of false-negative cultures. Further, quantification study revealing significant bioburden based on both culture and real-time PCR minimize the likelihood that observed

  13. A Meta-Analysis Comparing the Results of Cervical Disc Arthroplasty with Anterior Cervical Discectomy and Fusion (ACDF) for the Treatment of Symptomatic Cervical Disc Disease

    PubMed Central

    Gao, Yu; Liu, Ming; Li, Tao; Huang, Fuguo; Tang, Tingting; Xiang, Zhou

    2013-01-01

    Background: Anterior cervical discectomy and fusion is a standard treatment for symptomatic cervical disc disease, but pseudarthrosis and accelerated adjacent-level disc degeneration may develop. Cervical disc arthroplasty was developed to preserve the kinematics of the functional spinal unit. Trials comparing arthroplasty with anterior cervical discectomy and fusion have shown unclear benefits in terms of clinical results, neck motion at the operated level, adverse events, and the need for secondary surgical procedures. Methods: Only randomized clinical trials were included in this meta-analysis, and the search strategy followed the requirements of the Cochrane Library Handbook. Two reviewers independently assessed the methodological quality of each included study and extracted the relevant data. Results: Twenty-seven randomized clinical trials were included; twelve studies were Level I and fifteen were Level II. The results of the meta-analysis indicated longer operative times, more blood loss, lower neck and arm pain scores reported on a visual analog scale, better neurological success, greater motion at the operated level, fewer secondary surgical procedures, and fewer such procedures that involved supplemental fixation or revision in the arthroplasty group compared with the anterior cervical discectomy and fusion group. These differences were significant (p < 0.05). The two groups had similar lengths of hospital stay, Neck Disability Index scores, and rates of adverse events, removals, and reoperations (p > 0.05). Conclusions: The meta-analysis revealed that anterior cervical discectomy and fusion was associated with shorter operative times and less blood loss compared with arthroplasty. Other outcomes after arthroplasty (length of hospital stay, clinical indices, range of motion at the operated level, adverse events, and secondary surgical procedures) were superior or equivalent to the outcomes after anterior cervical discectomy and fusion. Level of Evidence

  14. Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege Reinforcement by Fas/FasL Regulating Machinery.

    PubMed

    Ma, Chi-Jiao; Liu, Xu; Che, Lu; Liu, Zhi-Heng; Samartzis, Dino; Wang, Hai-Qiang

    2015-01-01

    As a main contributing factor to low back pain, intervertebral disc degeneration (IDD) is the fundamental basis for various debilitating spinal diseases. The pros and cons of current treatment modalities necessitate biological treatment strategies targeting for reversing or altering the degeneration process in terms of molecules or genes. The advances in stem cell research facilitate the studies aiming for possible clinical application of stem cell therapies for IDD. Human NP cells are versatile with cell morphology full of variety, capable of synthesizing extracellular matrix components, engulfing substances by autophagy and phagocytosis, mitochondrial vacuolization indicating dysfunction, expressing Fas and FasL as significant omens of immune privileged sites. Human discs belong to immune privilege organs with functional FasL expression, which can interact with invasive immune cells by Fas-FasL regulatory machinery. IDD is characterized by decreased expression level of FasL with dysfunctional FasL, which in turn unbalances the interaction between NP cells and immune cells. Certain modulation factors might play a role in the process, such as miR-155. Accumulating evidence indicates that Fas-FasL network expresses in a variety of stem cells. Given the expression of functional FasL and insensitive Fas in stem cells (we term as FasL privilege), transplantation of stem cells into the disc may regenerate the degenerative disc by not only differentiating into NP-like cells, increasing extracellular matrix, but also reinforce immune privilege via interaction with immune cells by Fas-FasL network.

  15. Clinical and radiologic comparison of dynamic cervical implant arthroplasty and cervical total disc replacement for single-level cervical degenerative disc disease.

    PubMed

    Shichang, Liu; Yueming, Song; Limin, Liu; Lei, Wang; Zhongjie, Zhou; Chunguang, Zhou; Xi, Yang

    2016-05-01

    Anterior cervical discectomy and fusion, to date the most successful spine procedure for the surgical treatment of cervical radiculopathy, has limitations that have led to the development of non-fusion cervical procedures, such as cervical total disc replacement (TDR) and dynamic cervical implant (DCI) arthroplasty. We compared the clinical and radiological results of DCI and cervical TDR for the treatment of single-level cervical degenerative disc disease in Chinese patients. A retrospective review of 179 patients with cervical spondylotic myelopathy who underwent DCI or TDR between April 2010 and October 2012 was conducted, and 152 consecutive patients (67 patients single-level DCI and 85 single-level TDR) who completed at least 2years of follow-up were included. Clinical and radiological assessments were performed preoperatively and at 1week and 3, 6, 12, and 24months postoperatively. The most common operative level was C5/C6 (49.3%). The differences in blood loss, duration of surgery, and duration of hospitalization were not statistically significant. The Japanese Orthopaedic Association scale, Visual Analog Scale, Neck Disability Index, and Short Form-36 scores improved significantly after surgery in both the DCI and TDR groups (P<0.05), but the differences were not statistically significant at the final follow-up. The rate of occurrence of heterotopic ossification was 22.4% and 28.2% in the DCI and TDR groups, respectively. As an effective non-fusion technique, DCI is a more economical procedure. Further prospective, randomized studies with long-term follow-up periods are needed to determine the long-term effects.

  16. Menopause causes vertebral endplate degeneration and decrease in nutrient diffusion to the intervertebral discs.

    PubMed

    Wang, Yi-Xiang J; Griffith, James F

    2011-07-01

    The vasculature in the outer annulus supplies only the periphery of the disc so that nutrition to the bulk of the disc, including all the inner annulus and nucleus pulposus, is derived from the vertebral epiphyseal end arteries where nutrients diffuse across the cartilaginous endplate to reach the disc. In this regard the vertebral endplate plays an important role in disc nutrition. Compromise of diffusion of nutrients to the disc cells may play a large part in the progression or even initiation of disc degeneration. Increasing evidence suggests that estrogen deficiency also influence the severity of disc degeneration in post-menopausal females. Structural disorganization of the vertebral endplate occurs with disc degeneration, with the most common endplate changes observed clinically being Schmorl's node. Schmorl's node is more commonly seen in post-menopausal women than younger women. Osteosclerosis, osteonecrosis and fibrosis associated with Schmorl's nodes can impede nutrient diffusion into the disc as well as removal of metabolites from the disc. We hypothesize that menopause negatively affects vertebral endplate quality and induces endplate degeneration. This endplate degeneration decreases nutrients diffusion from vertebral body into discs, and also impedes removal of metabolites, leads to further disc degeneration. To confirm our hypothesis, a cross-sectional post-contrast MRI study can be performed in pre-menopausal and post-menopausal women. If the hypothesis is confirmed, then low dose hormone replacement treatment may retard disc degeneration in post menopausal women and thereby limit the consequences associated with disc degeneration such as low back pain.

  17. Deuk Laser Disc Repair® is a safe and effective treatment for symptomatic cervical disc disease

    PubMed Central

    Deukmedjian, Ara J.; Jason Cutright, S. T.; Augusto Cianciabella, PA-C; Deukmedjian, Arias

    2013-01-01

    Background: Deuk Laser Disc Repair® is a new full-endoscopic surgical procedure to repair symptomatic cervical disc disease. Methods: A prospective cohort of 66 consecutive patients underwent cervical Deuk Laser Disc Repair® for one (n = 21) or two adjacent (n = 45) symptomatic levels of cervical disc disease and were evaluated postoperatively for resolution of headache, neck pain, arm pain, and radicular symptoms. All patients were candidates for anterior cervical discectomy and fusion (ACDF) or arthroplasty. The Mann–Whitney Wilcoxon test was used to calculate P values. Results: All patients (n = 66) had significant improvement in preoperative symptoms with an average symptom resolution of 94.6%. Fifty percent (n = 33) had 100% resolution of all preoperative cervicogenic symptoms. Only 4.5% (n = 3) had less than 80% resolution of preoperative symptoms. Visual analog scale (VAS) significantly improved from 8.7 preoperatively to 0.5 postoperatively (P < 0.001) for the cohort. Average operative and recovery times were 57 and 52 minutes, respectively. There were no perioperative complications. Recurrent disc herniation occurred in one patient (1.5%). Average postoperative follow-up was 94 days and no significant intergroup difference in outcomes was observed (P = 0.111) in patients with <90 days (n = 52) or >90 days (n = 14, mean 319 days) follow-up. No significant difference in outcomes was observed (P = 0.774) for patients undergoing one or two level Deuk Laser Disc Repair®. Patients diagnosed with postoperative cervical facet syndrome did significantly worse (P < 0.001). Conclusion: Deuk Laser Disc Repair® is a safe and effective alternative to ACDF or arthroplasty for the treatment of one or two adjacent symptomatic cervical disc herniations with an overall success rate of 94.6%. PMID:23776754

  18. First report of perforation of ligamentum flavum by sequestrated lumbar intervertebral disc

    PubMed Central

    Ozdemir, Bulent; Kanat, Ayhan; Batcik, Osman Ersegun; Erturk, Cihangir; Celiker, Fatma Beyazal; Guvercin, Ali Riza; Yazar, Ugur

    2017-01-01

    Disc fragments are well known to migrate to superior, inferior, or lateral sites in the anterior epidural space, posterior epidural migrated lumbar disc fragments is an extremely rare disorder, 61 cases have been reported to date. However, there were no cases with perforated ligamentum flavum (LF). We report a different case with perforation of ligamentum ligamentum by disc fragment. To the best of our knowledge, this is the first report of perforation LF by a posterior epidural migrated sequester disc. PMID:28250640

  19. Cervical disc arthroplasty with PRESTIGE LP disc versus anterior cervical discectomy and fusion: a prospective, multicenter investigational device exemption study.

    PubMed

    Gornet, Matthew F; Burkus, J Kenneth; Shaffrey, Mark E; Argires, Perry J; Nian, Hui; Harrell, Frank E

    2015-07-31

    OBJECT This study compared the safety and efficacy of treatment with the PRESTIGE LP cervical disc versus a historical control anterior cervical discectomy and fusion (ACDF). METHODS Prospectively collected PRESTIGE LP data from 20 investigational sites were compared with data from 265 historical control ACDF patients in the initial PRESTIGE Cervical Disc IDE study. The 280 investigational patients with single-level cervical disc disease with radiculopathy and/or myelopathy underwent arthroplasty with a low-profile artificial disc. Key safety/efficacy outcomes included Neck Disability Index (NDI), Neck and Arm Pain Numerical Rating Scale scores, 36-Item Short Form Health Survey (SF-36) score, work status, disc height, range of motion, adverse events (AEs), additional surgeries, and neurological status. Clinical and radiographic evaluations were completed preoperatively, intraoperatively, and at 1.5, 3, 6, 12, and 24 months postoperatively. Predefined Bayesian statistical methods with noninformative priors were used, along with the propensity score technique for controlling confounding factors. Analysis by independent statisticians confirmed initial statistical findings. RESULTS The investigational and control groups were mostly similar demographically. There was no significant difference in blood loss (51.0 ml [investigational] vs 57.1 ml [control]) or hospital stay (0.98 days [investigational] vs 0.95 days [control]). The investigational group had a significantly longer operative time (1.49 hours vs 1.38 hours); 95% Bayesian credible interval of the difference was 0.01-0.21 hours. Significant improvements versus preoperative in NDI, neck/arm pain, SF-36, and neurological status were achieved by 1.5 months in both groups and were sustained at 24 months. Patient follow-up at 24 months was 97.1% for the investigational group and 84.0% for the control group. The mean NDI score improvements versus preoperative exceeded 30 points in both groups at 12 and 24 months. SF

  20. Effect of Survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model

    PubMed Central

    Yue, Bin; Lin, Yazhou; Ma, Xuexiao; Zhang, Guoqing; Chen, Bohua

    2016-01-01

    The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration. PMID:27748828

  1. Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging

    PubMed Central

    Nisolle, Jean-François; Bihin, Benoît; Kirschvink, Nathalie; Neveu, Fabienne; Clegg, Peter; Dugdale, Alexandra; Wang, Xiaoqing; Vandeweerd, Jean-Michel

    2016-01-01

    Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration. PMID:27538861

  2. Penetrating annulus fibrosus injuries affect dynamic compressive behaviors of the intervertebral disc via altered fluid flow: an analytical interpretation.

    PubMed

    Michalek, Arthur J; Iatridis, James C

    2011-08-01

    Extensive experimental work on the effects of penetrating annular injuries indicated that large injuries impact axial compressive properties of small animal intervertebral discs, yet there is some disagreement regarding the sensitivity of mechanical tests to small injury sizes. In order to understand the mechanism of injury size sensitivity, this study proposed a simple one dimensional model coupling elastic deformations in the annulus with fluid flow into and out of the nucleus through both porous boundaries and through a penetrating annular injury. The model was evaluated numerically in dynamic compression with parameters obtained by fitting the solution to experimental stress-relaxation data. The model predicted low sensitivity of mechanical changes to injury diameter at both small and large sizes (as measured by low and high ratios of injury diameter to annulus thickness), with a narrow range of high sensitivity in between. The size at which axial mechanics were most sensitive to injury size (i.e., critical injury size) increased with loading frequency. This study provides a quantitative hypothetical model of how penetrating annulus fibrosus injuries in discs with a gelatinous nucleus pulposus may alter disc mechanics by changing nucleus pulposus fluid pressurization through introduction of a new fluid transport pathway though the annulus. This model also explains how puncture-induced biomechanical changes depend on both injury size and test protocol.

  3. The elastic fibre network of the human lumbar anulus fibrosus: architecture, mechanical function and potential role in the progression of intervertebral disc degeneration

    PubMed Central

    Fazzalari, Nicola L.

    2009-01-01

    Elastic fibres are critical constituents of dynamic biological structures that functionally require elasticity and resilience. The network of elastic fibres in the anulus fibrosus of the intervertebral disc is extensive, however until recently, the majority of histological, biochemical and biomechanical studies have focussed on the roles of other extracellular matrix constituents such as collagens and proteoglycans. The resulting lack of detailed descriptions of elastic fibre network architecture and mechanical function has limited understanding of the potentially important contribution made by elastic fibres to healthy disc function and their possible roles in the progression of disc degeneration. In addition, it has made it difficult to postulate what the consequences of elastic fibre related disorders would be for intervertebral disc behaviour, and to develop treatments accordingly. In this paper, we review recent and historical studies which have examined both the structure and the function of the human lumbar anulus fibrosus elastic fibre network, provide a synergistic discussion in an attempt to clarify its potentially critical contribution both to normal intervertebral disc behaviour and the processes relating to its degeneration, and recommend critical areas for future research. PMID:19263091

  4. Management of Chronic Pain of Cervical Disc Herniation and Radiculitis with Fluoroscopic Cervical Interlaminar Epidural Injections

    PubMed Central

    Manchikanti, Laxmaiah; Cash, Kimberly A.; Pampati, Vidyasagar; Wargo, Bradley W.; Malla, Yogesh

    2012-01-01

    Study Design: A randomized, double-blind, active controlled trial. Objective: To evaluate the effectiveness of cervical interlaminar epidural injections of local anesthetic with or without steroids in the management of chronic neck pain and upper extremity pain in patients with disc herniation and radiculitis. Summary of Background Data: Epidural injections in managing chronic neck and upper extremity pain are commonly employed interventions. However, their long-term effectiveness, indications, and medical necessity, of their use and their role in various pathologies responsible for persistent neck and upper extremity pain continue to be debated, even though, neck and upper extremity pain secondary to disc herniation and radiculitis, is described as the common indication. There is also paucity of high quality literature. Methods: One-hundred twenty patients were randomly assigned to one of 2 groups: Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 mL); Group II patients received 0.5% lidocaine, 4 mL, mixed with 1 mL of nonparticulate betamethasone. Primary outcome measure was ≥ 50 improvement in pain and function. Outcome assessments included Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), opioid intake, employment, and changes in weight. Results: Significant pain relief and functional status improvement (≥ 50%) was demonstrated in 72% of patients who received local anesthetic only and 68% who received local anesthetic and steroids. In the successful group of participants, significant improvement was illustrated in 77% in local anesthetic group and 82% in local anesthetic with steroid group. Conclusions: Cervical interlaminar epidural injections with or without steroids may provide significant improvement in pain and function for patients with cervical disc herniation and radiculitis. PMID:22859902

  5. RNA in situ hybridization characterization of non-enzymatic derived bovine intervertebral disc cell lineages suggests progenitor cell potential.

    PubMed

    Kraus, Petra; Yerden, Rachel; Kocsis, Victoria; Lufkin, Thomas

    2017-03-01

    Degeneration of the intervertebral disc (IVD) is a meritorious target for therapeutic cell based regenerative medicine approaches, however, controversy over what defines the precise identity of mature IVD cells and lack of single cell based quality control measures is of concern. Bos taurus and human IVDs are histologically more similar than is Mus musculus. The mature bovine IVD is well suited as model system for technology development to be translated into therapeutic cell based regenerative medicine applications. We present a reproducible non-enzymatic protocol to isolate cell progenitor populations of three distinct areas of the mature bovine IVD. Bovine specific RNA probes were validated in situ and employed to assess fate changes, heterogeneity, stem cell characteristics and differentiation potential of the cultures. Quality control measures with single cell resolution like RNA in situ hybridization to assess culture heterogeneity (PISH) followed by optimization of culture conditions could be translated to human IVD cell culture to increase the safety of cell based regenerative medicine.

  6. Initial clinical experience with a next-generation artificial disc for the treatment of symptomatic degenerative cervical radiculopathy

    PubMed Central

    Reyes-Sanchez, Alejandro; Miramontes, Victor; Olivarez, Luis M. Rosales; Aquirre, Armando Alpizar; Quiroz, Alfredo Ortega; Zarate-Kalfopulos, Baron

    2010-01-01

    Background A feasibility trial was conducted to evaluate the initial safety and clinical use of a next-generation artificial cervical disc (M6-C artificial cervical disc; Spinal Kinetics, Sunnyvale, CA) for the treatment of patients with symptomatic degenerative cervical radiculopathy. A standardized battery of validated outcome measures was utilized to assess condition-specific functional impairment, pain severity, and quality of life. Methods Thirty-six consecutive patients were implanted with the M6-C disc and complete clinical and radiographic outcomes for 25 patients (mean age, 44.5 ± 10.1 years) with radiographically-confirmed cervical disc disease and symptomatic radiculopathy unresponsive to conservative medical management are included in this report. All patients had disc-osteophyte complex causing neural compression and were treated with discectomy and artificial cervical disc replacement at either single level (n = 12) or 2-levels (n = 13). Functional impairment was evaluated using the Neck Disability Index (NDI). Evaluation of arm and neck pain severity utilized a standard 11-point numeric scale, and health-related quality of life was evaluated with the SF-36 Health Survey. Quantitative radiographic assessments of intervertebral motion were performed using specialized motion analysis software, QMA (Quantitative Motion Analysis; Medical Metrics, Houston, TX). All outcome measures were evaluated pre-treatment and at 6 weeks, 3, 6, 12, and 24 months. Results The mean NDI score improved from 51.6 ± 11.3% pre-treatment to 27.9 ± 16.9% at 24 months, representing an approximate 46% improvement (P <.0001). The mean arm pain score improved from 6.9 ± 2.5 pre-treatment to 3.9 ± 3.1 at 24 months (43%, P =.0006). The mean neck pain score improved from 7.8 ± 2.0 pre-treatment to 3.8 ± 3.0 at 24 months (51%, P <.0001). The mean PCS score of the SF-36 improved from 34.8 ± 7.8 pre-treatment to 43.8 ± 9.3 by 24 months (26%, P =.0006). Subgroup analyses found

  7. Form and function of the intervertebral disc in health and disease: a morphological and stain comparison study.

    PubMed

    Walter, B A; Torre, O M; Laudier, D; Naidich, T P; Hecht, A C; Iatridis, J C

    2015-12-01

    Multiple histologic measurements are commonly used to assess degenerative changes in intervertebral disc (IVD) structure; however, there is no consensus on which stains offer the clearest visualization of specific areas within the IVD. The objective of this study was to compare multiple tinctorial stains, evaluate their ability to highlight structural features within the IVD, and investigate how they influence the capacity to implement a degeneration scoring system. Lumbar IVDs from seven human autopsy specimens were stained using six commonly used stains (Hematoxylin/Eosin, Toluidine Blue, Safranin-O/Fast Green, Extended FAST, modified Gomori's Trichrome, and Picrosirius Red Alcian Blue). All IVDs were evaluated by three separate graders to independently determine which stains (i) were most effective at discerning different structural features within different regions of the IVDs and (ii) allowed for the most reproducible assessment of degeneration grade, as assessed via the Rutges histological scoring system (Rutges et al. A validated new histological classification for intervertebral disc degeneration. Osteoarthritis Cartilage, 21, 2039-47). Although Trichrome, XFAST and PR/AB stains were all effective at highlighting different regions of whole IVDs, we recommend the use of PR/AB because it had the highest degree of rater agreement on assigned degeneration grade, allowed greater resolution of degeneration grade, has an inferential relationship between color and composition, and allowed clear differentiation of the different regions and structural disruptions within the IVD. The use of a standard set of stains together with a histological grading scheme can aid in the characterization of structural changes in different regions of the IVD and may simplify comparisons across the field. This collection of human IVD histological images highlights how IVD degeneration is not a single disease but a composite of multiple processes such as aging, injury, repair, and

  8. 2D segmentation of intervertebral discs and its degree of degeneration from T2-weighted magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Castro-Mateos, Isaac; Pozo, José Maria; Lazary, Aron; Frangi, Alejandro F.

    2014-03-01

    Low back pain (LBP) is a disorder suffered by a large population around the world. A key factor causing this illness is Intervertebral Disc (IVD) degeneration, whose early diagnosis could help in preventing this widespread condition. Clinicians base their diagnosis on visual inspection of 2D slices of Magnetic Resonance (MR) images, which is subject to large interobserver variability. In this work, an automatic classification method is presented, which provides the Pfirrmann degree of degeneration from a mid-sagittal MR slice. The proposed method utilizes Active Contour Models, with a new geometrical energy, to achieve an initial segmentation, which is further improved using fuzzy C-means. Then, IVDs are classified according to their degree of degeneration. This classification is attained by employing Adaboost on five specific features: the mean and the variance of the probability map of the nucleus using two different approaches and the eccentricity of the fitting ellipse to the contour of the IVD. The classification method was evaluated using a cohort of 150 intervertebral discs assessed by three experts, resulting in a mean specificity (93%) and sensitivity (83%) similar to the one provided by every expert with respect to the most voted value. The segmentation accuracy was evaluated using the Dice Similarity Index (DSI) and Root Mean Square Error (RMSE) of the point-to-contour distance. The mean DSI ± 2 standard deviation was 91:7% ±5:6%, the mean RMSE was 0:82mm and the 95 percentile was 1:36mm. These results were found accurate when compared to the state-of-the-art.

  9. Evaluation of a new approach to compute intervertebral disc height measurements from lateral radiographic views of the spine

    PubMed Central

    Kaluza, M. Clara DePaolis; Bruno, Alexander G.; Samelson, Elizabeth J.; Kiel, Douglas P.; Anderson, Dennis E.; Bouxsein, Mary L.

    2017-01-01

    Purpose Current standard methods to quantify disc height, namely distortion compensated Roentgen analysis (DCRA), have been mostly utilized in the lumbar and cervical spine and have strict exclusion criteria. Specifically, discs adjacent to a vertebral fracture are excluded from measurement, thus limiting the use of DCRA in studies that include older populations with a high prevalence of vertebral fractures. Thus, we developed and tested a modified DCRA algorithm that does not depend on vertebral shape. Methods Participants included 1186 men and women from the Framingham Heart Study Offspring and Third Generation Multidetector CT Study. Lateral CT scout images were used to place 6 morphometry points around each vertebra at 13 vertebral levels in each participant. Disc heights were calculated utilizing these morphometry points using DCRA methodology and our modified version of DCRA, which requires information from fewer morphometry points than the standard DCRA. Results Modified DCRA and standard DCRA measures of disc height are highly correlated, with concordance correlation coefficients above 0.999. Both measures demonstrate good inter- and intra-operator reproducibility. 13.9 % of available disc heights were not evaluable or excluded using the standard DCRA algorithm, while only 3.3 % of disc heights were not evaluable using our modified DCRA algorithm. Conclusions Using our modified DCRA algorithm, it is not necessary to exclude vertebrae with fracture or other deformity from disc height measurements as in the standard DCRA. Modified DCRA also yields identical measurements to the standard DCRA. Thus, the use of modified DCRA for quantitative assessment of disc height will lead to less missing data without any loss of accuracy, making it a preferred alternative to the current standard methodology. PMID:27757680

  10. The Effect of Discectomy and the Dependence on Degeneration of Human Intervertebral Disc Strain in Axial Compression

    PubMed Central

    O’Connell, Grace D.; Malhotra, Neil R.; Vresilovic, Edward J; Elliott, Dawn M.

    2011-01-01

    Study Design Biomechanics of human intervertebral discs before and after nucleotomy. Objective To noninvasively quantify the effect of nucleotomy on internal strains under axial compression in flexion, neutral, and extension positions, and to determine whether the change in strains depended on degeneration. Summary of Background Data Herniation and discectomy may accelerate the progression of disc degeneration. Removal of NP tissue has resulted in altered disc mechanics in vitro, including in a decrease in internal pressure and an increase in the deformations at physiologically relevant strains. We recently presented a technique to quantify internal disc strains using magnetic resonance imaging. Methods Degeneration was quantitatively assessed by the T1ρ relaxation in the nucleus pulposus (NP). Samples were prepared from human levels L3-L4 and/or L4-L5. A 1000N compressive load was applied while in the MR scanner. Nucleotomy was performed by removing 2g of NP through the posterior-lateral AF. The discs were rehydrated, reimaged and retested. The analyzed parameters include axial deformation, AF radial bulge and strains. Results The axial deformation was more compressive following nucleotomy. In the neutral position, the axial deformation following nucleotomy correlated with degeneration (as quantified by T1ρ in the NP), with minimal alteration in nondegenerated discs. Nucleotomy altered the radial displacements and strains in the neutral position, such that the inner AF radial bulge decreased and the radial strains were more tensile in the lateral AF and less tensile in the posterior AF. In the bending loading positions the radial strains were not affected by nucleotomy. Conclusions Nucleotomy alters the internal radial and axial AF strains in the neutral position, which may leave the AF vulnerable to damage and microfractures. In bending, the effects of nucleotomy were minimal; likely due to more of the applied load being directed over the AF. Some of the

  11. 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model.

    PubMed

    Osti, O L; Vernon-Roberts, B; Fraser, R D

    1990-08-01

    An animal model was developed to test the hypothesis that discrete peripheral tears within the anulus lead to secondary degenerative changes in other disc components. In 21 adult sheep, a cut was made in the left anterolateral anulus of three randomly selected lumbar discs. The cut was parallel and adjacent to the inferior end-plate, and had a controlled depth of 5 mm. This left the inner third of the anulus and the nucleus pulposus intact and closely reproduced the rim Lear lesion described by Schmorl. Animals were randomly allocated to different groups in relation to the length of time interval between operation and death, varying from 1 to 18 months. At death, the lumbar spine was cut into individual joint units and each disc sectioned into six parasagittal slabs. After observation of the slabs under the dissecting microscope, two of the six slabs, the one containing the anulus lesion and a contralateral, were processed for histology. The results of this study suggest that, despite the great care taken at operation to ensure that the inner anulus was left intact, progressive failure of the inner anulus was seen in all sheep and occurred in the majority of discs between 4 and 12 months after the operation. Although the outermost anulus showed the ability to heal, the defect induced by the cut led initially to deformation and bulging of the collagen bundles, and eventually to inner extension of the tear and complete failure. These findings suggest that discrete tears of the outer anulus may have a role in the formation of concentric clefts and in accelerating the development of radiating clefts. Peripheral tears of the anulus fibrosus therefore may play an important role in the degeneration of the intervertebral joint complex.

  12. Efficacy of intervertebral disc regeneration with stem cells - a systematic review and meta-analysis of animal controlled trials.

    PubMed

    Wang, Zhen; Perez-Terzic, Carman M; Smith, Jay; Mauck, William D; Shelerud, Randy A; Maus, Timothy P; Yang, Tai-Hua; Murad, Mohammad Hassan; Gou, Shanmiao; Terry, Marisa J; Dauffenbach, Jason P; Pingree, Mathew J; Eldrige, Jason S; Mohammed, Khaled; Benkhadra, Khalid; van Wijnen, Andre J; Qu, Wenchun

    2015-06-10

    Management of intervertebral disc (IVD) degenerative disease is challenging, as it is accompanied by irreversible loss of IVD cells. Stem cell transplantation to the disc has shown promise in decelerating or arresting the degenerative process. Multiple pre-clinical animal trials have been conducted, but with conflicting outcomes. To assess the effect of stem cell transplantation, a systematic review and meta-analysis was performed. A comprehensive literature search was conducted through Week 3, 2015. Inclusion criteria consisted of controlled animal trials. Two reviewers screened abstracts and full texts. Disagreements were resolved by a third reviewer. Random effects models were constructed to pool standardized mean difference (SMD). Twenty two studies were included; nine of which were randomized. Statistically significant differences were found with the stem cell group exhibiting increased disc height index (SMD=3.64, 95% confidence interval (CI): 2.49, 4.78; p<0.001), increased MRI T2 signal intensity (SMD=2.28, 95% CI: 1.48, 3.08; p<0.001), increased Type II collagen mRNA expression (SMD=3.68, 95% CI: 1.66, 5.70; p<0.001), and decreased histologic disc degeneration grade (SMD=-2.97, 95% CI: -3.97, -1.97; p<0.001). There was statistical heterogeneity between studies that could not be explained with pre-planned subgroup analyses based on animal species, study designs, and transplanted cell types. Stem cells transplanted to the IVD in quadruped animals decelerate or arrest the IVD degenerative process. Further studies in human clinical trials will be needed to understand if such benefit can be translated to bipedal humans.

  13. Lumbar intervertebral discs T2 relaxometry and T1ρ relaxometry correlation with age in asymptomatic young adults

    PubMed Central

    Salmon, Carlos E. Garrido; Bonugli, Gustavo P.; Mazoroski, Debora; Tamashiro, Mauricio H.; Savarese, Leonor G.; Nogueira-Barbosa, Marcello Henrique

    2016-01-01

    Background To investigate the detection of intervertebral disc (IVD) composition aging-related changes using T2 and T1ρ relaxometry in vivo in asymptomatic young adults. Methods We recruited ninety asymptomatic and young adults (42 men and 48 women) between 20 and 40 years old. T2 and T1ρ lumbar spine mappings were acquired using 1.5 T magnetic resonance imaging (MRI) scanner. Two independent observers manually segmented 450 lumbar discs in all slices. They also performed sub region segmentation of annulus fibrosus (AF) and nucleus pulposus (NP) at the central MRI sagittal slices. Results There was no difference between men and women for T2 (P=0.37) or T1ρ relaxometry (P=0.97). There was a negative correlation between age (20–40 years) and IVD T2 relaxation time of the whole disc (r=−0.30, P<0.0001), NP (r=−0.20 to −0.51, P<0.05) and posterior AF (r=−0.21 to −0.31, P<0.05) at all lumbar disc levels. There was no statistical correlation between aging and IVD T1ρ relaxation both for NP and AF. Conclusions T2 relaxometry detected gradual IVD dehydration in the first two decades of adulthood. We observed no significant variation of T1ρ or volumetry with aging in our study group. Our results suggest that T2 mapping may be more appropriate to detect early IVD aging changes. PMID:27709076

  14. RT97- and calcitonin gene-related peptide-like immunoreactivity in lumbar intervertebral discs and adjacent tissue from the rat.

    PubMed Central

    McCarthy, P W; Petts, P; Hamilton, A

    1992-01-01

    The innervation of rat intervertebral disc and adjacent ligamentous tissue has been investigated using 2 antibodies, RT97 and anti-calcitonin gene-related peptide. Immunoreactivity to the peptide was found in many fibres throughout the long ligaments around the intervertebral discs and in the periosteum, especially associated with vascular channels entering the vertebral bodies. Few of the immunoreactive fibres entered the annular lamellae of the disc tissue. Most of those which terminated did so as fine fibres which lay close to, or in, the interlamellar spaces of the outer annulus fibrosus. Calcitonin gene-related peptide-like immunoreactivity was also found in more complex endings in the longitudinal ligaments and rarely within the annulus fibrosus. RT97-immunoreactivity was also present in the complex endings and associated fibres. Conversely, RT97-immunoreactivity was apparent only in a few fine filamentous fibre endings. This suggested that the majority of fine filamentous, or free, nerve endings were of an unmyelinated sensory origin. Alternatively, those endings of a more complex nature, which were RT97-immunoreactive, were of a myelinated sensory origin. No immunoreactivity to either antibody was seen in the inner annular or nuclear tissue. It was therefore concluded that the sensory innervation of the rat intervertebral disc has both myelinated and unmyelinated components, the latter being more extensive. Both types of innervation appear to be restricted to the outermost rings of the annulus fibrosus. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1452470

  15. Narrowing of lumbar spinal canal predicts chronic low back pain more accurately than intervertebral disc degeneration: a magnetic resonance imaging study in young Finnish male conscripts.

    PubMed

    Visuri, Tuomo; Ulaska, Jaana; Eskelin, Marja; Pulkkinen, Pekka

    2005-11-01

    The objective of this magnetic resonance imaging study was to evaluate the role of degenerative changes, developmental spinal stenosis, and compression of spinal nerve roots in chronic low back (CLBP) and radicular pain in Finnish conscripts. The degree of degeneration, protrusion, and herniation of the intervertebral discs and stenosis of the nerve root canals was evaluated, and the midsagittal diameter and cross-sectional area of the lumbar vertebrae canal were measured in 108 conscripts with CLBP and 90 asymptomatic controls. The midsagittal diameters at L1-L4 levels were significantly smaller in the patients with CLBP than in the controls. Moreover, degeneration of the L4/5 disc and protrusion or herniation of the L5/S1 disc and stenosis of the nerve root canals at level L5/S1 were more frequent among the CLBP patients. Multifactorial analysis of the magnetic resonance imaging findings provided a total explanatory rate of only 33%. Narrowing of the vertebral canal in the anteroposterior direction was more likely to produce CLBP and radiating pain than intervertebral disc degeneration or narrowing of the intervertebral nerve root canals.

  16. Magnetic resonance imaging diagnosis of intervertebral disc disease and myelomalacia in an American black bear (Ursus americanus).

    PubMed

    Knafo, S Emmanuelle; Divers, Stephen J; Rech, Raquel; Platt, Simon R

    2012-06-01

    A 23-yr-old black bear (Ursus americanus) was examined because of paralysis of unknown duration. The precise onset of clinical signs was unknown as a result of seasonal torpor. The bear was immobilized and transported to a university veterinary teaching hospital for further evaluation and treatment. Radiography revealed increased mineral opacity and ventral bridging across vertebral segments T8-11. Magnetic resonance imaging demonstrated dorsal and ventral compression of the spinal cord at T8-9. Given the bear's advanced age, the unknown duration of spinal cord compression, unknown presence of deep pain perception, and thus an unknown prognosis for surgical success, euthanasia was elected. Postmortem examination revealed severe spondylosis deformans from T7 to L3 and dorsal extradural extruded disc material in the area of T8-9. Histopathology demonstrated the dorsal horns of the spinal cord at T9 were replaced by foamy macrophages extending into the dorsal and lateral funiculi of the white matter compatible with focal, severe, chronic myelomalacia. This is the first report of intervertebral disc disease and myelomalacia diagnosed using MRI in a large carnivore.

  17. Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration

    PubMed Central

    Hu, Bo; Shi, Changgui; Xu, Chen; Cao, Peng; Tian, Ye; Zhang, Ying; Deng, Lianfu; Chen, Huajiang; Yuan, Wen

    2016-01-01

    Intervertebral disc degeneration (IDD) is characterized by disordered extracellular matrix (ECM) metabolism, implicating subdued anabolism and enhanced catabolic activities in the nucleus pulposus (NP) of discs. Pro-inflammatory cytokines such as interleukin-1β (IL-1β) are considered to be potent mediators of ECM breakdown. Hemeoxygenase-1 (HO-1) has been reported to participate in cellular anti-inflammatory processes. The purpose of this study was to investigate HO-1 modulation of ECM metabolism in human NP cells under IL-1β stimulation. Our results revealed that expression of HO-1 decreased considerably during IDD progression. Induction of HO-1 by cobalt protoporphyrin IX attenuated the inhibition of sulfate glycosaminoglycan and collagen type II (COL-II) synthesis and ameliorated the reduced expressions of aggrecan, COL-II, SOX-6 and SOX-9 mediated by IL-1β. Induction of HO-1 also reversed the effect of IL-1β on expression of the catabolic markers matrix metalloproteinases-1, 3, 9 and 13. This was combined with inhibition of the activation of mitogen-activated protein kinase signaling. These findings suggest that HO-1 might play a pivotal role in IDD, and that manipulating HO-1 expression might mitigate the impairment of ECM metabolism in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD. PMID:26877238

  18. Effect of Static Load on the Nucleus Pulposus of Rabbit Intervertebral Disc Motion Segment in an Organ Culture

    PubMed Central

    Feng, Min-Shan; Zhang, Ping; Yu, Jie

    2016-01-01

    The development of mechanically active culture systems helps in understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures facilitate the application and control of mechanical loads. The purpose of this study was to establish a culturing method for rabbit IVD motion segments to observe the effect of static load on the whole disc organ. Segments were cultured in custom-made apparatuses under a constant, compressive load (3 kg) for 2 weeks. Tissue integrity, matrix synthesis, and matrix gene expression profile were assessed and compared with fresh one. The results showed ex vivo culturing of samples gradually destroyed the morphology. Proteoglycan contents and gene expression were decreased and downregulated obviously. However, immunohistochemical staining intensity and collagen type II gene expression were significantly enhanced and upregulated. In contrast, these trends were reversed under constant compression. These results indicated short-term static load stimulated the synthesis of type II collagen; however, constant compression led to progressive degeneration and specifically to proteoglycan. Through this study a loading and organ-culturing system for ex vivo rabbit IVD motion segments was developed, which can be used to study the effects of mechanical stimulation on the biology of IVDs and the pathomechanics of IVD degeneration. PMID:27872846

  19. Microscale Material Properties of Bone and the Mineralized Tissues of the Intervertebral Disc-Vertebral Body Interface

    NASA Astrophysics Data System (ADS)

    Paietta, Rachel C.

    The objective of this dissertation is to understand the influences of material structure on the properties, function and failure of biological connective tissues. Biological interfaces are becoming an increasingly studied system within mechanics and tissue engineering as a model for attaching dissimilar materials. The elastic modulus of bone (≈ 20 GPa) and cartilage (≈ 0.1-1 MPa) differ over orders of magnitude, which should intuitively create high stress concentrations and failure at the interface. Yet, these natural interface systems rarely fail in vivo, and the mechanism by which loads are transferred between tissues has not yet been established. Tissue quality is one major contributor to the mechanical behavior of bone and cartilage, and is defined by properties such as collagen orientation, mineral volume fraction, porosity and tissue geometry. These properties have yet to be established at the bone-cartilage interface in the spine, and the lack of quantitative data on material microstructure and behavior limits treatments and tissue engineering construct design. In this dissertation, second harmonic generation imaging, quantitative backscattered scanning electron imaging and nanoindentation are combined to characterize micrometer scale tissue quality and modulus in both bone and calcified cartilage. These techniques are utilized to: 1) determine the hierarchical micrometer to millimeter scale properties of lamellar bone, 2) quantify changes throughout development and aging at the human intervertebral disc-vertebral body junction, and 3) explore compressive fractures at this interface. This work is the first to provide quantitative data on the mineral volume fraction, collagen orientation and modulus from the same, undecalcified sections of tissue to corroborate tissue structure and mineralization and describe quantitative parameters of the interface. The principal findings from this work indicate that the underlying matrix, or collagen, organization in

  20. Validation and application of an intervertebral disc finite element model utilizing independently constructed tissue-level constitutive formulations that are nonlinear, anisotropic, and time-dependent.

    PubMed

    Jacobs, Nathan T; Cortes, Daniel H; Peloquin, John M; Vresilovic, Edward J; Elliott, Dawn M

    2014-08-22

    Finite element (FE) models are advantageous in the study of intervertebral disc mechanics as the stress-strain distributions can be determined throughout the tissue and the applied loading and material properties can be controlled and modified. However, the complicated nature of the disc presents a challenge in developing an accurate and predictive disc model, which has led to limitations in FE geometry, material constitutive models and properties, and model validation. The objective of this study was to develop a new FE model of the intervertebral disc, to validate the model's nonlinear and time-dependent responses without tuning or calibration, and to evaluate the effect of changes in nucleus pulposus (NP), cartilaginous endplate (CEP), and annulus fibrosus (AF) material properties on the disc mechanical response. The new FE disc model utilized an analytically-based geometry. The model was created from the mean shape of human L4/L5 discs, measured from high-resolution 3D MR images and averaged using signed distance functions. Structural hyperelastic constitutive models were used in conjunction with biphasic-swelling theory to obtain material properties from recent tissue tests in confined compression and uniaxial tension. The FE disc model predictions fit within the experimental range (mean ± 95% confidence interval) of the disc's nonlinear response for compressive slow loading ramp, creep, and stress-relaxation simulations. Changes in NP and CEP properties affected the neutral-zone displacement but had little effect on the final stiffness during slow-ramp compression loading. These results highlight the need to validate FE models using the disc's full nonlinear response in multiple loading scenarios.

  1. Morphometric analysis of the relationships between intervertebral disc and vertebral body heights: an anatomical and radiographic study of the human thoracic spine

    PubMed Central

    Kunkel, Maria E; Herkommer, Andrea; Reinehr, Michael; Böckers, Tobias M; Wilke, Hans-Joachim

    2011-01-01

    The main aim of this study was to provide anatomical data on the heights of the human intervertebral discs for all levels of the thoracic spine by direct and radiographic measurements. Additionally, the heights of the neighboring vertebral bodies were measured, and the prediction of the disc heights based only on the size of the vertebral bodies was investigated. The anterior (ADH), middle (MDH) and posterior heights (PDH) of the discs were measured directly and on radiographs of 72 spine segments from 30 donors (age 57.43 ± 11.27 years). The radiographic measurement error and the reliability of the measurements were calculated. Linear and non-linear regression analyses were employed for investigation of statistical correlations between the heights of the thoracic disc and vertebrae. Radiographic measurements displayed lower repeatability and were shorter than the anatomical ones (approximately 9% for ADH and 37% for PDH). The thickness of the discs varied from 4.5 to 7.2 mm, with the MDH approximately 22.7% greater. The disc heights showed good correlations with the vertebral body heights (R2, 0.659–0.835, P-values < 0.005; anova), allowing the generation of 10 prediction equations. New data on thoracic disc morphometry were provided in this study. The generated set of regression equations could be used to predict thoracic disc heights from radiographic measurement of the vertebral body height posterior. For the creation of parameterized models of the human thoracic discs, the use of the prediction equations could eliminate the need for direct measurement on intervertebral discs. Moreover, the error produced by radiographic measurements could be reduced at least for the PDH. PMID:21615399

  2. The use of a novel injectable hydrogel nucleus pulposus replacement in restoring the mechanical properties of cyclically fatigued porcine intervertebral discs.

    PubMed

    Balkovec, Christian; Vernengo, Jennifer; McGill, Stuart M

    2013-06-01

    Repeated flexion and extension of an intervertebral disc has been shown to affect the angular stiffness of spinal motion segments and is a barometer of the mechanical integrity of the disc. A degenerated disc that loses height causes higher levels of stress on the annulus and facet joints which may increase its level of degeneration; restoring disc height may therefore help to slow this degenerative cascade. Previous research has indicated that nucleus implants have the potential to improve the mechanical characteristics of a disc and an implant that is custom-fit to the intervertebral disc yields the best results with respect to decreasing annular degeneration. Two groups of porcine spinal motion segments were exposed to repeated flexion and extension. One group was then injected with a novel hydrogel while the other group was used as a control. Both groups were then exposed to another round of cyclic flexion and extension to examine the effect that the hydrogel had on restoring the original mechanics to the motion segments. Angular stiffness was restored to the group which received the hydrogel injection in addition to a significant improvement in specimen height. No significant changes were seen in the group which did not receive an injection. It would appear that use of the novel injectable hydrogel is able to restore angular stiffness to cyclically fatigued spinal motion segments. It is also important to note that continued repetition of the event causing specimen fatigue after performing hydrogel injection will result in an eventual return to the same fatigued state.

  3. Long term preservation of motion with artificial cervical disc implants: A comparison between cervical disc replacement and rigid fusion with cage

    PubMed Central

    Cincu, Rafael; Lorente, Francisco de Asis; Gomez, Joaquin; Eiras, Jose; Agrawal, Amit

    2014-01-01

    Background: With the advancement of technologies there is more interest in the maintenance of the spine's biomechanical properties focusing on the preservation of the functional motion segment. In present article we describe our experience with 25 cases managed with artificial cervical discs with 28 Solis cage following cervical discectomy with a mean follow-up period of 7.5 year. Materials and Methods: All surgeries were performed by single surgeon from March 2004 to June 2005 with a follow-up till date. Patients with symptomatic single or multiple level diseases that had no prior cervical surgery were candidates for the study. Cohort demographics were comparable. Standardized clinical outcome measures and radiographic examinations were used at prescribed post-operative intervals to compare the treatment groups. Relief in radicular pain, cervical spine motion, and degenerative changes at follow-up were noted. Results: In a total 53 cases, the mean age in prosthesis group was 47 years (age range: 30-63 years) and mean age in cage group was 44 years (32-62 years). Mean hospital stay was 2.7 days in both the groups. At 4 weeks complete cervical movements could be achieved in 19 cases in artificial disc group. Maintenance of movement after 7.5 years was in 76% of these patients. Lordosis was maintained in all cases till date. There was no mortality or wound infection in our series. Conclusions: We conclude that artificial cervical disc could be an alternative to fixed spinal fusion as it represents the most physiological substitute of disc. However, there is need for further studies to support the use of artificial cervical disc prosthesis. PMID:25685218

  4. Cervical Disc Arthroplasty with Prestige LP Disc Versus Anterior Cervical Discectomy and Fusion: Seven-Year Outcomes

    PubMed Central

    Burkus, J. Kenneth; Shaffrey, Mark E.; Nian, Hui; Harrell, Frank E.

    2016-01-01

    Background Cervical disc arthroplasty (CDA) has emerged as an alternative to anterior cervical discectomy and fusion (ACDF) for the treatment of cervical pathologies. Studies are on-going to assess the long term outcomes of CDA. This study assessed the safety and efficacy of the Prestige® LP Disc at 84-months follow up. Methods Prospective data from 280 CDA patients with single-level cervical disc disease with radiculopathy or myelopathy were compared with 265 historical control ACDF patients. Clinical and radiographic follow up was completed pre-operatively, intraoperatively, and at intervals up to 84 months. Results Follow-up rate was 75.9% for CDA and 70.0% for ACDF patients. Statistical improvements (p < 0.001) in Neck Disability Index (NDI), neck/arm pain, and SF-36 were achieved by 1.5 months in both groups and maintained through 84 months. At 84 months, 86.1% of CDA versus 80.1% of ACDF patients achieved NDI success, (≥15-point improvement over baseline). Mean NDI score improvements exceeded 30 points in both groups. SF-36 PCS/MCS mean improvements were 13.1±11.9/8.2±12.3 points for CDA and 10.7±11.8/8.3±13.6 points for ACDF. Neurological success was 92.8% for CDA and 79.7% for ACDF patients. The rate of Overall Success was 74.9% for CDA and 63.2% for ACDF. At 84 months, 17.5% of CDA and 16.6% of ACDF patients had a possibly implant- or implant-surgical procedure-related adverse event. Eighteen (6.4%) CDA and 29 (10.9%) ACDF patients had a second surgery at the index level. In CDA patients, mean angular motion at the target level was maintained at 24 (7.5°) and 84 (6.9°) months. Bridging bone was reported in 5.9%/9.5%/10.2%/13.0% of CDA patients at 24/36/60/84 months. Change in mean preoperative angulation of the adjacent segment above/below the index level was1.06±4.39/1.25±4.06 for CDA and (-0.23)±5.37/1.25±5.07 for ACDF patients. At 84 months, 90.9% of CDA and 85.6% of ACDF patients were satisfied with the results of their treatment

  5. Design and fabrication of 3D-printed anatomically shaped lumbar cage for intervertebral disc (IVD) degeneration treatment.

    PubMed

    Serra, T; Capelli, C; Toumpaniari, R; Orriss, I R; Leong, J J H; Dalgarno, K; Kalaskar, D M

    2016-07-19

    Spinal fusion is the gold standard surgical procedure for degenerative spinal conditions when conservative therapies have been unsuccessful in rehabilitation of patients. Novel strategies are required to improve biocompatibility and osseointegration of traditionally used materials for lumbar cages. Furthermore, new design and technologies are needed to bridge the gap due to the shortage of optimal implant sizes to fill the intervertebral disc defect. Within this context, additive manufacturing technology presents an excellent opportunity to fabricate ergonomic shape medical implants. The goal of this study is to design and manufacture a 3D-printed lumbar cage for lumbar interbody fusion. Optimisations of the proposed implant design and its printing parameters were achieved via in silico analysis. The final construct was characterised via scanning electron microscopy, contact angle, x-ray micro computed tomography (μCT), atomic force microscopy, and compressive test. Preliminary in vitro cell culture tests such as morphological assessment and metabolic activities were performed to access biocompatibility of 3D-printed constructs. Results of in silico analysis provided a useful platform to test preliminary cage design and to find an optimal value of filling density for 3D printing process. Surface characterisation confirmed a uniform coating of nHAp with nanoscale topography. Mechanical evaluation showed mechanical properties of final cage design similar to that of trabecular bone. Preliminary cell culture results showed promising results in terms of cell growth and activity confirming biocompatibility of constructs. Thus for the first time, design optimisation based on computational and experimental analysis combined with the 3D-printing technique for intervertebral fusion cage has been reported in a single study. 3D-printing is a promising technique for medical applications and this study paves the way for future development of customised implants in spinal

  6. Postfusion magnetic resonance imaging artifacts caused by a titanium, cobalt-chromium-molybdenum, and carbon intervertebral disc spacer.

    PubMed

    Ernstberger, Thorsten; Heidrich, Gabert

    2007-04-01

    Intervertebral spacers for anterior spine fusion are made of different materials, such as titanium and CoCrMo-alloys or carbon fiber reinforced polymers (CFRP). Implant-related susceptibility artifacts can decrease the quality of magnetic resonance imaging (MRI) scans. This cadaveric study aimed to demonstrate the extent that implant-related MRI artifacting affects the postfusion differentiation of the spinal canal (SC) and intervertebral disc space (IDS). In 6 cadaveric porcine spines, we evaluated the postimplantation MRI scans of a titanium, CoCrMo-spacer and CFRP-spacer that differed in shape and surface qualities. A spacer made of human cortical bone was used as a control. A defined evaluation unit was divided into regions of interest (ROI) to characterize the SC and IDS. Considering 15 different MRI sequences read independently by an interobserver-validated team of specialists artifact-affected image quality of the median MRI slice was rated on a score of 0-1-2-3. A maximum score of 15 points for the SC and 9 points for the IDS (100%) was possible. Turbo spin echo sequences produced the best scores for both spacers and the control. Only the control achieved a score of 100%. For the IDS the CoCrMo-spacer, titanium and CFRP-spacer maximally scored 0%, 0% and 74%, for the SC 60%, 80% and 99%, respectively. By using favored T1 TSE sequences the CFRP-spacer represented clear advantages in postfusion spinal imaging. Independent of artifact dimensions the used scoring system allowed us to create an implant-related ranking of MRI scan quality in reference to the bone control.

  7. Mechanical performance of cervical intervertebral body fusion devices: A systematic analysis of data submitted to the Food and Drug Administration.

    PubMed

    Peck, Jonathan H; Sing, David C; Nagaraja, Srinidhi; Peck, Deepa G; Lotz, Jeffrey C; Dmitriev, Anton E

    2017-02-01

    Cervical intervertebral body fusion devices (IBFDs) are utilized to provide stability while fusion occurs in patients with cervical pathology. For a manufacturer to market a new cervical IBFD in the United States, substantial equivalence to a cervical IBFD previously cleared by FDA must be established through the 510(k) regulatory pathway. Mechanical performance data are typically provided as part of the 510(k) process for IBFDs. We reviewed all Traditional 510(k) submissions for cervical IBFDs deemed substantially equivalent and cleared for marketing from 2007 through 2014. To reduce sources of variability in test methods and results, analysis was restricted to cervical IBFD designs without integrated fixation, coatings, or expandable features. Mechanical testing reports were analyzed and results were aggregated for seven commonly performed tests (static and dynamic axial compression, compression-shear, and torsion testing per ASTM F2077, and subsidence testing per ASTM F2267), and percentile distributions of performance measurements were calculated. Eighty-three (83) submissions met the criteria for inclusion in this analysis. The median device yield strength was 10,117N for static axial compression, 3680N for static compression-shear, and 8.6Nm for static torsion. Median runout load was 2600N for dynamic axial compression, 1400N for dynamic compression-shear, and ±1.5Nm for dynamic torsion. In subsidence testing, median block stiffness (Kp) was 424N/mm. The mechanical performance data presented here will aid in the development of future cervical IBFDs by providing a means for comparison for design verification purposes.

  8. Hybrid Surgery Versus Anterior Cervical Discectomy and Fusion in Multilevel Cervical Disc Diseases: A Meta-Analysis.

    PubMed

    Zhang, Jianfeng; Meng, Fanxin; Ding, Yan; Li, Jie; Han, Jian; Zhang, Xintao; Dong, Wei

    2016-05-01

    To investigate the outcomes and reliability of hybrid surgery (HS) versus anterior cervical discectomy and fusion (ACDF) for the treatment of multilevel cervical spondylosis and disc diseases.Hybrid surgery, combining cervical disc arthroplasty (CDA) with fusion, is a novel treatment to multilevel cervical degenerated disc disease in recent years. However, the effect and reliability of HS are still unclear compared with ACDF.To investigate the studies of HS versus ACDF in patients with multilevel cervical disease, electronic databases (Medline, Embase, Pubmed, Cochrane library, and Cochrane Central Register of Controlled Trials) were searched. Studies were included when they compared HS with ACDF and reported at least one of the following outcomes: functionality, neck pain, arm pain, cervical range of motion (ROM), quality of life, and incidence of complications. No language restrictions were used. Two authors independently assessed the methodological quality of included studies and extracted the relevant data.Seven clinical controlled trials were included in this study. Two trials were prospective and the other 5 were retrospective. The results of the meta-analysis indicated that HS achieved better recovery of NDI score (P = 0.038) and similar recovery of VAS score (P = 0.058) compared with ACDF at 2 years follow-up. Moreover, the total cervical ROM (C2-C7) after HS was preserved significantly more than the cervical ROM after ACDF (P = 0.000) at 2 years follow-up. Notably, the compensatory increase of the ROM of superior and inferior adjacent segments was significant in ACDF groups at 2-year follow-up (P < 0.01), compared with HS.The results demonstrate that HS provides equivalent outcomes and functional recovery for cervical disc diseases, and significantly better preservation of cervical ROM compared with ACDF in 2-year follow-up. This suggests the HS is an effective alternative invention for the treatment of multilevel cervical spondylosis to

  9. Outcomes of single-level cervical disc arthroplasty versus anterior cervical discectomy and fusion.

    PubMed

    Tracey, Robert W; Kang, Daniel G; Cody, John P; Wagner, Scott C; Rosner, Michael K; Lehman, Ronald A

    2014-11-01

    Several studies have established the short-term safety and efficacy of cervical disc arthroplasty (CDA) as compared to anterior cervical discectomy and fusion (ACDF). However, few single-center comparative trials have been performed, and current studies do not contain large numbers of patients. We retrospectively reviewed all patients from a single military tertiary medical center between August 2008 to August 2012 who underwent single-level CDA or single-level ACDF and compared their clinical outcomes and complications. A total of 259 consecutive patients were included in the study, 171 patients in the CDA group with an average follow-up of 9.8 (±9.9)months and 88 patients in the ACDF group with an average follow-up of 11.8 (±9.6)months. Relief of pre-operative symptoms was 90.1% in the CDA group and 86.4% in the ACDF group with rates of return to full pre-operative activity of 93.0% and 88.6%, respectively. Patients who underwent CDA had a higher rate of persistent posterior neck pain (15.8% versus 12.5%), and patients who underwent ACDF were at risk for symptomatic pseudarthrosis at a rate of 3.4%. Reoperation rates were higher in the ACDF group (5.7% versus 3.5%). To our knowledge, this review is the largest, non-funded, comparison study between single-level CDA and single-level ACDF. This study demonstrates that CDA is a safe and reliable alternative to ACDF in the treatment of cervical radiculopathy and myelopathy resulting from spondylosis and acute disc herniation.

  10. Lack of Relationship Between Occupational Workload and Microscopic Alterations in Lumbar Intervertebral Disc Disease

    PubMed Central

    Huschak, Gerald; Holzhausen, Hans-Jürgen; Beier, Andre; Meisel, Hans Jörg; Hoell, Thomas

    2014-01-01

    Objectives : The study investigated the impact of occupational workloads on disc surgery specimens. We report the relationship between workload and histological features. Methods : Specimens were collected prospectively from patients suffering from lumbar disc prolapse (n=90) or spinal osteochondrosis (n=19). Histomorphology and occupational workload data and histomorphological features were evaluated. Occupational data were collected in a structured, standardized patient interview assessing lifting and carrying loads. In this way the exposure was assessed for each test subject's entire working life up to surgery. Results : There was no association between cumulative workload and histological patterns. In a subgroup of patients with a workload period of 12 months prior to surgery a relevant formation of chondrocyte clusters (p=0.055) was apparent. Chondrocyte cluster formation was found in 83% (n=74) of the prolapse patients and in 58% (n=11) of the osteochondrosis patients (p=0.02). Fibrocyte mediated scar formation was found in 55% of the prolapse patients and in 45% of the spinal stenosis patients. Chondrocyte clusters and their de novo collagen matrix did not integrate biomechanically sufficient with collagen fibers of the disc. Disintegration of clusters from disc matrix and formation of intra-discal sequesters were observed. Conclusion : Matrix degeneration was common but displayed no relationship to occupational workload or other histological features. Scar formation was observed in every second specimen. Regenerative chondrocyte cluster proliferation was a common feature in disc specimens and tended to be associated in patients with a workload one year before surgery. PMID:25136392

  11. Brown-Sequard syndrome produced by calcified herniated cervical disc and posterior vertebral osteophyte: Case report

    PubMed Central

    Guan, Dawei; Wang, Guanjun; Clare, Morgan; Kuang, Zhengda

    2015-01-01

    Brown-Sequard syndrome (BSS) produced by cervical disc disorders has rarely been seen clinically and only 50 cases have been reported in English literatures. However, most of which have resulted from acute disc herniation. Here, we report a case of BSS produced by calcified herniated C4-C5 disc and posterior vertebral osteophyte, in which decompression through anterior approach was performed. This case revealed the potential of cervical spondylopathy leading to BSS in a chronic manner. Once the diagnosis is established, it is advisable to perform decompression as early as possible. PMID:27047233

  12. Long Term Societal Costs of Anterior Discectomy and Fusion (ACDF) versus Cervical Disc Arthroplasty (CDA) for Treatment of Cervical Radiculopathy

    PubMed Central

    Ghori, Ahmer; Konopka, Joseph F.; Cha, Thomas D.; Bono, Christopher M.

    2016-01-01

    Background Current literature suggests that anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) have comparable clinical outcomes for the treatment of cervical radiculopathy. Given similar outcomes, an understanding of differences in long-term societal costs can help guide resource utilization. The purpose of this study was to compare the relative long-term societal costs of anterior cervical discectomy and fusion (ACDF) to cervical disc arthroplasty (CDA) for the treatment of single level cervical disc disease by considering upfront surgical costs, lost productivity, and risk of subsequent revision surgery. Methods We completed an economic and decision analysis using a Markov model to evaluate the long-term societal costs of ACDF and CDA in a theoretical cohort of 45-65 year old patients with single level cervical disc disease who have failed nonoperative treatment. Results The long-term societal costs for a 45-year old patient undergoing ACDF are $31,178 while long-term costs for CDA are $24,119. Long-term costs for CDA remain less expensive throughout the modeled age range of 45 to 65 years old. Sensitivity analysis demonstrated that CDA remains less expensive than ACDF as long as annual reoperation rate remains below 10.5% annually. Conclusions Based on current data, CDA has lower long-term societal costs than ACDF for patients 45-65 years old by a substantial margin. Given reported reoperation rates of 2.5% for CDA, it is the preferred treatment for cervical radiculopathy from an economic perspective. PMID:26913221

  13. Enhancing cell migration in shape-memory alginate-collagen composite scaffolds: In vitro and ex vivo assessment for intervertebral disc repair.

    PubMed

    Guillaume, Olivier; Naqvi, Syeda Masooma; Lennon, Kerri; Buckley, Conor Timothy

    2015-04-01

    Lower lumbar disc disorders pose a significant problem in an aging society with substantial socioeconomic consequences. Both inner tissue (nucleus pulposus) and outer tissue (annulus fibrosus) of the intervertebral disc are affected by such debilitating disorders and can lead to disc herniation and lower back pain. In this study, we developed an alginate-collagen composite porous scaffold with shape-memory properties to fill defects occurring in annulus fibrosus tissue of degenerated intervertebral discs, which has the potential to be administered using minimal invasive surgery. In the first part of this work, we assessed how collagen incorporation on preformed alginate scaffolds influences the physical properties of the final composite scaffold. We also evaluated the ability of annulus fibrosus cells to attach, migrate, and proliferate on the composite alginate-collagen scaffolds compared to control scaffolds (alginate only). In vitro experiments, performed in intervertebral disc-like microenvironmental conditions (low glucose and low oxygen concentrations), revealed that for alginate only scaffolds, annulus fibrosus cells agglomerated in clusters with limited infiltration and migration capacity. In comparison, for alginate-collagen scaffolds, annulus fibrosus cells readily attached and colonized constructs, while preserving their typical fibroblastic-like cell morphology with spreading behavior and intense cytoskeleton expression. In a second part of this study, we investigated the effects of alginate-collagen scaffold when seeded with bone marrow derived mesenchymal stem cells. In vitro, we observed that alginate-collagen porous scaffolds supported cell proliferation and extracellular matrix deposition (collagen type I), with secretion amplified by the local release of transforming growth factor-β3. In addition, when cultured in ex vivo organ defect model, alginate-collagen scaffolds maintained viability of transplanted mesenchymal stem cells for up to 5

  14. Remedy for fictive negative pressures in biphasic finite element models of the intervertebral disc during unloading.

    PubMed

    Schmidt, Hendrik; Galbusera, Fabio; Wilke, Hans-Joachim; Shirazi-Adl, Aboulfazl

    2011-03-01

    Previous biphasic finite element studies investigated the temporal response of a spinal segment under rather simplified loading conditions with no attention to unloading and recovery phases. Employment of existing constitutive relations in porous media yields rather large suction-type pore pressures in the disc as the load suddenly disappears. Such negative pressures are absent in vivo and are hence fictive. The aim of this study was to search for remedies to avoid the computation of negative pressures upon unloading. Partial saturation for the disc or a rest load (RL) higher than 400 N totally eliminated the negative pressures. Decreasing the voids ratio (VR) also led to a reduced negative pressure. When defining a partial saturated disc or using a lower VR in combination with a boundary pressure of 0.25 MPa and a RL of 350 N, no negative pressure was calculated. It appears that the constraint of full saturation and a high mobile fluid fraction of the disc tissues along with inadequate tissue properties are the likely causes of negative pressures during unloading.

  15. Simulated-physiological loading conditions preserve biological and mechanical properties of caprine lumbar intervertebral discs in ex vivo culture.

    PubMed

    Paul, Cornelis P L; Zuiderbaan, Hendrik A; Zandieh Doulabi, Behrouz; van der Veen, Albert J; van de Ven, Peter M; Smit, Theo H; Helder, Marco N; van Royen, Barend J; Mullender, Margriet G

    2012-01-01

    Low-back pain (LBP) is a common medical complaint and associated with high societal costs. Degeneration of the intervertebral disc (IVD) is assumed to be an important causal factor of LBP. IVDs are continuously mechanically loaded and both positive and negative effects have been attributed to different loading conditions.In order to study mechanical loading effects, degeneration-associated processes and/or potential regenerative therapies in IVDs, it is imperative to maintain the IVDs' structural integrity. While in vivo models provide comprehensive insight in IVD biology, an accompanying organ culture model can focus on a single factor, such as loading and may serve as a prescreening model to reduce life animal testing. In the current study we examined the feasibility of organ culture of caprine lumbar discs, with the hypothesis that a simulated-physiological load will optimally preserve IVD properties.Lumbar caprine IVDs (n = 175) were cultured in a bioreactor up to 21 days either without load, low dynamic load (LDL), or with simulated-physiological load (SPL). IVD stiffness was calculated from measurements of IVD loading and displacement. IVD nucleus, inner- and outer annulus were assessed for cell viability, cell density and gene expression. The extracellular matrix (ECM) was analyzed for water, glycosaminoglycan and total collagen content.IVD biomechanical properties did not change significantly with loading conditions. With SPL, cell viability, cell density and gene expression were preserved up to 21 days. Both unloaded and LDL resulted in decreased cell viability, cell density and significant changes in gene expression, yet no differences in ECM content were observed in any group.In conclusion, simulated-physiological loading preserved the native properties of caprine IVDs during a 21-day culture period. The characterization of caprine IVD response to culture in the LDCS under SPL conditions paves the way for controlled analysis of degeneration- and

  16. The three-dimensional architecture of the notochordal nucleus pulposus: novel observations on cell structures in the canine intervertebral disc.

    PubMed

    Hunter, Christopher J; Matyas, John R; Duncan, Neil A

    2003-03-01

    Cells from the nucleus pulposus of young (< 2 years) and old (> 5 years) non-chondrodystrophoid dogs were studied using routine histology, confocal laser scanning microscopy and transmission electron microscopy. The architecture of cell structures--from the tissue scale down to subcellular scale--was reported. Clusters of notochordal cells were observed in young nuclei pulposi, ranging from 10 to 426 cells each. These clusters resisted mechanical disruption and showed evidence of cell-cell signalling via gap junctions. Cells (30-40 microm in diameter) within the clusters had a physaliferous appearance, containing numerous large inclusions which ranged from 1 to 20 microm in diameter. The inclusions were surrounded by a dense actin cortex but were not contained by a lipid bilayer. The contents of the inclusions were determined not to be predominantly carbohydrate or neutral lipid as assessed by histochemical staining, but the exact composition of the contents remained uncertain. There were striking differences in the cell architecture of young vs. old nuclei pulposi, with a loss of both cell clusters and physaliferous cells during ageing. These observations demonstrate unique cell structures, which may influence our understanding of the differences between notochordal and chondrocytic cells in the nucleus pulposus. Such differences could have substantial impact upon how we think about development, degeneration and repair of the intervertebral disc.

  17. Genetic polymorphisms of interleukin-1 alpha and the vitamin d receptor in mexican mestizo patients with intervertebral disc degeneration.

    PubMed

    Cervin Serrano, Salvador; González Villareal, Dalia; Aguilar-Medina, Maribel; Romero-Navarro, Jose Guillermo; Romero Quintana, Jose Geovanni; Arámbula Meraz, Eliakym; Osuna Ramírez, Ignacio; Picos-Cárdenas, Veronica; Granados, Julio; Estrada-García, Iris; Sánchez-Schmitz, Guzman; Ramos-Payán, Rosalío

    2014-01-01

    Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population.

  18. Mesenchymal Stem/Stromal Cells seeded on cartilaginous endplates promote Intervertebral Disc Regeneration through Extracellular Matrix Remodeling

    PubMed Central

    Pereira, Catarina Leite; Teixeira, Graciosa Q.; Ribeiro-Machado, Cláudia; Caldeira, Joana; Costa, Madalena; Figueiredo, Francisco; Fernandes, Rui; Aguiar, Paulo; Grad, Sibylle; Barbosa, Mário A.; Gonçalves, Raquel M.

    2016-01-01

    Intervertebral disc (IVD) degeneration is characterized by significant biochemical and histomorphological alterations, such as loss of extracellular matrix (ECM) integrity, by abnormal synthesis of ECM main components, resultant from altered anabolic/catabolic cell activities and cell death. Mesenchymal Stem/Stromal Cell (MSC) migration towards degenerated IVD may represent a viable strategy to promote tissue repair/regeneration. Here, human MSCs (hMSCs) were seeded on top of cartilaginous endplates (CEP) of nucleotomized IVDs of bovine origin and cultured ex vivo up to 3 weeks. hMSCs migrated from CEP towards the lesion area and significantly increased expression of collagen type II and aggrecan in IVD, namely in the nucleus pulposus. Concomitantly, hMSCs stimulated the production of growth factors, promoters of ECM synthesis, such as fibroblast growth factor 6 (FGF-6) and 7 (FGF-7), platelet-derived growth factor receptor (PDGF-R), granulocyte-macrophage colony-stimulating factor (GM-CSF) and insulin-like growth factor 1 receptor (IGF-1sR). Overall, our results demonstrate that CEP can be an alternative route to MSC-based therapies for IVD regeneration through ECM remodeling, thus opening new perspectives on endogenous repair capacity through MSC recruitment. PMID:27652931

  19. Synthesis and characterization of injectable bioadhesive hydrogels for nucleus pulposus replacement and repair of the damaged intervertebral disc.

    PubMed

    Vernengo, J; Fussell, G W; Smith, N G; Lowman, A M

    2010-05-01

    Bioadhesive polymers are natural or synthetic materials that can be used for soft tissue repair. The aim of this investigation was to develop an injectable, bioadhesive hydrogel with the potential to serve as a synthetic replacement for the nucleus pulposus of the intervertebral disc or as an annulus closure material. Branched copolymers of poly(N-isopropylacrylamide) (PNIPAAm) and poly(ethylene glycol) (PEG) were blended with poly(ethylene imine) (PEI). This three component injectable system can form a precipitated gel at physiological temperature due to the phase transition of PNIPAAm. The injection of glutaraldehyde into the gel core will adhere the implant to the surrounding tissues. (1)H NMR results indicated the successful physical incorporation of PEI into the PNIPAAm-PEG network by blending. In addition, the covalent crosslinking between the amine functionalities on the PEI and the aldehyde functionalities on the glutaraldehyde was verified using FTIR difference spectroscopy. Mechanical characterization of these blends showed a significant increase (p < 0.05) in compressive modulus following glutaraldehyde injection. The in vitro bioadhesive force studies with porcine skin showed a significant increase (p < 0.05) in the mean maximum force of detachment for PNIPAAm-PEG/PEI gels when glutaraldehyde was injected into the gel core. The results of this study indicate that the reactivity between amines and aldehyde functionalities can be exploited to impart bioadhesive properties to PNIPAAm-PEG/PEI copolymers.

  20. Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target

    PubMed Central

    Gilbert, Hamish T. J.; Hodson, Nathan; Baird, Pauline; Richardson, Stephen M.; Hoyland, Judith A.

    2016-01-01

    The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration. PMID:27853274

  1. Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs.

    PubMed

    Sawamura, Kazuhide; Ikeda, Takumi; Nagae, Masateru; Okamoto, Shin-ichi; Mikami, Yasuo; Hase, Hitoshi; Ikoma, Kazuya; Yamada, Tetsuya; Sakamoto, Hirotaka; Matsuda, Ken-ichi; Tabata, Yasuhiko; Kawata, Mitsuhiro; Kubo, Toshikazu

    2009-12-01

    We have previously shown that administration of platelet-rich plasma-impregnated gelatin hydrogel microspheres (PRP-GHMs) into a degenerated intervertebral disc (IVD) markedly suppresses progression of IVD degeneration. In the current study, we characterized the in vivo effects of PRP-GHM treatment in a degenerated IVD model in rabbit. On magnetic resonance images, the IVD height was significantly greater after treatment with PRP-GHMs compared with phosphate-buffered saline-impregnated GHMs, PRP without GHMs, and needle puncture only. Water content was also preserved in PRP-GHM-treated IVDs. Consistent with this observation, the mRNA expression of proteoglycan core protein and type II collagen was significantly higher after PRP-GHM treatment compared with other treatment groups. No proliferating cells were found in the nucleus pulposus and inner annulus fibrosus in any groups, but the number of apoptotic cells in the nucleus pulposus after PRP-GHM treatment was significantly lower than that after other treatments. These results provide an improved understanding of the therapeutic effects of PRP-GHM treatment of degenerated IVDs.

  2. von Frey anesthesiometry to assess sensory impairment after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs.

    PubMed

    Song, R B; Basso, D M; da Costa, R C; Fisher, L C; Mo, X; Moore, S A

    2016-03-01

    Sensory threshold (ST) was measured using an electric von Frey anesthesiometer (VFA) in all limbs of 20 normal dogs and 29 dogs with acute thoracolumbar spinal cord injury (SCI) caused by spontaneous intervertebral disc extrusion. ST values were measured at three separate time points in normal dogs and on days 3, 10 and 30 following decompressive surgery in dogs with SCI. ST values were compared between groups and correlated with locomotor recovery in SCI-affected dogs. ST values were significantly higher (consistent with hypoalgesia) in the pelvic limbs of SCI-affected dogs at day 3, day 10 and day 30 when compared to normal dogs (P <0.05), while no significant difference in thoracic limb ST values was observed between groups. A progressive decrease in pelvic limb ST values occurred in SCI-affected dogs over time, consistent with improvement toward normal sensation or development of allodynia. This finding correlated inversely with locomotor score at 3 and 10 days after surgery. A significant decline in ST values across testing sessions was observed for all limbs of normal and SCI-affected dogs and may be related to patient acclimation, operator training effect, or effect of analgesic medications. This study supports the feasibility of VFA to assess differences in ST between normal and SCI-affected dogs. However, future studies must focus on techniques to minimize or compensate for clinical, environmental and behavioral factors which may impact ST values in the clinical setting.

  3. Suppression of adverse angiogenesis in an albumin-based hydrogel for articular cartilage and intervertebral disc regeneration.

    PubMed

    Scholz, B; Kinzelmann, C; Benz, K; Mollenhauer, J; Wurst, H; Schlosshauer, B

    2010-07-13

    An injectable polyethylene glycol-crosslinked albumin gel (AG) supplemented with hyaluronic acid as a matrix for autologous chondrocyte implantation was evaluated with regard to its impact on angiogenesis. Healthy articular cartilage and intervertebral discs (IVD) are devoid of blood vessels, whereas pathological blood vessel formation augments degeneration of both theses tissues. In contrast to human endothelial cells, primary human articular chondrocytes encapsulated in the AG retained their viability. Endothelial cells did not adhere to the gel surface to a significant extent nor did they proliferate in vitro. The AG did not release any diffusible toxic components. Contrary to Matrigel employed as positive control, the AG prevented endothelial chemoinvasion in Transwell filter assays even in the presence of a chemotactic gradient of vascular endothelial growth factor. In ovo, the AG exhibited a barrier function for blood vessels of the chick chorioallantoic membrane. Subcutaneous implantation of human IVD chondrocytes enclosed in the albumin gel into immunodeficient mice revealed a complete lack of angiogenesis inside the gel after two weeks. At the same time, the IVD chondrocytes within the gel remained vital and displayed a characteristic gene expression pattern as judged from aggrecan, collagen type I and type II mRNA levels. In summary, aiming at articular cartilage and IVD regeneration the albumin gel promises to be a beneficial implant matrix for chondrocytes simultaneously exhibiting non-permissive properties for adverse endothelial cells.

  4. Genetic Polymorphisms of Interleukin-1 Alpha and the Vitamin D Receptor in Mexican Mestizo Patients with Intervertebral Disc Degeneration

    PubMed Central

    Cervin Serrano, Salvador; González Villareal, Dalia; Aguilar-Medina, Maribel; Romero-Navarro, Jose Guillermo; Romero Quintana, Jose Geovanni; Arámbula Meraz, Eliakym; Osuna Ramírez, Ignacio; Picos-Cárdenas, Veronica; Granados, Julio; Estrada-García, Iris; Sánchez-Schmitz, Guzman; Ramos-Payán, Rosalío

    2014-01-01

    Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population. PMID:25506053

  5. The effect of sling exercise on sagittal lumbosacral angle and intervertebral disc area of chronic low back pain patients

    PubMed Central

    Lee, Seung-Bum; Cho, Won-Je

    2016-01-01

    The purpose of this study was to observe the change of lumbosacral angle and intervertebral disc (IVD) area. The study was conducted on chronic low back pain (CLBP) female patients for 12 weeks by operating sling exercise and general physical therapy. The 57 CLBP were divided into 2 groups which, sling exercise group (SEG, n=34) and general physical therapy group (PTG, n=23). The experiment was conducted three times a week for 12 weeks. The lumbosacral angle, which means the angle between the L1–L2 lumbar was measured by plain radiography. The IVD area, which means the IVD height and volume was measured by magnetic resonance imaging. The pain was measured by visual analogue scale (VAS). As a result, after 12-week exercise, VAS had decreased in all groups. The angle of L3–4 and L4–5 and the height of IVD had increased in SEG. Also, IVD height and volume has more improved in SEG compare the PTG. Therefore, the sling exercise is proper treatment for CLBP patients’ recovery because It improve the lumbosacral angle and IVD area. PMID:27807527

  6. Plasma disc decompression for contained cervical disc herniation: a randomized, controlled trial

    PubMed Central

    Nardi, Pier Vittorio

    2009-01-01

    Prospective case series studies have shown that plasma disc decompression (PDD) using the COBLATION SpineWand device (ArthroCare Corporation, Austin, TX) is effective for decompressing the disc nucleus in symptomatic contained cervical disc herniations. This prospective, randomized controlled clinical trial was conducted to evaluate the clinical outcomes of percutaneous PDD as compared to conservative care (CC) through 1 year. Patients (n = 115) had neck/arm pain >50 on the visual analog scale (VAS) pain scale and had failed at least 30 days of failed CC. Patients were randomly assigned to receive either PDD (n = 62) or CC (n = 58). Clinical outcome was determined by VAS pain score, neck disability index (NDI) score, and SF-36 health survey, collected at 6 weeks, 3 months, 6 months, and 1 year. The PDD group had significantly lower VAS pain scores at all follow-up time points (PDD vs. CC: 6 weeks, −46.87 ± 2.71 vs. −15.26 ± 1.97; 3 months, −53.16 ± 2.74 vs. −30.45 ± 2.59; 6 months, −56.22 ± 2.63 vs. −40.26 ± 2.56; 1 year, −65.73 ± 2.24 vs. −36.45 ± 2.86; GEE, P < 0.0001). PDD patients also had significant NDI score improvement over baseline when compared to CC patients at the 6 weeks (PDD vs. CC: −9.15 ± 1.06 vs. −4.61 ± 0.53, P < 0.0001) and 1 year (PDD vs. CC: −16.70 ± 0.29 vs. −12.40 ± 1.26, P = 0.005) follow-ups. PDD patients showed statistically significant improvement over baseline in SF-36 physical component summary scores when compared to CC patients at 6 weeks and 1 year (PDD vs. CC: 8.86 + 8.04 vs. 4.24 ± 3.79, P = 0.0004; 17.64 ± 10.37 vs. 10.50 ± 10.6, P = 0.0003, respectively). In patients who had neck/arm pain due to a contained cervical disc herniation, PDD was associated with significantly better clinical outcomes than a CC regimen. At 1 year, CC patients appeared to suffer a “relapse, showing signs of decline in most measurements, whereas PDD

  7. Chiari malformation, cervical disc prolapse and syringomyelia--always think twice.

    PubMed

    Ball, Jonathon R; Little, Nicholas S

    2008-04-01

    We present the case of a 36-year-old man with neck pain and parasthesia of both upper limbs. Magnetic resonance imaging demonstrated a cervical disc protrusion with spinal cord compression, a Chiari I malformation and cervical syringomyelia. On clinical grounds it was suspected that the cervical stenosis was the symptomatic pathology and an anterior cervical decompression was performed, followed by arthroplasty. Post-operative imaging demonstrated adequate canal decompression, preserved cervical mobility and near-complete resolution of the syrinx. Syringomyelia has a multitude of causes and synchronous pathology can occur. Cervical spondylosis is infrequently associated with syringomyelia. Chiari I malformations are increasingly incidentally detected and asymptomatic. This first report of arthroplasty for cervical spondylosis associated with syringomyelia adds to the growing body of experience with this new technology.

  8. Degeneration of the intervertebral disc with new approaches for treating low back pain.

    PubMed

    Le Maitre, C L; Binch, A L; Thorpe, A A; Hughes, S P

    2015-03-01

    This review paper discusses the process of disc degeneration and the current understanding of cellular degradation in patients who present with low back pain. The role of surgical treatment for low back pain is analysed with emphasis on the proven value of spinal fusion. The interesting and novel developments of stem cell research in the treatment of low back pain are presented with special emphasis on the importance of the cartilaginous end plate and the role of IL-1 in future treatment modalities.

  9. Cell-based therapies for intervertebral disc and cartilage regeneration- Current concepts, parallels, and perspectives.

    PubMed

    Vedicherla, Srujana; Buckley, Conor T

    2017-01-01

    Lower back pain from degenerative disc disease represents a global health burden, and presents a prominent opportunity for regenerative therapeutics. While current regenerative therapies such as autologous disc chondrocyte transplantation (ADCT), allogeneic juvenile chondrocyte implantation (NuQu®), and immunoselected allogeneic adipose derived precursor cells (Mesoblast) show exciting clinical potential, limitations remain. The heterogeneity of preclinical approaches and the paucity of clinical guidance have limited translational outcomes in disc repair, lagging almost a decade behind cartilage repair. Advances in cartilage repair have evolved to single step approaches with improved orthopedic repair and regeneration. Elements from cartilage regeneration endeavors could be adopted and applied to harness translatable approaches and deliver a clinically and economically feasible regenerative surgery for back pain. In this article, we trace the developments behind the translational success of cartilage repair, examine elements to consider in achieving disc regeneration, and the need for surgical redesign. We further discuss clinical parameters, objectives, and coordination required to deliver improved regenerative surgery. Cell source, processing, and delivery modalities are key issues to be addressed in considering surgical redesign. Advances in biomanufacturing, tissue cryobanking, and point of care cell processing technology may enable intraoperative solutions for single step procedures. To maximize translational success a triad partnership between clinicians, industry, and researchers will be critical in providing instructive clinical guidelines for design as well as practical and economic considerations. This will allow a consensus in research ventures and add regenerative surgery into the algorithm in managing and treating a debilitating condition such as back pain. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35

  10. Temporal Analyses of the Response of Intervertebral Disc Cells and Mesenchymal Stem Cells to Nutrient Deprivation

    PubMed Central

    Turner, Sarah A.; Wright, Karina T.; Jones, Philip N.; Balain, Birender; Roberts, Sally

    2016-01-01

    Much emphasis has been placed recently on the repair of degenerate discs using implanted cells, such as disc cells or bone marrow derived mesenchymal stem cells (MSCs). This study examines the temporal response of bovine and human nucleus pulposus (NP) cells and MSCs cultured in monolayer following exposure to altered levels of glucose (0, 3.15, and 4.5 g/L) and foetal bovine serum (0, 10, and 20%) using an automated time-lapse imaging system. NP cells were also exposed to the cell death inducers, hydrogen peroxide and staurosporine, in comparison to serum starvation. We have demonstrated that human NP cells show an initial “shock” response to reduced nutrition (glucose). However, as time progresses, NP cells supplemented with serum recover with minimal evidence of cell death. Human NP cells show no evidence of proliferation in response to nutrient supplementation, whereas MSCs showed greater response to increased nutrition. When specifically inducing NP cell death with hydrogen peroxide and staurosporine, as expected, the cell number declined. These results support the concept that implanted NP cells or MSCs may be capable of survival in the nutrient-poor environment of the degenerate human disc, which has important clinical implications for the development of IVD cell therapies. PMID:26977156

  11. One stage laminoplasty and posterior herniotomy for the treatment of myelopathy caused by cervical stenosis with cervical disc herniation

    PubMed Central

    Yue, Bin; Chen, Bohua; Ma, Xue-Xiao; Xi, Yong-Ming; Xiang, Hong-Fei; Hu, You-Gu; Zhang, Guoqing

    2015-01-01

    The aim of the study was to introduce a method of one stage laminoplasty and posterior herniotomy for myelopathy caused by cervical stenosis with cervical disc herniation and to evaluate the clinical efficacy of this surgery. From 1999 to 2008, 18 patients with myelopathy caused by cervical stenosis with cervical disc herniation who underwent this procedure were included. The average age was 63 years (range 48-74 years), and the average follow-up period was 46 months (range 3-108 months). Neurologic status was evaluated using the JOA scoring system. Neurological symptoms improvement was seen in all patients after surgery. The average JOA score was 14.22±1.86 by final follow-up, which was higher than preoperative values (P<0.01), and the average improvement in neurological function was 76.63%. Neurologic examination showed that excellent results had been obtained by 10 patients, good results by 8 patients, with no fair or poor results. 2 patients developed cerebrospinal fluid leakage after surgery and recovered during the follow-up period. One patient with cervical disc herniation developed postoperative C5 palsy on the axle side on the third day after surgery. She completely recovered by 1 month after surgery. No other patients experienced postoperative neurologic complications. Complete anterior and posterior decompression of the spinal cord was achieved after surgery. We concluded that one stage laminoplasty and posterior herniotomy is an effective, reliable, and safe procedure for the treatment of myelopathy caused by cervical stenosis with cervical disc herniation. PMID:26309625

  12. Clinical and radiographic features of hybrid surgery for the treatment of skip-level cervical degenerative disc disease: A minimum 24-month follow-up.

    PubMed

    Wu, Ting-Kui; Wang, Bei-Yu; Cheng, Ding; Rong, Xin; Lou, Ji-Gang; Hong, Ying; Liu, Hao

    2017-02-25

    We describe the radiographic changes of IS and investigate the safety and feasibility of hybrid surgery (HS) coupling cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) for the treatment of skip-level cervical degenerative disc disease (CDDD). Twenty-seven patients who received HS were retrospectively reviewed. Clinical evaluation based on the Japanese Orthopedic Association (JOA) and Neck Disability Index (NDI) and Visual Analog Scale (VAS) scores. Radiographic parameters included cervical alignment (CA), functional spine unite (FSU) angle of intermediated segment (IS), range of motion (ROM) and intervertebral disc height (IDH). Data regarding radiographic changes at IS were collected. The mean follow-up duration of 30.10months. Compared with preoperative value, JOA, NDI and VAS scores significantly improved after surgery (p<0.05). The CA was recovered significantly after surgery (p<0.05). There was no significant difference in the FSU angle and the IDH of IS between before and at 24months postoperatively (p>0.05). The ROM of IS significantly decreased at the first week after surgery (p<0.05), was similar to preoperative value at 3months postoperatively and significantly increased after 6months (p<0.05). Radiographic changes at IS were observed in 2 patients and Class II Heterotopic ossification (HO) was detected in 2 patients. HS is a safe and feasible alternative procedure for the treatment of skip-level CDDD. It preserved the IS intact and achieved satisfactory clinical and radiographic outcomes over a 24-month follow-up.

  13. Artificial disc and vertebra system: a novel motion preservation device for cervical spinal disease after vertebral corpectomy

    PubMed Central

    Dong, Jun; Lu, Meng; Lu, Teng; Liang, Baobao; Xu, Junkui; Qin, Jie; Cai, Xuan; Huang, Sihua; Wang, Dong; Li, Haopeng; He, Xijing

    2015-01-01

    OBJECTIVE: To determine the range of motion and stability of the human cadaveric cervical spine after the implantation of a novel artificial disc and vertebra system by comparing an intact group and a fusion group. METHODS: Biomechanical tests were conducted on 18 human cadaveric cervical specimens. The range of motion and the stability index range of motion were measured to study the function and stability of the artificial disc and vertebra system of the intact group compared with the fusion group. RESULTS: In all cases, the artificial disc and vertebra system maintained intervertebral motion and reestablished vertebral height at the operative level. After its implantation, there was no significant difference in the range of motion (ROM) of C3–7 in all directions in the non-fusion group compared with the intact group (p>0.05), but significant differences were detected in flexion, extension and axial rotation compared with the fusion group (p<0.05). The ROM of adjacent segments (C3−4, C6−7) of the non-fusion group decreased significantly in some directions compared with the fusion group (p<0.05). Significant differences in the C4-6 ROM in some directions were detected between the non-fusion group and the intact group. In the fusion group, the C4−6 ROM in all directions decreased significantly compared with the intact and non-fusion groups (p<0.01). The stability index ROM (SI-ROM) of some directions was negative in the non-fusion group, and a significant difference in SI-ROM was only found in the C4−6 segment of the non-fusion group compared with the fusion group. CONCLUSION: An artificial disc and vertebra system could restore vertebral height and preserve the dynamic function of the surgical area and could theoretically reduce the risk of adjacent segment degeneration compared with the anterior fusion procedure. However, our results should be considered with caution because of the low power of the study. The use of a larger sample should be considered

  14. Occupational Impact of Multilevel Cervical Disease Treated With Hybrid Cervical Disc Arthroplasty in Active Duty Military Population.

    PubMed

    Cleveland, Andrew; Herzog, Josh; Caram, Pedro

    2016-01-01

    This article evaluates the techniques, results, and complications of hybrid cervical disc arthroplasty in a high-demand military population. Emphasis is on the occupational impact and return to duty outcomes. This article is a case series with prospective follow-up of 30 hybrid cervical disc arthroplasty patients from the authors' institution. Average follow-up was 16.1 months. Average patient age was 39.7 years. Noncommissioned officer was the most common military rank. Cervical disc arthroplasty at C5/6 with fusion at C6/7 was the most common procedure (21/30). All classifications of military occupational specialty were represented. A total of 24/30 (80%) patients returned to duty (RTD) and 24/24 (100%) of RTD patients reported relief (postoperative improvement) compared with 4/6 (66.7%) medical evaluation board patients. Average RTD time was 15.6 weeks. All RTD patients maintained their preoperative military occupational specialty. Hybrid cervical disc arthroplasty has the potential to provide relief and return military patients to preoperative active duty status.

  15. Constitutive expression of cathepsin K in the human intervertebral disc: new insight into disc extracellular matrix remodeling via cathepsin K and receptor activator of nuclear factor-κB ligand

    PubMed Central

    2011-01-01

    Introduction Cathepsin K is a recently discovered cysteine protease which cleaves the triple helical domains of type I to II collagen. It has been shown to be up-regulated in synovial tissue from osteoarthritic and rheumatoid patients, and is a component in normal and nonarthritic cartilage, where it increases with aging. Studies on heart valve development have recently shown that receptor activator of nuclear factor-κB ligand (RANKL) acts during valve remodeling to promote cathepsin K expression. Since extracellular matrix remodeling is a critical component of disc structure and biomechanical function, we hypothesized that cathepsin K and RANKL may be present in the human intervertebral disc. Methods Studies were performed following approval of the authors' Human Subjects Institutional Review Board. Six annulus specimens from healthier Thompson grade I to II discs, and 12 specimens from more degenerate grade III to IV discs were utilized in microarray analysis of RANKL and cathepsin K gene expression. Immunohistochemistry was also performed on 15 additional disc specimens to assess the presence of RANKL and cathepsin K. Results Cathepsin K gene expression was significantly greater in more degenerated grade III to IV discs compared to healthier grade I to II discs (P = 0.001). RANKL was also identified with immunohistochemistry and molecular analyses. RANKL gene expression was also significantly greater in more degenerated discs compared to healthier ones (P = 0.0001). A significant linear positive correlation was identified between expression of cathepsin K and RANKL (r2 = 92.2; P < 0.0001). Conclusions Extracellular matrix remodeling is a key element of disc biology. Our use of an appropriate antibody and gene expression studies showed that cathepsin K is indeed present in the human intervertebral disc. Immunolocalization and molecular analyses also confirmed that RANKL is present in the human disc. Expression of RANKL was found to be significantly greater in

  16. Sacral sparing with cauda equina compression from central lumbar intervertebral disc prolapse.

    PubMed Central

    Lafuente, D J; Andrew, J; Joy, A

    1985-01-01

    Sparing of sensation in sacral dermatomes and of sphincter control was found in eight out of fourteen cases of severe cauda equina compression from massive central lumbar disc prolapse. Although the triangular shape of the lumbar spinal canal may be one factor for this it was found from a necropsy model that the increase in linear strain on the stretched roots of the cauda equina is least in the more centrally placed lower sacral roots. It is argued that the lower tension in these roots is determined by Young's Modulus. PMID:4009195

  17. 1990 Volvo Award in experimental studies. The dependence of intervertebral disc mechanical properties on physiologic conditions.

    PubMed

    Keller, T S; Holm, S H; Hansson, T H; Spengler, D M

    1990-08-01

    In vivo creep-recovery and disc pressure measurements were performed on the lumbar spine of immature and mature swine. The creep-recovery measurements were performed using a custom materials testing apparatus designed to apply static or dynamic loads to the spine of anesthetized animals. A series of three separate experiments were performed to assess the effects of: (I) animal death, (II) graded injury to the disc anulus, and (III) respiratory mechanics on the biomechanical response of the porcine L1-L3 vertebral unit (VU). In Experiments I and II, creep rate, modulus, and viscosity parameters were computed using a three-parameter solid rheological analysis of the displacement-time response recorded during the application of a 300-N load. In Experiment III, the effects of respiratory volume and frequency changes on disc pressure were assessed in the unloaded, statically loaded, and immobilized porcine VU. Our results indicated that the adult VU tended to be stiffer, deform or creep more slowly, and had a significantly higher viscosity than the VU of immature pigs. The results of Experiment I demonstrated that the biomechanical response for the VU was significantly altered by the death of the animal; the VU of the living animal (adolescent or mature) was more compliant and deformed at a faster rate than the VU of the same animal after death. Disc injury produced changes in stiffness, viscosity, and creep rate analogous to that of aging, and on the basis of the graded injuries created in this study, it appears that a small defect in the annulus is just as deleterious as removing a large section of anular material. The results of Experiment III indicated that respiration plays an important role in the normal, in vivo mechanical and nutritional behavior of the porcine VU. Altogether, these results demonstrate that, in the absence of normal physiologic conditions, one may not be able to reliably predict the mechanical response of the lumbar spine, and suggest that

  18. Link protein N-terminal peptide binds to bone morphogenetic protein (BMP) type II receptor and drives matrix protein expression in rabbit intervertebral disc cells.

    PubMed

    Wang, Zili; Weitzmann, M Neale; Sangadala, Sreedhara; Hutton, William C; Yoon, S Tim

    2013-09-27

    Intervertebral disc (IVD) degeneration and associated spinal disorders are leading sources of morbidity, and they can be responsible for chronic low back pain. Treatments for degenerative disc diseases continue to be a challenge. Intensive research is now focusing on promoting regeneration of degenerated discs by stimulating production of the disc matrix. Link protein N-terminal peptide (LPP) is a proteolytic fragment of link protein, an important cross-linker and stabilizer of the major structural components of cartilage, aggrecan and hyaluronan. In this study we investigated LPP action in rabbit primary intervertebral disc cells cultured ex vivo in a three-dimensional alginate matrix. Our data reveal that LPP promotes disc matrix production, which was evidenced by increased expression of the chondrocyte-specific transcription factor SOX9 and the extracellular matrix macromolecules aggrecan and collagen II. Using colocalization and pulldown studies we further document a noggin-insensitive direct peptide-protein association between LPP and BMP-RII. This association mediated Smad signaling that converges on BMP genes leading to expression of BMP-4 and BMP-7. Furthermore, through a cell-autonomous loop BMP-4 and BMP-7 intensified Smad1/5 signaling though a feedforward circuit involving BMP-RI, ultimately promoting expression of SOX9 and downstream aggrecan and collagen II genes. Our data define a complex regulatory signaling cascade initiated by LPP and suggest that LPP may be a useful therapeutic substitute for direct BMP administration to treat IVD degeneration and to ameliorate IVD-associated chronic low back pain.

  19. Link Protein N-terminal Peptide Binds to Bone Morphogenetic Protein (BMP) Type II Receptor and Drives Matrix Protein Expression in Rabbit Intervertebral Disc Cells*

    PubMed Central

    Wang, Zili; Weitzmann, M. Neale; Sangadala, Sreedhara; Hutton, William C.; Yoon, S. Tim

    2013-01-01

    Intervertebral disc (IVD) degeneration and associated spinal disorders are leading sources of morbidity, and they can be responsible for chronic low back pain. Treatments for degenerative disc diseases continue to be a challenge. Intensive research is now focusing on promoting regeneration of degenerated discs by stimulating production of the disc matrix. Link protein N-terminal peptide (LPP) is a proteolytic fragment of link protein, an important cross-linker and stabilizer of the major structural components of cartilage, aggrecan and hyaluronan. In this study we investigated LPP action in rabbit primary intervertebral disc cells cultured ex vivo in a three-dimensional alginate matrix. Our data reveal that LPP promotes disc matrix production, which was evidenced by increased expression of the chondrocyte-specific transcription factor SOX9 and the extracellular matrix macromolecules aggrecan and collagen II. Using colocalization and pulldown studies we further document a noggin-insensitive direct peptide-protein association between LPP and BMP-RII. This association mediated Smad signaling that converges on BMP genes leading to expression of BMP-4 and BMP-7. Furthermore, through a cell-autonomous loop BMP-4 and BMP-7 intensified Smad1/5 signaling though a feedforward circuit involving BMP-RI, ultimately promoting expression of SOX9 and downstream aggrecan and collagen II genes. Our data define a complex regulatory signaling cascade initiated by LPP and suggest that LPP may be a useful therapeutic substitute for direct BMP administration to treat IVD degeneration and to ameliorate IVD-associated chronic low back pain. PMID:23940040

  20. Intervertebral Disc Swelling Demonstrated by 3D and Water Content Magnetic Resonance Analyses after a 3-Day Dry Immersion Simulating Microgravity

    PubMed Central

    Treffel, Loïc; Mkhitaryan, Karen; Gellee, Stéphane; Gauquelin-Koch, Guillemette; Gharib, Claude; Blanc, Stéphane; Millet, Catherine

    2016-01-01

    Background: Vertebral deconditioning is commonly experienced after space flight and simulation studies. Disc herniation is quadrupled after space flight. Purpose: The main hypothesis formulated by the authors is that microgravity results in intervertebral disc (IVD) swelling. Study Design: The aim of the study was to identify the morphological changes of the spine and their clinical consequences after simulated microgravity by 3-day dry immersion (DI). The experimental protocol was performed on 12 male volunteers using magnetic resonance imaging and spectroscopy before and after DI. Methods: All the experiment was financially supported by CNES (Centre national d'études spatiales i.e., French Space Agency). Results: We observed an increase in spine height of 1.5 ± 0.4 cm and a decrease in curvature, particularly for the lumbar region with a decrease of −4 ± 2.5°. We found a significant increase in IVD volume of +8 ± 9% at T12-L1 and +11 ± 9% at L5-S1. This phenomenon is likely associated with the increase in disc intervertebral water content (IWC), 17 ± 27%. During the 3 days in DI, 92% of the subjects developed back pain in the lumbar region below the diaphragmatic muscle. This clinical observation may be linked to the morphological changes of the spine. Conclusions: The morphological changes observed and, specifically, the disc swelling caused by increased IWC may contribute to understanding disc herniation after microgravity exposure. Our results confirmed the efficiency of the 3-day DI model to reproduce quickly the effects of microgravity on spine morphology. Our findings raise the question of the subject selection in spatial studies, especially studies about spine morphology and reconditioning programs after space flight. These results may contribute to a better understanding of the mechanisms underlying disc herniation and may serve as the basis to develop countermeasures for astronauts and to prevent IVD herniation and back pain on Earth. PMID

  1. Effects of enzymatic digestion on compressive properties of rat intervertebral discs.

    PubMed

    Barbir, Ana; Michalek, Arthur J; Abbott, Rosalyn D; Iatridis, James C

    2010-04-19

    Enzymatic treatments were applied to rat motion segments to establish structure-function relationships and determine mechanical parameters most sensitive to simulated remodeling and degeneration. Rat caudal and lumbar disc biomechanical behaviors were evaluated to improve knowledge of their similarities and differences due to their frequent use during in vivo models. Caudal motion segments were assigned to four groups: soaked (control), genipin treated, elastase treated, and collagenase treated. Fresh lumbar and caudal discs were also compared. The mechanical protocol involved five force-controlled loading stages: equilibration, cyclic compression-tension, quasi-static compression, frequency sweep, and creep. Crosslinking was found to have the greatest effect on IVD properties at resting stress. Elastin's role was greatest in tension and at higher force conditions, where GAG content was also a contributing factor. Collagenase treatment caused tissue compaction, which impacted mechanical properties at both high and low force conditions. Equilibration creep and cyclic compression-tension tests were the mechanical tests most sensitive to alterations in specific matrix constituents. Caudal and lumbar motion segments had many similarities but biomechanical differences suggested some distinctions in collagenous structure and water transport characteristics in addition to the geometric differences. Results provide a basis for interpreting biomechanical changes observed in animal model studies of degeneration and remodeling, and underscore the need to maintain and/or repair collagen integrity in IVD health and disease.

  2. Finite Element Study of a Lumbar Intervertebral Disc Nucleus Replacement Device.

    PubMed

    Coogan, Jessica S; Francis, W Loren; Eliason, Travis D; Bredbenner, Todd L; Stemper, Brian D; Yoganandan, Narayan; Pintar, Frank A; Nicolella, Daniel P

    2016-01-01

    Nucleus replacement technologies are a minimally invasive alternative to spinal fusion and total disc replacement that have the potential to reduce pain and restore motion for patients with degenerative disc disease. Finite element modeling can be used to determine the biomechanics associated with nucleus replacement technologies. The current study focuses on a new nucleus replacement device designed as a conforming silicone implant with an internal void. A validated finite element model of the human lumbar L3-L4 motion segment was developed and used to investigate the influence of the nucleus replacement device on spine biomechanics. In addition, the effect of device design changes on biomechanics was determined. A 3D, L3-L4 finite element model was constructed from medical imaging data. Models were created with the normal intact nucleus, the nucleus replacement device, and a solid silicone implant. Probabilistic analysis was performed on the normal model to provide quantitative validation metrics. Sensitivity analysis was performed on the silicone Shore A durometer of the device. Models were loaded under axial compression followed by flexion/extension, lateral bending, or axial rotation. Compressive displacement, endplate stresses, reaction moment, and annulus stresses were determined and compared between the different models. The novel nucleus replacement device resulted in similar compressive displacement, endplate stress, and annulus stress and slightly higher reaction moment compared with the normal nucleus. The solid implant resulted in decreased displacement, increased endplate stress, decreased annulus stress, and decreased reaction moment compared with the novel device. With increasing silicone durometer, compressive displacement decreased, endplate stress increased, reaction moment increased, and annulus stress decreased. Finite element analysis was used to show that the novel nucleus replacement device results in similar biomechanics compared with the

  3. Finite Element Study of a Lumbar Intervertebral Disc Nucleus Replacement Device

    PubMed Central

    Coogan, Jessica S.; Francis, W. Loren; Eliason, Travis D.; Bredbenner, Todd L.; Stemper, Brian D.; Yoganandan, Narayan; Pintar, Frank A.; Nicolella, Daniel P.

    2016-01-01

    Nucleus replacement technologies are a minimally invasive alternative to spinal fusion and total disc replacement that have the potential to reduce pain and restore motion for patients with degenerative disc disease. Finite element modeling can be used to determine the biomechanics associated with nucleus replacement technologies. The current study focuses on a new nucleus replacement device designed as a conforming silicone implant with an internal void. A validated finite element model of the human lumbar L3–L4 motion segment was developed and used to investigate the influence of the nucleus replacement device on spine biomechanics. In addition, the effect of device design changes on biomechanics was determined. A 3D, L3–L4 finite element model was constructed from medical imaging data. Models were created with the normal intact nucleus, the nucleus replacement device, and a solid silicone implant. Probabilistic analysis was performed on the normal model to provide quantitative validation metrics. Sensitivity analysis was performed on the silicone Shore A durometer of the device. Models were loaded under axial compression followed by flexion/extension, lateral bending, or axial rotation. Compressive displacement, endplate stresses, reaction moment, and annulus stresses were determined and compared between the different models. The novel nucleus replacement device resulted in similar compressive displacement, endplate stress, and annulus stress and slightly higher reaction moment compared with the normal nucleus. The solid implant resulted in decreased displacement, increased endplate stress, decreased annulus stress, and decreased reaction moment compared with the novel device. With increasing silicone durometer, compressive displacement decreased, endplate stress increased, reaction moment increased, and annulus stress decreased. Finite element analysis was used to show that the novel nucleus replacement device results in similar biomechanics compared with

  4. Professional driving and prolapsed lumbar intervertebral disc diagnosed by magnetic resonance imaging – a case–control study

    PubMed Central

    Palmer, Keith T; Griffin, Michael; Ntani, Georgia; Shambrook, James; McNee, Philip; Sampson, Madeleine; Harris, E Clare; Coggon, David

    2012-01-01

    Objectives The aim of this study was to investigate whether whole-body vibration (WBV) is associated with prolapsed lumbar intervertebral disc (PID) and nerve root entrapment among patients with low-back pain (LBP) undergoing magnetic resonance imaging (MRI). Methods A consecutive series of patients referred for lumbar MRI because of LBP were compared with controls X-rayed for other reasons. Subjects were questioned about occupational activities loading the spine, psychosocial factors, driving, personal characteristics, mental health, and certain beliefs about LBP. Exposure to WBV was assessed by six measures, including weekly duration of professional driving, hours driven at a spell, and current 8-hour daily equivalent root-mean-square acceleration A(8). Cases were sub-classified according to whether or not PID/nerve root entrapment was present. Associations with WBV were examined separately for cases with and without these MRI findings, with adjustment for age, sex, and other potential confounders. Results Altogether, 237 cases and 820 controls were studied, including 183 professional drivers and 176 cases with PID and/or nerve root entrapment. Risks associated with WBV tended to be lower for LBP with PID/nerve root entrapment but somewhat higher for risks of LBP without these abnormalities. However, associations with the six metrics of exposure were all weak and not statistically significant. Neither exposure–response relationships nor increased risk of PID/nerve root entrapment from professional driving or exposure at an A(8) above the European Union daily exposure action level were found. Conclusions WBV may be a cause of LBP but it was not associated with PID or nerve root entrapment in this study. PMID:22249859

  5. Pamidronate Down-regulates Tumor Necrosis Factor-alpha Induced Matrix Metalloproteinases Expression in Human Intervertebral Disc Cells

    PubMed Central

    Kang, Young-Mi; Hong, Seong-Hwan; Yang, Jae-Ho; Oh, Jin-Cheol; Park, Jin-Oh; Lee, Byung Ho; Lee, Sang-Yoon; Kim, Hak-Sun; Lee, Hwan-Mo

    2016-01-01

    Background N-containing bisphosphonates (BPs), such as pamidronate and risedronate, can inhibit osteoclastic function and reduce osteoclast number by inducing apoptotic cell death in osteoclasts. The aim of this study is to demonstrate the effect of pamidronate, second generation nitrogen-containing BPs and to elucidate matrix metallo-proteinases (MMPs) mRNA expression under serum starvation and/or tumor necrosis factor alpha (TNF-α) stimulation on metabolism of intervertebral disc (IVD) cells in vitro. Methods Firstly, to test the effect of pamidronate on IVD cells in vitro, various concentrations (10-12, 10-10, 10-8, and 10-6 M) of pamidronate were administered to IVD cells. Then DNA and proteoglycan synthesis were measured and messenger RNA (mRNA) expressions of type I collagen, type II collagen, and aggrecan were analyzed. Secondly, to elucidate the expression of MMPs mRNA in human IVD cells under the lower serum status, IVD cells were cultivated in full serum or 1% serum. Thirdly, to elucidate the expression of MMPs mRNA in IVD cells under the stimulation of 1% serum and TNF-α (10 ng/mL) In this study, IVD cells were cultivated in three dimensional alginate bead. Results Under the lower serum culture, IVD cells in alginate beads showed upregulation of MMP 2, 3, 9, 13 mRNA. The cells in lower serum and TNF-α also demonstrated upregulation of MMP-2, 3, 9, and 13 mRNA. The cells with various doses of pamidronate and lower serum and TNF-α were reveled partial down-regulation of MMPs. Conclusions Pamidronate, N-containing second generation BPs, was safe in metabolism of IVD in vitro maintaining chondrogenic phenotype and matrix synthesis, and down-regulated TNF-α induced MMPs expression. PMID:27622181

  6. TGFβ regulates Galectin-3 expression through canonical Smad3 signaling pathway in nucleus pulposus cells: implications in intervertebral disc degeneration.

    PubMed

    Tian, Ye; Yuan, Wen; Li, Jun; Wang, Hua; Hunt, Maxwell G; Liu, Chao; Shapiro, Irving M; Risbud, Makarand V

    2016-03-01

    Galectin-3 is highly expressed in notochordal nucleus pulposus (NP) and thought to play important physiological roles; however, regulation of its expression remains largely unexplored. The aim of the study was to investigate if TGFβ regulates Galectin-3 expression in NP cells. TGFβ treatment resulted in decreased Galectin-3 expression. Bioinformatic analysis using JASPAR and MatInspector databases cross-referenced with published ChIP-Seq data showed nine locations of highly probable Smad3 binding in the LGALS3 proximal promoter. In NP cells, TGFβ treatment resulted in decreased activity of reporters harboring several 5' deletions of the proximal Galectin-3 promoter. While transfection of NP cells with constitutively active (CA)-ALK5 resulted in decreased promoter activity, DN-ALK5 blocked the suppressive effect of TGFβ on the promoter. The suppressive effect of Smad3 on the Galectin-3 promoter was confirmed using gain- and loss-of-function studies. Transfection with DN-Smad3 or Smad7 blocked TGFβ mediated suppression of promoter activity. We also measured Galectin-3 promoter activity in Smad3 null and wild type cells. Noteworthy, promoter activity was suppressed by TGFβ only in wild type cells. Likewise, stable silencing of Smad3 in NP cells using sh-Smad3 significantly blocked TGFβ-dependent decrease in Galectin-3 expression. Treatment of human NP cells isolated from tissues with different grades of degeneration showed that Galectin-3 expression was responsive to TGF-β-mediated suppression. Importantly, Galectin-3 synergized effects of TNF-α on inflammatory gene expression by NP cells. Together these studies suggest that TGFβ, through Smad3 controls Galectin-3 expression in NP cells and may have implications in the intervertebral disc degeneration.

  7. Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs.

    PubMed

    Zhu, Jun; Tang, Haoyu; Zhang, Zhenhua; Zhang, Yong; Qiu, Chengfeng; Zhang, Ling; Huang, Pinge; Li, Feng

    2017-02-01

    Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration.

  8. Lumbar intervertebral disc degeneration associated with axial and radiating low back pain in ageing SPARC-null mice.

    PubMed

    Millecamps, Magali; Tajerian, Maral; Naso, Lina; Sage, E Helene; Stone, Laura S

    2012-06-01

    Chronic low back pain (LBP) is a complex, multifactorial disorder with unclear underlying mechanisms. In humans and rodents, decreased expression of secreted protein acidic rich in cysteine (SPARC) is associated with intervertebral disc (IVD) degeneration and signs of LBP. The current study investigates the hypothesis that IVD degeneration is a risk factor for chronic LBP. SPARC-null and age-matched control mice ranging from 6 to 78 weeks of age were evaluated in this study. X-ray and histologic analysis revealed reduced IVD height, increased wedging, and signs of degeneration (bulging and herniation). Cutaneous sensitivity to cold, heat, and mechanical stimuli were used as measures of referred (low back and tail) and radiating pain (hind paw). Region specificity was assessed by measuring icilin- and capsaicin-evoked behaviour after subcutaneous injection into the hind paw or upper lip. Axial discomfort was measured by the tail suspension and grip force assays. Motor impairment was determined by the accelerating rotarod. Physical function was evaluated by voluntary activity after axial strain or during ambulation with forced lateral flexion. SPARC-null mice developed (1) region-specific, age-dependent hypersensitivity to cold, icilin, and capsaicin (hind paw only), (2) axial discomfort, (3) motor impairment, and (4) reduced physical function. Morphine (6 mg/kg, i.p.) reduced cutaneous sensitivity and alleviated axial discomfort in SPARC-null mice. Ageing SPARC-null mice mirror many aspects of the complex and challenging nature of LBP in humans and incorporate both anatomic and functional components of the disease. The current study supports the hypothesis that IVD degeneration is a risk factor for chronic LBP.

  9. [Longterm results of cervical arthroplasty with disc prosthesis. A literature review].

    PubMed

    Fransen, P; Schils, F

    2014-01-01

    Cervical arthroplasty has now been performed for over 10 years. Despite the large number of implanted artificial discs, the quality of the published studies is weak, and very few report a follow up exceeding two years. We reviewed the literature on cervical total disc replacement, focusing on publications reporting a follow-up of more than two years. The selection of patients, the type of implant and the surgical technique seem to influence greatly the quality of the clinical and radiological results. The occurrence of heterotopic ossifications around the implant seems to be the rule rather than the exception. Wear debris are likely to be observed in the vicinity of the prosthesis. Most long term studies also report a progressive decrease in the range of motion of the prosthesis, although without influence on the clinical evolution. It seems reasonable to say that cervical disc prosthesis is not inferior to discectomy and fusion, and that these implants allow a short term preservation of cervical mobility, but the efficacy in preventing adjacent segment disease or a favourable costleffectiveness ratio have yet to be demonstrated. A more widespread use of cervical disc prosthesis can only be suggested when these questions have been answered by long term follow-up studies.

  10. Hybrid Surgery of Multilevel Cervical Degenerative Disc Disease : Review of Literature and Clinical Results

    PubMed Central

    Lee, Sang-Bok; Kim, Jong-Youn; Yoo, Do-Sung; Lee, Tae-Gyu; Huh, Pil-Woo

    2012-01-01

    Objective In the present study, we evaluated the effect, safety and radiological outcomes of cervical hybrid surgery (cervical disc prosthesis replacement at one level, and interbody fusion at the other level) on the multilevel cervical degenerative disc disease (DDD). Methods Fifty-one patients (mean age 46.7 years) with symptomatic multilevel cervical spondylosis were treated using hybrid surgery (HS). Clinical [neck disability index (NDI) and Visual Analogue Scale (VAS) score] and radiologic outcomes [range of motion (ROM) for cervical spine, adjacent segment and arthroplasty level] were evaluated at routine postoperative intervals of 1, 6, 12, 24 months. Review of other similar studies that examined the HS in multilevel cervical DDD was performed. Results Out of 51 patients, 41 patients received 2 level hybrid surgery and 10 patients received 3 level hybrid surgery. The NDI and VAS score were significantly decreased during the follow up periods (p<0.05). The cervical ROM was recovered at 6 and 12 month postoperatively and the mean ROM of inferior adjacent segment was significantly larger than that of superior adjacent segments after surgery. The ROM of the arthoplasty level was preserved well during the follow up periods. No surgical and device related complications were observed. Conclusion Hybrid surgery is a safe and effective alternative to fusion for the management of multilevel cervical spondylosis. PMID:23323165

  11. Effect of Static Load on the Nucleus Pulposus of Rabbit Intervertebral Disc Motion Segment in Ex vivo Organ Culture

    PubMed Central

    Zhu, Li-Guo; Feng, Min-Shan; Zhan, Jia-Wen; Zhang, Ping; Yu, Jie

    2016-01-01

    Background: The development of mechanically active culture systems helps increase the understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures allow for preservation of the native IVD structure, and adjacent vertebral bodies facilitate the application and control of mechanical loads. The purpose of this study was to establish loading and organ culture methods for rabbit IVD motion segments to study the effect of static load on the whole disc organ. Methods: IVD motion segments were harvested from rabbit lumbar spines and cultured in no-loading 6-well plates (control conditions) or custom-made apparatuses under a constant, compressive load (3 kg, 0.5 MPa) for up to 14 days. Tissue integrity, matrix synthesis, and the matrix gene expression profile were assessed after 3, 7, and 14 days of culturing and compared with those of fresh tissues. Results: The results showed that ex vivo culturing of motion segments preserved tissue integrity under no-loading conditions for 14 days whereas the static load gradually destroyed the morphology after 3 days. Proteoglycan contents were decreased under both conditions, with a more obvious decrease under static load, and proteoglycan gene expression was also downregulated. However, under static load, immunohistochemical staining intensity and collagen Type II alpha 1 (COL2A1) gene expression were significantly enhanced (61.54 ± 5.91, P = 0.035) and upregulated (1.195 ± 0.040, P = 0.000), respectively, compared with those in the controls (P < 0.05). In contrast, under constant compression, these trends were reversed. Our initial results indicated that short-term static load stimulated the synthesis of collagen Type II alpha 1; however, sustained constant compression led to progressive degeneration and specifically to a decreased proteoglycan content. Conclusions: A loading and organ culture system for ex vivo rabbit IVD motion segments was developed. Using this system, we

  12. OPG rs2073617 polymorphism is associated with upregulated OPG protein expression and an increased risk of intervertebral disc degeneration

    PubMed Central

    Xue, Jing-Bo; Zhan, Xin-Li; Wang, Wen-Jun; Yan, Yi-Guo; Liu, Chong

    2016-01-01

    The present study aimed to investigate the associations between three distinct osteoprotegerin (OPG) gene polymorphisms and the risk of intervertebral disc degeneration (IDD). A total of 200 IDD patients and 200 healthy controls were recruited from the Department of Spine Surgery at the First Affiliated Hospital of the University of South China (Hengyang, China) between January 2013 and May 2014. The allele, genotype and haplotype frequency distributions of three OPG polymorphisms in the study and control populations were analyzed by polymerase chain reaction prior to restriction fragment length polymorphism or high resolution melting assays. In addition, serum OPG levels were measured via an ELISA. The genotype and allele frequencies of the OPG rs2073617 polymorphisms were significantly higher in the IDD patients, as compared with the control group (P<0.05). Furthermore, carriers of the C allele exhibited a higher risk of IDD, as compared with carriers of the T allele (P<0.001). Conversely, the genotype and allele frequencies of the two other gene polymorphisms, rs2073618 and rs3102735, showed no significant differences between the patients and controls (P>0.05). The serum OPG levels were significantly higher in IDD patients with TT, TC and CC genotypes at the OPG rs2073617 polymorphism, as compared with the control group (P<0.05). Logistic-regression analysis suggested that high serum levels of OPG were positively correlated with IDD risk, whereas the T-C-A, T-G-A and T-G-G haplotypes were negatively correlated with IDD risk (P<0.05). Furthermore, the G-T-G haplotype was associated with protection against IDD (P=0.008), whereas the G-C-G haplotype was associated with an elevated susceptibility to IDD (P=0.007). The results of the present study suggested that OPG rs2073617 polymorphisms and upregulated serum levels of OPG were associated with an increased risk of IDD, whereas the T-C-A, T-G-A and T-G-G haplotypes were protective factors for IDD. The results of the

  13. MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells

    PubMed Central

    Lv, Feng; Huang, Yingzi; Lv, Wentao; Yang, Longbiao; Li, Feng; Fan, Jingli; Sun, Jianmin

    2017-01-01

    Background Intervertebral disc degeneration (IDD) has been widely recognized as a major contributor to low back pain. Accumulating evidence suggests that IDD is linked to various pro-inflammatory cytokines and metabolites. Recently, numerous studies have demonstrated that microRNAs (miRNAs) play a pivotal role in the development of most disorders, including degenerative disc diseases. Previous reports have revealed that miRNA-146a (miR-146a) could attenuate neuropathic pain in the spinal cord. The aim of this study was to investigate the role of miR-146a in the inflammatory response of IDD. Material/Methods Quantitative real-time (RT)-PCR was performed to investigate the levels of miR-146a in the PBMCs (peripheral blood mononuclear cells) of patients with IDD. Human nucleus pulposus (NP) cells were transiently transfected with miR-146a mimic; control NP cell transfections lacked miR-146a. Then all NP cells were treated with LPS (10 μM) to induce inflammation. The mRNA levels of miR-146a in NP cells were determined by RT-PCR. In addition, the mRNA and protein expression levels of tumor necrosis factor (TNF), receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB in NP cells were evaluated by quantitative RT-PCR and Western blot analysis, respectively. Results We found that miR-146a was significantly downregulated in the PBMCs of patients. Moreover, overexpression of miR-146a significantly decreased the levels of pro-inflammatory cytokines in LPS-stimulated NP cells. The mRNA and protein levels of TRAF6 and NF-κB were downregulated by miR-146a overexpression. Conclusions These results suggest that overexpression of miR-146a could promote IDD through the TRAF/NF-κB pathway. Our findings also highlight miR-146a as a novel possible therapeutic target for IDD. PMID:28161709

  14. Utilization trends of cervical artificial disc replacement during the FDA investigational device exemption clinical trials compared to anterior cervical fusion.

    PubMed

    Qureshi, Sheeraz A; Koehler, Steven M; Lu, Young; Cho, Samuel; Hecht, Andrew C

    2013-12-01

    While anterior cervical discectomy and fusion (ACDF) is the gold standard surgical treatment for cervical disc disease, concerns regarding adjacent segment degeneration lead to the development of cervical disc arthroplasty (CDA). This study compares the utilization trends of CDA versus ACDF during the period of the Food and Drug Administration Investigational Device Exemption clinical trials from 2004 to 2007. The Healthcare Cost and Utilization Project Nationwide Inpatient Sample database was used to identify CDA and ACDF procedures performed in the USA between 2004 and 2007. The prevalence of CDA and ACDF procedures was estimated and stratified by age, sex, diagnosis, census region, payor class, and hospital characteristics. The average length of hospital stay, total charges, and costs were also estimated. The number of CDA surgeries significantly increased annually from 2004 to 2007 and mostly took place at urban non-teaching hospitals. There were no regional differences between CDA and ACDF utilization. There was no difference between sex or admission type between CDA and ACDF patients. ACDF patients were older and had more diabetes, hypertension, and chronic obstructive pulmonary disease. CDA patients were more likely to be discharged home and had shorter hospital stays but had a higher rate of deep venous thrombosis than ACDF patients. Significantly more CDA patients had private insurance while more ACDF patients had Medicare. The average cost was higher for ACDF than CDA. While ACDF dominated surgical intervention for cervical disc disease during the trial period, CDA utilization increased at a significantly greater rate suggesting rapid early adoption.

  15. The Association Between Modic Changes of Lumbar Endplates and Spontaneous Absorption of Herniated Intervertebral Discs.

    PubMed

    Ding, Lingzhi; Teng, Xiao; Fan, Shunwu; Zhao, Fengdong

    2015-04-01

    Herniated disc (HD) is one of the most common causes of lower back pain. Treatment for HD includes conservative therapy and surgical intervention. Following conservative treatment, spontaneous absorption of HD occurs in some patients. To assess whether modic changes are associated with spontaneous absorption of HD, 85 patients with or without modic changes were followed up after 6 months of conservative treatment. As result, we found modic changes of lumbar endplates are associated with poor absorption of HD after conservative treatment. In addition, patients with modic changes exhibit significantly increased cartilage content and decreased neovascularization and macrophage infiltration in HD tissues, all of which are known to impair spontaneous absorption of herniated tissues. At molecular level, modic changes are associated with decreased expression of matrix metalloproteinase-3 gene, which is a key matrix-degrading enzyme for tissue absorption. Our study established a strong association between modic changes of lumbar endplates and spontaneous absorption of lumbar HD, which provided a potential novel method for prediction of spontaneous absorption.

  16. A case of cervical metastases in a patient with preexisting cervical disc replacement and fusion after 2-year symptom-free interval: when do we need interdisciplinary diagnostics?

    PubMed

    Melloh, Markus; Barz, Thomas

    2012-08-01

    Recurrent cervical symptoms frequently occur after cervical disc replacement and fusion. To date, no algorithm for the diagnostic assessment of these symptoms has been established. We present a case report and review of the literature to illustrate the need for interdisciplinary diagnostics in recurrent cervicobrachialgia without pathological cervical imaging. The hospital chart, medical history, physical examination, and imaging of a single patient were reviewed. A 53-year-old man with preexisting cervical disc replacement and fusion presented with a new episode of cervicobrachialgia after a 2-year symptom-free interval. Cervical magnetic resonance imaging (MRI) showed no pathological findings. Six months later the patient reported increasing symptoms including numbness and weakness of the right arm. Repeated cervical MRI and thoracic computed tomography revealed cervical metastases with intraspinal tumor growth and an underlying extensive small cell bronchial carcinoma. In recurrent cervicobrachialgia, without pathological cervical imaging, interdisciplinary diagnostics are needed. Basic diagnostic tests may assist to exclude severe non-vertebrogenic pathologies.

  17. New Classification for Clinically Symptomatic Adjacent Segment Pathology in Cervical Disc Disease

    PubMed Central

    2015-01-01

    Study Design Clinical adjacent segment pathology (CASP) is common after cervical disc surgery. A critical examination of 320 patients operated for cervical disc prolapse revealed that CASP can also occur in patients with congenital and degenerative fusion of cervical spine. This has not been studied in depth and there is a need for a practically applicable classification of CASP. Purpose To develop a new classification scheme of CASP. Overview of Literature A review of the literature did not reveal a practically applicable classification incorporating the occurrence of CASP in congenital and degenerative fusion cases. Methods This was a retrospective analysis of 320 patients operated (509 disc spaces) on for cervical disc prolapse. Cases (n=316) were followed-up for 3-11 years. Random sampling of 220 patients with postoperative magnetic resonance imaging (MRI) in 165 cases was analyzed. Results Six symptomatic CASP cases required resurgery (1.9%), eight cases involved MRI proven CASP with axial neck pain only and 13 patients were asymptomatic with radiological adjacent segment pathology (RASP). The frequency rate was 8.5% (27/316). Four cases of congenital or degenerative fusion of vertebra developed CASP requiring surgery. CASP is classified as primary or secondary follows. Primary A1 was congenital fusion of vertebra and primary A2 was degenerative fusion of the vertebra. Secondary, which was after cervical disc surgery, comprised B1 (RASP in asymptomatic patients), B2 (CASP in patients with axial neck pain), and B3 (CASP with myeloradiculopathy). B3 was subdivided into single-level CASP (B3a) and multiple-level CASP (B3b). Conclusions Symptomatic CASP requiring resurgery is infrequent. CASP can occur in patients with congenital and degenerative fusion of the cervical spine. A new classification for CASP along with treatment strategy is proposed. Patients in Primary CASP and B3 CASP require resurgery while others require only observation. PMID:26712514

  18. Surgical management of high cervical disc prolapse associated with basilar invagination--two case reports.

    PubMed

    Goel, Atul; Phalke, Umesh; Cacciola, Francesco; Muzumdar, Dattatraya

    2004-03-01

    C3-4 cervical disc prolapse was associated with basilar invagination and short neck in a 21-year-old man and additionally with an extensive Klippel-Feil abnormality and fusion of multiple cervical vertebrae in a 32-year-old man. The transoral surgical route was adopted for cervical discectomy in the latter case and an additional odontoidectomy in the former case. Interbody plate and screw fixation was carried out in the patient with Klippel-Feil abnormality. Both the patients were relieved of symptoms and remained asymptomatic at follow up. Simultaneous fixation procedure is not mandatory after transoral surgery in patients with basilar invagination.

  19. Short Link N Stimulates Intervertebral Disc Repair in a Novel Long-Term Organ Culture Model that Includes the Bony Vertebrae.

    PubMed

    AlGarni, Nizar; Grant, Michael P; Epure, Laura M; Salem, Omar; Bokhari, Rakan; Antoniou, John; Mwale, Fackson

    2016-11-01

    Link N (DHLSDNYTLDHDRAIH) is a peptide that occurs naturally in the intervertebral discs (IVDs) and cartilage as a result of proteolytic cleavage of Link protein. Several studies have identified Link N as a growth factor capable of stimulating matrix synthesis in these tissues. We have recently discovered that annulus fibrosus cells can release an enzyme (possibly cathepsin K) that can further cleave Link N resulting in an eight amino acid peptide, we called short Link N (sLink N). Separately, we recently developed and validated an organ culture model that has the vertebrae attached (vIVDs; IVD with intact vertebrae). The aims of this study were (i) to examine if sLink N has the potential to repair early degenerate discs and (ii) to determine if this new model can be used to test potential drugs for disc repair. To determine if sLink N was able to stimulate repair of the degenerate disc, vIVDs with trypsin-induced degeneration (DG) were used. After 4 weeks of culture, the proteoglycan content measured as glycosaminoglycans was stimulated by sLink N in the degenerated discs, and the staining of proteoglycan was observed throughout the tissue irrespective of its proximity to the cells. The quantity of extractable type II collagen and aggrecan was also increased when the degenerate discs were treated with sLink N. Taken together, the results suggest that sLink N can increase key disc matrix molecules, namely type II collagen and aggrecan. Thus sLink N is an attractive peptide for tissue engineering and regeneration of the disc due to its anabolic effects. Finally, we show the feasibility of using the long-term whole organ culture system with adjacent intact vertebrae for studying the DG and regeneration of the IVD.

  20. A Prospective Study of the Functional Outcome of Anterior Cervical Discectomy With Fusion in Single Level Degenerative Cervical Disc Prolapse

    PubMed Central

    Kamani, Mayur M; Shetty, Vikram; Rai, H. Ravindranath; Hegde, Deepak

    2016-01-01

    Introduction Cervical spondylotic myelo-radiculopathy is a form of spinal cord dysfunction syndrome and usually accompanies age related degeneration of the spine. Aim To determine the functional outcome of anterior cervical discectomy with fusion and plating in single level degenerative cervical disc prolapse. Materials and Methods A total of 20 patients diagnosed with degenerative single level cervical disc prolapse who presented to the Department of Orthopaedic Surgery, Justice KS Hegde Charitable Hospital, Mangalore from the period of November 2012 to May 2014 were enrolled in the study. Complete clinical and radiological evaluation of the patients was done. A trial of conservative management was tried in all these patients for a period of two months. They were taken up for surgery only when conservative management had failed. Scoring of neck function before the surgery was done as per the Modified Japanese Orthopaedic Association (MJOA) score. All patients underwent anterior cervical discectomy and fusion (ACDF) with tricortical iliac crest bone grafting. Fixation was performed with titanium locking cervical plates. All patients were reviewed at 6 weeks and 6 months postoperatively. Assessment of neck function was done as per the MJOA scoring during all the reviews. Radiographic assessment was also done during all the reviews. The complications noted were documented. The statistical analysis was done using percentages; the arithmetic mean was calculated using SPSS software (version 16.0). Results Amongst the 20 patients included in the study, 1 patient died postoperatively due to oesophageal rupture. of the remaining 19 patients reviewed and followed up, all of them had improvement of symptoms and were reported to be in the ‘mild category’ as per the MJOA score. One patient developed dysphonia, in the immediate postoperative period due to recurrent laryngeal nerve palsy which recovered in a period of three months postoperative. Conclusion Single level

  1. Single-Level Degenerative Cervical Disc Disease and Driving Disability: Results from a Prospective, Randomized Trial

    PubMed Central

    Kelly, Michael P.; Mitchell, M. David; Hacker, Robert J.; Riew, K. Daniel; Sasso, Rick C.

    2013-01-01

    Study Design Post hoc analysis of prospective, randomized trial. Objective To investigate the disability associated with driving and single-level degenerative, cervical disc disease and to investigate the effect of surgery on driving disability. Methods Post hoc analysis of data obtained from three sites participating in a multicenter, randomized, controlled trial comparing cervical disc arthroplasty (TDA) with anterior cervical discectomy and fusion (ACDF). The driving subscale of the Neck Disability Index (NDI) was analyzed for all patients. A dichotomous severity score was created from the NDI. Statistical comparisons were made within and between groups. Results Two-year follow-up was available for 118/135 (87%) patients. One half of the study population (49.6%) reported moderate or severe preoperative driving difficulty. This disability associated with driving was similar among the two groups (ACDF: 2.5 ± 1.1, TDA: 2.6 ± 1.0, p = 0.646). The majority of patients showed improvement, with no or little driving disability, at the sixth postoperative week (ACDF: 75%, TDA: 90%, p = 0.073). At no follow-up point did a difference exist between groups according to the severity index. Conclusions Many patients suffering from radiculopathy or myelopathy from cervical disc disease are limited in their ability to operate an automobile. Following anterior cervical spine surgery, most patients are able to return to comfortable driving at 6 weeks. PMID:24436875

  2. The Natural History and Clinical Syndromes of Degenerative Cervical Spondylosis

    PubMed Central

    Kelly, John C.; Groarke, Patrick J.; Butler, Joseph S.; Poynton, Ashley R.; O'Byrne, John M.

    2012-01-01

    Cervical spondylosis is a broad term which describes the age related chronic disc degeneration, which can also affect the cervical vertebrae, the facet and other joints and their associated soft tissue supports. Evidence of spondylitic change is frequently found in many asymptomatic adults. Radiculopathy is a result of intervertebral foramina narrowing. Narrowing of the spinal canal can result in spinal cord compression, ultimately resulting in cervical spondylosis myelopathy. This review article examines the current literature in relation to the cervical spondylosis and describes the three clinical syndromes of axial neck pain, cervical radiculopathy and cervical myelopathy PMID:22162812

  3. Clinical and radiologic comparison of dynamic cervical implant arthroplasty versus anterior cervical discectomy and fusion for the treatment of cervical degenerative disc disease.

    PubMed

    Li, Zhonghai; Yu, Shunzhi; Zhao, Yantao; Hou, Shuxun; Fu, Qiang; Li, Fengning; Hou, Tiesheng; Zhong, Hongbin

    2014-06-01

    This study compared the clinical and radiological outcomes of dynamic cervical implant (DCI; Scient'x, Villers-Bretonneux, France) arthroplasty versus anterior cervical discectomy and fusion (ACDF) for the treatment of cervical degenerative disc disease. This prospective cohort study enrolled patients with single-level cervical degenerative disc disease who underwent DCI arthroplasty or ACDF between September 2009 and June 2011. Patients were followed up for more than 2years. Clinical evaluation included the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), Neck Disability Index (NDI), Japan Orthopedic Association (JOA) score, and visual analog scale (VAS) scores for neck and arm pain. Radiological assessments included segmental range of motion (ROM), overall ROM (C2-C7), disc height (DHI), and changes in adjacent disc spaces. The VAS, SF-36, JOA, and NDI scores improved significantly after surgery in both the DCI and ACDF groups. The VAS, JOA, and SF-36 scores were not significantly different between the DCI and ACDF groups at the final follow-up. The segmental ROM at the treated level and overall ROM increased significantly after surgery in the DCI group, but the ROM in the adjacent cephalad and caudal segments did not change significantly. The mean DHI at the treated level was significantly restored after surgery in both groups. Five patients (12.8%) in the DCI group showed new signs of adjacent segment degeneration. These results indicate that DCI is an effective, reliable, and safe procedure for the treatment of cervical degenerative disc disease. However, there is no definitive evidence that DCI arthroplasty has better intermediate-term results than ACDF.

  4. The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression.

    PubMed

    Wang, Kun; Song, Yu; Liu, Wei; Wu, Xinghuo; Zhang, Yukun; Li, Shuai; Kang, Liang; Tu, Ji; Zhao, Kangcheng; Hua, Wenbin; Yang, Cao

    2017-03-24

    Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration. However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, that was transcribed in the opposite direction of ADAMTS5. In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation, in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells involving histone deacetylases. In clinical NP tissues, linc-ADAMTS5 and RREB1 were correlated negatively with ADAMTS5 expression. Taken together, these results demonstrate that RREB1 cooperates with noncoding RNA linc-ADAMTS5 to inhibit ADAMTS5 expression, thereby affecting degeneration of the extracellular matrix of the intervertebral disc.

  5. Longitudinal Changes in the Structure and Inflammatory Response of the Intervertebral Disc Due to Stab Injury in a Murine Organ Culture Model

    PubMed Central

    Abraham, Adam C.; Liu, Jennifer W.; Tang, Simon Y.

    2017-01-01

    Despite the significant public health impact of intervertebral disc (IVD) degeneration and low back pain, it remains challenging to investigate the multifactorial molecular mechanisms that drive the degenerative cascade. Organ culture model systems offer the advantage of allowing cells to live and interact with their native extracellular matrix, while simultaneously reducing the amount of biological variation and complexity present at the organismal level. Murine organ cultures in particular also allow the use of widely available genetically modified animals with molecular level reporters that would reveal insights on the degenerative cascade. Here, we utilize an organ culture system of murine lumbar functional spinal units where we are able to maintain the cellular, metabolic, and structural, and mechanical stability of the whole organ over a 21-day period. Furthermore, we describe a novel approach in organ culture by using tissues from animals with an NF-κB-luc reporter in combination with a mechanical injury model, and are able to show that proinflammatory factors and cytokines such as NF-κB and IL-6 produced by IVD cells can be monitored longitudinally during culture in a stab injury model. Taken together, we utilize a murine organ culture system that maintains the cellular and tissue level behavior of the intervertebral disc and apply it to transgenic animals that allow the monitoring of the inflammatory profile of IVDs. This approach could provide important insights on the molecular and metabolic mediators that regulate the homeostasis of the IVD. PMID:27273204

  6. Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK.

    PubMed

    Li, Kang; Li, Yan; Ma, Zhenjiang; Zhao, Jie

    2015-11-01

    As intervertebral disc (IVD) degeneration has been proven to contribute to low back pain (LBP), drug treatment aiming at attenuating IVD degeneration may prove to be benefiical. Crocin, a bioactive component of saffron, has been found to exert anti-inflammatory effects on cartilage. In the present study, the anti-inflammatory and anti-catabolic effects of crocin on rat IVDs were analyzed in vitro and ex vivo. Nucleus pulposus (NP) cells were isolated from the lumbar IVDs of Sprague-Dawley rats. The NP cells were first treated with various concentrations of crocin, and then stimulated with lipopolysaccharide (LPS) to induce inflammation. Subsequently, RT-qPCR and enzyme-linked immunosorbent assay were carried out to measure the expression levels of catabolic enzymes, pro-inflammatory factors and the components of the extracellular matrix (ECM). In addition, western blot analysis was also used to investigate the related signaling pathways. The whole spinal motion segment (vertebra-IVD-vertebra section) of the rats was isolated and cultured in the presence or absence of LPS and crocin for 7 days. The ex vivo effects of crocin on the ECM of the IVD structures were determined by histological and biochemical analysis. In vitro, crocin significantly inhibited the LPS-induced overexpression of catabolic enzymes [matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif (ADAMTS)-4 and ADAMTS‑5], pro-inflammatory factors [interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and inducible nitric oxide synthase (iNOS)] and Toll-like receptor (TLR)‑2 in a concentration-dependent manner. Notably, crocin partly prevented the downregulation of aggrecan and type II collagen (collagen‑II). Moreover, crocin suppressed the LPS-induced activation of the mitogen-activated protein kinase (MAPK) pathway by inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK). Ex vivo experiments

  7. Mechanical behavior of the human lumbar intervertebral disc with polymeric hydrogel nucleus implant: An experimental and finite element study

    NASA Astrophysics Data System (ADS)

    Joshi, Abhijeet Bhaskar

    The origin of the lower back pain is often the degenerated lumbar intervertebral disc (IVD). We are proposing replacement of the degenerated nucleus by a PVA/PVP polymeric hydrogel implant. We hypothesize that a polymeric hydrogel nucleus implant can restore the normal biomechanics of the denucleated IVD by mimicking the natural load transfer phenomenon as in case of the intact IVD. Lumbar IVDs (n = 15) were harvested from human cadavers. In the first part, specimens were tested in four different conditions for compression: Intact, bone in plug, denucleated and Implanted. Hydrogel nucleus implants were chosen to have line-to-line fit in the created nuclear cavity. In the second part, nucleus implant material (modulus) and geometric (height and diameter) parameters were varied and specimens (n = 9) were tested. Nucleus implants with line-to-line fit significantly restored (88%) the compressive stiffness of the denucleated IVD. The synergistic effect between the implant and the intact annulus resulted in the nonlinear increase in implanted IVD stiffness, where Poisson effect of the hydrogel played major role. Nucleus implant parameters were observed to have a significant effect on the compressive stiffness. All implants with modulus in the tested range restored the compressive stiffness. The undersize implants resulted in incomplete restoration while oversize implants resulted in complete restoration compared to the BI condition. Finite element models (FEM) were developed to simulate the actual test conditions and validated against the experimental results for all conditions. The annulus (defined as hyperelastic, isotropic) mainly determined the nonlinear response of the IVD. Validated FEMs predicted 120--3000 kPa as a feasible range for nucleus implant modulus. FEMs also predicted that overdiameter implant would be more effective than overheight implant in terms of stiffness restoration. Underdiameter implants, initially allowed inward deformation of the annulus and

  8. Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK

    PubMed Central

    LI, KANG; LI, YAN; MA, ZHENJIANG; ZHAO, JIE

    2015-01-01

    As intervertebral disc (IVD) degeneration has been proven to contribute to low back pain (LBP), drug treatment aiming at attenuating IVD degeneration may prove to be benefiical. Crocin, a bioactive component of saffron, has been found to exert anti-inflammatory effects on cartilage. In the present study, the anti-inflammatory and anti-catabolic effects of crocin on rat IVDs were analyzed in vitro and ex vivo. Nucleus pulposus (NP) cells were isolated from the lumbar IVDs of Sprague-Dawley rats. The NP cells were first treated with various concentrations of crocin, and then stimulated with lipopolysaccharide (LPS) to induce inflammation. Subsequently, RT-qPCR and enzyme-linked immunosorbent assay were carried out to measure the expression levels of catabolic enzymes, pro-inflammatory factors and the components of the extracellular matrix (ECM). In addition, western blot analysis was also used to investigate the related signaling pathways. The whole spinal motion segment (vertebra-IVD-vertebra section) of the rats was isolated and cultured in the presence or absence of LPS and crocin for 7 days. The ex vivo effects of crocin on the ECM of the IVD structures were determined by histological and biochemical analysis. In vitro, crocin significantly inhibited the LPS-induced overexpression of catabolic enzymes [matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif (ADAMTS)-4 and ADAMTS-5], pro-inflammatory factors [interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and inducible nitric oxide synthase (iNOS)] and Toll-like receptor (TLR)-2 in a concentration-dependent manner. Notably, crocin partly prevented the downregulation of aggrecan and type II collagen (collagen-II). Moreover, crocin suppressed the LPS-induced activation of the mitogen-activated protein kinase (MAPK) pathway by inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK). Ex vivo experiments demonstrated

  9. Cervical Disc Deformation During Flexion–Extension in Asymptomatic Controls and Single-Level Arthrodesis Patients

    PubMed Central

    Anderst, William; Donaldson, William; Lee, Joon; Kang, James

    2016-01-01

    The aim of this study was to characterize cervical disc deformation in asymptomatic subjects and single-level arthrodesis patients during in vivo functional motion. A validated model-based tracking technique determined vertebral motion from biplane radiographs collected during dynamic flexion–extension. Level-dependent differences in disc compression–distraction and shear deformation were identified within the anterior and posterior annulus (PA) and the nucleus of 20 asymptomatic subjects and 15 arthrodesis patients using a mixed-model statistical analysis. In asymptomatic subjects, disc compression and shear deformation per degree of flexion–extension progressively decreased from C23 to C67. The anterior and PA experienced compression–distraction deformation of up to 20%, while the nucleus region was compressed between 0% (C67) and 12% (C23). Peak shear deformation ranged from 16% (at C67) to 33% (at C45). In the C5–C6 arthrodesis group, C45 discs were significantly less compressed than in the control group in all disc regions (all p ≤ 0.026). In the C6–C7 arthrodesis group, C56 discs were significantly less compressed than the control group in the nucleus (p = 0.023) and PA (p = 0.014), but not the anterior annulus (AA; p = 0.137). These results indicate in vivo disc deformation is level-dependent, and single-level anterior arthrodesis alters the compression–distraction deformation in the disc immediately superior to the arthrodesis. PMID:23861160

  10. Injection of human umbilical tissue–derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo

    PubMed Central

    Leckie, Steven K.; Sowa, Gwendolyn A.; Bechara, Bernard P.; Hartman, Robert A.; Coelho, Joao Paulo; Witt, William T.; Dong, Qing D.; Bowman, Brent W.; Bell, Kevin M.; Vo, Nam V.; Kramer, Brian C.; Kang, James D.

    2016-01-01

    Background context Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery. Purpose To determine whether injecting human umbilical tissue–derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD. Design Prospective, randomized, blinded placebo–controlled in vivo study. Patient sample Skeletally mature New Zealand white rabbits. Outcome measures Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology. Methods Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2–L3, L3–L4, and L4–L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4–L5 were analyzed histologically. The L3–L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated. Results Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically

  11. The Mobi-C cervical disc for one-level and two-level cervical disc replacement: a review of the literature

    PubMed Central

    Alvin, Matthew D; Mroz, Thomas E

    2014-01-01

    Background Cervical disc arthroplasty (CDA) is a novel motion-preserving procedure that is an alternative to fusion. The Mobi-C disc prosthesis, one of many Food and Drug Administration (FDA)-approved devices for CDA, is the only FDA-approved prosthesis for two-level CDA. Hence, it may allow for improved outcomes compared with multilevel fusion procedures. Purpose To critically assess the available literature on CDA with the Mobi-C prosthesis, with a focus on two-level CDA. Methods All clinical articles involving the Mobi-C disc prosthesis for CDA through September 1, 2014 were identified on Medline. Any paper that presented Mobi-C CDA clinical results was included. Study design, sample size, length of follow-up, use of statistical analysis, quality of life outcome scores, conflict of interest, and complications were recorded. Results Fifteen studies were included that investigated Mobi-C CDA, only one of which was a level Ib randomized control trial. All studies included showed non-inferiority of one-level Mobi-C CDA to one-level anterior cervical discectomy and fusion (ACDF). Only one study analyzed outcomes of one-level versus two-level Mobi-C CDA, and only one study analyzed two-level Mobi-C CDA versus two-level ACDF. In comparison with other cervical disc prostheses, the Mobi-C prosthesis is associated with higher rates of heterotopic ossification (HO). Studies with conflicts of interest reported lower rates of HO. Adjacent segment degeneration or disease, along with other complications, were not assessed in most studies. Conclusion One-level Mobi-C CDA is non-inferior, but not superior, to one-level ACDF for patients with cervical degenerative disc disease. The Mobi-C CDA procedure is associated with high rates of HO. Two-level Mobi-C CDA may be superior to two-level ACDF. However, insufficient evidence exists, thereby mandating a need for unbiased, well-designed prospective studies with well-defined outcomes in the future. PMID:25473319

  12. The Role of Posterior Longitudinal Ligament in Cervical Disc Replacement: An Ovine Cadaveric Biomechanical Analysis

    PubMed Central

    Yu, Cheng-Cheng; Hao, Ding-Jun; Ma, Yu-Li; Huang, Da-Geng; Li, Hou-Kun; Feng, Hang; Hou, Qian

    2016-01-01

    Background Cervical disc replacement (CDR) has been widely used to restore and maintain mobility and function of the treated and adjacent motion segments. Posterior longitudinal ligament (PLL) resection has been shown to be efficient in anterior cervical decompression and fusion. However, less is known about the biomechanical effect of PLL removal versus preservation in cervical disc arthroplasty. Material/Methods Three motion segments of 24 ovine cervical spines (C2–C5) were evaluated in a robotic spine system with axial compressive loads of 50 N. These cervical spines were divided in three groups according to the following conditions: (1) intact spine, (2) C3/C4 CDR with the Prestige LP prosthesis and PLL preservation, and (3) C3/C4 CDR with the Prestige LP prosthesis and PLL removal. The ranges of motion (ROMs) were recorded and analyzed in each group. Results The C3/C4 ROM in group 3 (CDR with PLL removed) increased significantly in flexion-extension and axial rotation compared with group 1 (intact spine). Moreover, in flexion-extension, the mean total ROM was significantly larger in group 3 than in group 1. All the ROM observed in group 2 (CDR with PLL preserved) did not significantly differ from the ROM observed in group 1. Conclusions Compared with intact spines, CDR with PLL removal partly increased ROM. Moreover, the ROM in CDR with PLL preservation did not significantly differ from the ROM observed in intact spines. The PLL appears to contribute to the balance and stability of the cervical spine and should thus be preserved in cervical disc replacement provided that the posterior longitudinal ligament is not degenerative and the compression can be removed without PLL takedown. PMID:27243444

  13. Electro-acupuncture and Chinese herbs for treatment of cervical intervertebral disk disease in a dog

    PubMed Central

    Matera, Júlia Maria; da Silva, Tatiana Soares; de Campos Fonseca Pinto, Ana Carolina Brandão; Cortopassi, Sílvia Renata Gaido

    2007-01-01

    A non-ambulatory dog with tetraparesis following a pain episode that had evolved over 2 months was submitted for medical treatment and diagnosed with intervertebral disk disease at C3-C4 and dorsal extradural compression at C1-C2 and C3-C4 using myelography and computed tomography. The dog experienced ambulation recovery after 15 days of treatment with only electroacupuncture and Chinese herbal medicine, with marked improvement occurring after only 10 treatments. Six months of follow-up demonstrated that the dog was stable and had no recurrence of symptoms. Therefore, it was concluded that the combination of electroacupuncture and Chinese herbal medicine was responsible for motor rehabilitation. PMID:17322780

  14. Cervical Total Disc Replacement is Superior to Anterior Cervical Decompression and Fusion: A Meta-Analysis of Prospective Randomized Controlled Trials

    PubMed Central

    Zhang, Yujie; Liang, Chengzhen; Tao, Yiqing; Zhou, Xiaopeng; Li, Hao; Li, Fangcai; Chen, Qixin

    2015-01-01

    Background Despite being considered the standard surgical procedure for symptomatic cervical disc disease, anterior cervical decompression and fusion invariably accelerates adjacent segment degeneration. Cervical total disc replacement is a motion-preserving procedure developed as a substitute to fusion. Whether cervical total disc replacement is superior to fusion remains unclear. Methods We comprehensively searched PubMed, EMBASE, Medline, and the Cochrane Library in accordance with the inclusion criteria to identify possible studies. The retrieved results were last updated on December 12, 2014. We classified the studies as short-term and midterm follow-up. Results Nineteen randomized controlled trials involving 4516 cases were identified. Compared with anterior cervical decompression and fusion, cervical total disc replacement had better functional outcomes (neck disability index [NDI], NDI success, neurological success, neck pain scores reported on a numerical rating scale [NRS], visual analog scales scores and overall success), greater segmental motion at the index level, fewer adverse events and fewer secondary surgical procedures at the index and adjacent levels in short-term follow-up (P < 0.05). With midterm follow-up, the cervical total disc replacement group indicated superiority in the NDI, neurological success, pain assessment (NRS), and secondary surgical procedures at the index level (P < 0.05). The Short Form 36 (SF-36) and segmental motion at the adjacent level in the short-term follow-up showed no significant difference between the two procedures, as did the secondary surgical procedure rates at the adjacent level with midterm follow-up (P > 0.05). Conclusions Cervical total disc replacement presented favorable functional outcomes, fewer adverse events, and fewer secondary surgical procedures. The efficacy and safety of cervical total disc replacement are superior to those of fusion. Longer-term, multicenter studies are required for a better

  15. Heterotopic ossification associated with myelopathy following cervical disc prosthesis implantation.

    PubMed

    Wenger, Markus; Markwalder, Thomas-Marc

    2016-04-01

    This case report presents a 37-year-old man with clinical signs of myelopathy almost 9 years after implantation of a Bryan disc prosthesis (Medtronic Sofamor Danek, Memphis, TN, USA) for C5/C6 soft disc herniation. As demonstrated on MRI and CT scan, spinal cord compression was caused by bony spurs due to heterotopic ossification posterior to the still moving prosthesis. The device, as well as the ectopic bone deposits, had to be removed because of myelopathy and its imminent aggravation. Conversion to anterior spondylodesis was performed.

  16. Development of Ultrasound to Measure In-Vivo Dynamic Cervical Spine Intervertebral Disc Mechanics

    DTIC Science & Technology

    2016-01-01

    system was validated ex-vivo using cadaveric C-spines mounted in a servo-hydraulic material testing machine by comparing dynamic US measurement to direct...in certain degree without loss of ultrasound images. Figure 2. Human volunteer performing repetitive jumping task with a geared helmet. Impact to...landing with both feet on force plate while maintaining upright posture for 4 minutes, wearing a helmet to simulate military head gear (Figure 2). The

  17. Development of Ultrasound to Measure In-vivo Dynamic Cervical Spine Intervertebral Disc Mechanics

    DTIC Science & Technology

    2015-01-01

    The capability of dual US to measure C-spine properties in-vivo in simulation environment is currently being tested. Biomechanics finite element(FE...and Integrity -9- 3.3 In-vivo Ultrasound Test in Simulated Environment -12- 3.4 FE Model Validaition and Modification and Simulate Operation...C-spine elastic and viscoelastic properties in-vivo under conditions simulating vibrations over a range of frequencies and amplitudes is currently

  18. Effects of Transplantation of hTIMP1-Expressing Bone Marrow Mesenchymal Stem Cells on the Extracellular Matrix of Degenerative Intervertebral Discs in an in vivo Rabbit Model.

    PubMed

    Yi, Zhou; Guanjun, Tu; Lin, Cong; Zifeng, Pei

    2014-04-08

    Study Design. Prospective, randomized controlled animal study.Objective. To observe ECM changes in degenerative IVD after transplantation of bone marrow mesenchymal stem cells (BMSCs) virally transfected with a construct expressing human tissue inhibitor of metalloproteinase 1 (hTIMP-1), and to discuss the feasibility of using this approach to treat intervertebral disc degeneration (IDD).Summary of Background Data. Intervertebral disc (IVD) degeneration is characterized by decreased cell numbers, bioactivity of the nucleus pulposus (NP), and remodeled extracellular matrix (ECM). Exogenous genes can be targeted into cells to produce inhibition of ECM degradation and increase ECM content in IVDs, and thereby potentially stop or reverse degenerative processes and modify disc structure.Methods. BMSCs were isolated from a pure New-Zealand rabbit and identified by flow cytometry. Transgenic BMSCs were acquired by transfection with a recombinant adenovirus vector carrying the hTIMP-1 gene. Animal models of IDD were established by annulus puncture and then given intra-NP injections according to their random assignment into three groups: (1) a transgenic BMSC transplantation (TgBT) group that received BMSCs transfected with an hTIMP-1-expressing adenovirus vector; (2) a BMSC transplantation (BT) group that received unaltered BMSCs; and (3) a control (PCon) group that received cell-free phosphate-buffered saline. Degree of degeneration was evaluated 12 wks after modeling. ECM content was quantified using immunohistochemistry (IHC) and spectrophotography. Expression of hTIMP-1 was observed via quantitative PCR, western blot, and IHC.Results. Significantly fewer degenerative changes and increased ECM content were observed in the TBT and BT groups compared to PCon animals (P < .05). The TBT group had greater ECM content than did the BT group (P < .05), as well as higher levels of hTIMP-1 mRNA and protein.Conclusions. Transplantation of BMSCs transfected with hTIMP-1 can

  19. IL-21 Is Positively Associated with Intervertebral Disc Degeneration by Interaction with TNF-α Through the JAK-STAT Signaling Pathway.

    PubMed

    Chen, Bin; Liu, Yi; Zhang, YuanQiang; Li, JingKun; Cheng, KaiYuan; Cheng, Lei

    2017-04-01

    This study was conducted in order to investigate the function of IL-21 in intervertebral disc degeneration. The serum concentration of IL-21 in patients with lumbar disc herniation (LDH) was examined by ELISA. Immunohistochemistry and western blot analysis were performed to detect the expression of IL-21, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-7), and tumor necrosis factor alpha (TNF-α) in degenerated intervertebral disc (IVD) tissues of human and rat. Moreover, nucleus pulposus (NP) cells were treated with 0, 10, 100, and 1000 ng/mL of IL-21 cytokine with and without AG490. TNF-α, ADAMTS-7, and matrix metalloproteinases-13 (MMP-13) mRNA expression was determined by RT-PCR. The expression of signal transducers and activators of transcription, STAT-1, STAT-3, and STAT-5b, was detected by western blot. IL-21 concentration level is higher in the degenerated group and positively correlates with the visual analog score (VAS). IL-21, ADAMTS-7, and TNF-α can be detected in the degenerative NP tissues in both human and rat degenerated NP tissues. The mRNA expression of ADAMTS-7, TNF-α, and MMP-13 was enhanced after stimulation with IL-21. Compared to control, STAT-1, STAT-3, and STAT-5b expression was also enhanced after IL-21 treatment, with STAT-3 being the most significantly enhanced; furthermore, expression was significantly reduced after treatment with AG490. The mRNA expression of TNF-α was markedly reduced after treatment with AG490 compared to treatment with IL-21 only. IL-21 is involved in the pathological development of IVD degeneration and IL-21 could aggravate IVD degeneration by stimulating TNF-α through the STAT signaling pathway.

  20. Specimen specific parameter identification of ovine lumbar intervertebral discs: On the influence of fibre-matrix and fibre-fibre shear interactions.

    PubMed

    Reutlinger, Christoph; Bürki, Alexander; Brandejsky, Vaclav; Ebert, Lars; Büchler, Philippe

    2014-02-01

    Numerical models of the intervertebral disc, which address mechanical questions commonly make use of the difference in water content between annulus and nucleus, and thus fluid and solid parts are separated. Despite this simplification, models remain complex due to the anisotropy and nonlinearity of the annulus and regional variations of the collagen fibre density. Additionally, it has been shown that cross-links make a large contribution to the stiffness of the annulus. Because of this complex composite structure, it is difficult to reproduce several sets of experimental data with one single set of material parameters. This study addresses the question to which extent the ultrastructure of the intervertebral disc should be modelled so that its moment-angle behaviour can be adequately described. Therefore, a hyperelastic constitutive law, based on continuum mechanical principles was derived, which does not only consider the anisotropy from the collagen fibres, but also interactions among the fibres and between the fibres and the ground substance. Eight ovine lumbar intervertebral discs were tested on a custom made spinal loading simulator in flexion/extension, lateral bending and axial rotation. Specimen-specific geometrical models were generated using CT images and T2 maps to distinguish between annulus fibrosus and nucleus pulposus. For the identification of the material parameters the annulus fibrosus was described with two scenarios: with and without fibre-matrix and fibre-fibre interactions. Both scenarios showed a similar behaviour on a load displacement level. Comparing model predictions to the experimental data, the mean RMS of all specimens and all load cases was 0.54±0.15° without the interaction and 0.54±0.19° when the fibre-matrix and fibre-fibre interactions were included. However, due to the increased stiffness when cross-links effects were included, this scenario showed more physiological stress-strain relations in uniaxial and biaxial stress

  1. Clinical Case Report of Expansive Laminoplasty for Cervical Myelopathy Due to Both Disc Herniation and Developmental Cervical Spinal Canal Stenosis in Older Adolescents

    PubMed Central

    Zhou, Hua; Sun, Yu; Zhang, Fengshan; Dang, Gengting; Liu, Zhongjun

    2016-01-01

    Abstract Reports on adolescent patients with cervical myelopathy who underwent anterior cervical discectomy and fusion are scarce. However, to our knowledge, no cases of expansive laminoplasty for cervical myelopathy associated with progressive neurological deficit after a series of conservative treatment, caused by both disc herniation and developmental cervical spinal canal stenosis, have been reported. From January 2006 to July 2012, we retrospectively studied 3 patients in late adolescence presenting with cervical myelopathy who underwent expansive unilateral open-door laminoplasty at our hospital. The outcomes after the surgery were evaluated according to the Japanese Orthopedic Association scores. Symptoms presented by these patients were due to both disc herniation and developmental cervical spinal canal stenosis. No major complications occurred after the surgical procedures. The median follow-up time was 66 months (range 36–112 months). The Japanese Orthopedic Association scores after surgery showed a significant increase. Long-term outcomes after surgery were satisfactory according to the evaluation criteria for the Japanese Orthopedic Association scores. However, the ranges of motion of the cervical spine decreased, especially the ranges of motion on flexion after surgery showed a significant decrease. Expansive laminoplasty is helpful for older adolescent patients with cervical myelopathy due to both disc herniation and developmental cervical spinal canal stenosis, presenting with progressive neurological deficit after long conservative treatment. PMID:26937923

  2. A videofluoroscopy-based tracking algorithm for quantifying the time course of human intervertebral displacements.

    PubMed

    Balkovec, Christian; Veldhuis, Jim H; Baird, John W; Brodland, G Wayne; McGill, Stuart M

    2017-03-15

    The motions of individual intervertebral joints can affect spine motion, injury risk, deterioration, pain, treatment strategies, and clinical outcomes. Since standard kinematic methods do not provide precise time-course details about individual vertebrae and intervertebral motions, information that could be useful for scientific advancement and clinical assessment, we developed an iterative template matching algorithm to obtain this data from videofluoroscopy images. To assess the bias of our approach, vertebrae in an intact porcine spine were tracked and compared to the motions of high-contrast markers. To estimate precision under clinical conditions, motions of three human cervical spines were tracked independently ten times and vertebral and intervertebral motions associated with individual trials were compared to corresponding averages. Both tests produced errors in intervertebral angular and shear displacements no greater than 0.4° and 0.055 mm, respectively. When applied to two patient cases, aberrant intervertebral motions in the cervical spine were typically found to correlate with patient-specific anatomical features such as disc height loss and osteophytes. The case studies suggest that intervertebral kinematic time-course data could have value in clinical assessments, lead to broader understanding of how specific anatomical features influence joint motions, and in due course inform clinical treatments.

  3. Stepwise illustration of teeth-fixation semi-constrained cervical disc arthroplasty.

    PubMed

    Chang, Chih-Chang; Wu, Jau-Ching; Chang, Peng-Yuan; Yeh, Mei-Yin; Kuo, Yi-Hsuan; Fay, Li-Yu; Tu, Tsung-Hsi; Huang, Wen-Cheng; Cheng, Henrich

    2017-01-01

    There are many kinds of artificial discs available for cervical disc arthroplasty (CDA), with various designs of fixation and articulation mechanisms. Each of these designs has different features and theoretically fits most optimally in selected types of patients. However, there has been insufficient literature to guide individualized selection among these CDA devices. Since CDA aims to restore the joint function rather than arthrodesis, tailor-made size, shape, and mechanical properties should be taken into account for each candidate's target disc. Despite several large-scale prospective randomized control trials that have demonstrated the effectiveness and durability of CDA for up to 8 years, none of them involved more than one kind of artificial disc. In this video the authors present detailed steps and technical aspects of the newly introduced ProDisc-C Vivo (DePuy Synthes Spine), which has the same ball-and-socket design for controlled, predictable motion as the ProDisc-C. The newly derived teeth fixation provides high primary stability and multilevel capability by avoidance of previous keel-related limitations and complications (e.g., split vertebral fracture). Please note that the ProDisc-C Vivo is currently not available on the US market. The authors present the case of a 53-year-old woman who had symptoms of both radiculopathy and myelopathy caused by a large, calcified disc herniation at C4-5. There was no improvement after 4 months of medical treatment and rehabilitation. A single-level CDA was successfully performed with the ProDisc-C Vivo, and her symptoms were completely ameliorated afterward. The follow-up images demonstrated preservation of motion at the indexed level. The video can be found here: https://youtu.be/4DSES1xgvQU .

  4. [Infarction of the spinal cord in the posterior spinal arterial supply area as a result of intervertebral disc embolism (author's transl)].

    PubMed

    Budka, H; Perneczky, A; Pusch, S

    1979-09-14

    A female patient aged 49 developed an acute transverse lesion of the spinal cord from D11 downwards. Autopsy revealed spinal cord infarcts mainly in the dorsal parts corresponding to the posterior spinal arterial supply area, caused by multiple arterial and venous fibrocartilaginous emboli. This particular cause of spinal vascular syndrome has been reported previously only in 11 patients, all outside Austria. This case report serves to stress the poor clinical delineation of a distinct "posterior spinal syndrome". The source of the emboli is the intervertebral disc, mainly the nucleus pulposus. The spinal cord vessels are probably entered by the following route: extrusion of disc material into the venous bone marrow sinus (probably favoured by trauma or endocrine factors) yield basivertebral veins yield internal vertebral venous plexus; the spread is supported by blood stream changes caused by increased intraabdominal/intrathoracic pressure; there is also the possibility of direct penetration of disc material into the internal vertebral plexus, as demonstrated in dogs yield radicular veins yield meningeal and cord veins; sometimes entry occurs through arteriovenous shunts into cord arteries. The true incidence of this condition is unknown since cases are likely to be overlooked in the absence of extensive histopathological investigation.

  5. The high-throughput phenotyping of the viscoelastic behavior of whole mouse intervertebral discs using a novel method of dynamic mechanical testing.

    PubMed

    Liu, Jennifer W; Abraham, Adam C; Tang, Simon Y

    2015-07-16

    Intervertebral disc (IVD) degeneration is highly correlated with lower back pain, and thus understanding the mechanisms of IVD degeneration is critical for the treatment of this disease. Utilizing mouse models to probe the mechanisms of degeneration is especially attractive due to the ease of manipulating mouse models and the availability of transgenics. Yet characterizing the mechanical behavior of mice IVDs remain challenging due to their minute size (approximately 540 μm in height and 1080 μm(2) in cross sectional area). We have thus developed a simple method to dynamically characterize the mechanical properties of intact mouse IVDs. The IVDs were dissected with the endplates intact, and dynamically compressed in the axial direction at 1% and 5% peak strains at 1 Hz. Utilizing this novel approach, we examined the effects of in vitro ribosylation and trypsin digestion for 24 or 72 h on the viscoelastic behavior of the whole murine IVD. Trypsin treatment resulted in a decrease of proteoglycans and loss of disc height, while ribosylation had no effect on structure or proteoglycan composition. The 72 h ribosylation group exhibited a stiffening of the disc, and both treatments significantly reduced viscous behavior of the IVDs, with the effects being more pronounced at 5% strain. Here we demonstrate a novel high-throughput method to mechanically characterize murine IVDs and detect strain-dependent differences in the elastic and the viscous behavior of the treated IVDs due to ribose and trypsin treatments.

  6. Efficacy of Anti-NaV1.7 Antibody on the Sensory Nervous System in a Rat Model of Lumbar Intervertebral Disc Injury

    PubMed Central

    Nojima, Daisuke; Inage, Kazuhide; Sakuma, Yoshihiro; Sato, Jun; Orita, Sumihisa; Yamauchi, Kazuyo; Eguchi, Yawara; Ochiai, Nobuyasu; Kuniyoshi, Kazuki; Aoki, Yasuchika; Nakamura, Junichi; Miyagi, Masayuki; Suzuki, Miyako; Kubota, Gou; Sainoh, Takeshi; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Gen; Takahashi, Kazuhisa

    2016-01-01

    Purpose The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. Materials and Methods Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti-NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated. Results The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05). Conclusion NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration. PMID:26996577

  7. Comparison of the more than 5-year clinical outcomes of cervical disc arthroplasty versus anterior cervical discectomy and fusion

    PubMed Central

    Shao, Min-Min; Chen, Chun-Hui; Lin, Zhong-Ke; Wang, Xiang-Yang; Huang, Qi-Shan; Chi, Yong-Long; Wu, Ai-Min

    2016-01-01

    Abstract Background: Anterior cervical discectomy and fusion (ACDF) was almost the “golden standard” technique in treatment of symptomatic cervical degenerative disc disease, however, it cause motion loss of the indexed level, increase the intradiscal pressure and motion of the adjacent levels, and may accelerate the degeneration of adjacent level. Cervical disc arthroplasty (CDA) was designed to preserve the motion of index level, avoid the over-activity of adjacent levels and reduce the degeneration of adjacent disc levels, the process of degeneration of adjacent level is very slowly, long term follow up studies should be conducted, this study aim to compare the more than 5 years’ long-term clinical outcomes and safety between CDA and ACDF. Methods: A systematic review and meta-analysis that will be performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The electric database of Medline, Embase, and Cochrane library will be systematic search. A standard data form will be used to extract the data of included studies. We will assess the studies according to the Cochrane Handbook for Systematic Reviews of Interventions, and perform analysis in software STATA 12.0. Fixed-effects models will be used for homogeneity data, while random-effects will be used for heterogeneity data. The overall effect sizes will be determined as weighted mean difference (WMD) for continuous outcomes and Relative risk (RR) for dichotomous outcomes. Results: The results of study will be disseminated via both international conference and peer-review journal. Conclusion: The conclusion of our study will provide the long-term and updated evidence of clinical outcomes and safety between CDA and ACDF, and help surgeon to change better surgical technique for patients. PMID:28002345

  8. Correlations between severity of clinical signs and histopathological changes in 60 dogs with spinal cord injury associated with acute thoracolumbar intervertebral disc disease.

    PubMed

    Henke, D; Vandevelde, M; Doherr, M G; Stöckli, M; Forterre, F

    2013-10-01

    The outcome of spinal surgery in dogs with absent voluntary motor function and nociception following intervertebral disc (IVD) herniation is highly variable, which likely attests to differences in the severity of spinal cord damage. This retrospective study evaluated the extent to which neurological signs correlated with histologically detected spinal cord damage in 60 dogs that were euthanased because of thoracolumbar IVD herniation. Clinical neurological grades correlated significantly with the extent of white matter damage (P<0.001). However, loss of nociception also occurred in 6/31 (19%) dogs with relatively mild histological changes. The duration of clinical signs, Schiff-Sherrington posture, loss of reflexes and pain on spinal palpation were not significantly associated with the severity of spinal cord damage. Although clinical-pathological correlation was generally good, some clinical signs frequently thought to indicate severe cord injury did not always correlate with the degree of cord damage, suggesting functional rather than structural impairment in some cases.

  9. The Effects of Stretching with Lumbar Traction on VAS and Oswestry Scales of Patients with Lumbar 4–5 Herniated Intervertebral Disc

    PubMed Central

    Yang, Hae-sun; Yoo, Won-gyu

    2014-01-01

    [Purpose] This study investigated the effect of stretching with lumbar traction on VAS and Oswestry scale scores of lumbar 4–5 herniated intervertebral disc (HIVD) patients. [Subjects] We recruited 20 lumbar 4–5 HIVD patients. [Methods] We performed stretching with lumbar traction for lumbar 4–5 HIVD patients during 4 weeks. The VAS and Oswestry scales were measured before and 4 weeks after the intervention. [Results] The results showed a significant decrease in VAS scale scores for stretching with lumbar traction in lumbar 4–5 HIVD patients, from 18±1.29 to 2.1±1.35. The Oswestry scale scores also decreased significantly, from 20.35±2.01 to 3.5±2.84, after stretching with lumbar traction. [Conclusion] Thus, we suggest stretching with lumbar traction for lumbar 4–5 HIVD patients. PMID:25140094

  10. Surgical Decompression in Dogs with Thoracolumbar Intervertebral Disc Disease and Loss of Deep Pain Perception: A Retrospective Study of 46 Cases

    PubMed Central

    Laitinen, Outi M; Puerto, David A

    2005-01-01

    The case details and outcome after surgical decompression of 46 dogs with thoracolumbar intervertebral disc disease with loss of deep pain perception prior to surgery were reviewed. Nineteen dogs (41.3%) recovered with a median follow-up period of 12.5 months. Recovery was defined as an ambulatory paraparesis, or better, with urinary and fecal continence. There was a better outcome in dogs with loss of deep pain for less than 24 hours prior to surgery (19/41; 46.3% recovered) than in dogs without deep pain perception for more than 24 hours (0/5; 0% recovered). Dogs with deep pain perception present at two weeks postoperatively had significantly higher success rate (8/12; 66.7% recovered) than dogs without deep pain perception at this time period (1/10; 10.0% recovered). The return of deep pain perception by two weeks postoperatively can be a useful positive prognostic indicator. PMID:16108215

  11. The NEtherlands Cervical Kinematics (NECK) Trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study

    PubMed Central

    2010-01-01

    Background Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Methods/Design Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Discussion Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prothesis is necessary and cost-effective will be determined by this trial. Trial Registration Netherlands

  12. Cervical Intradural Disc Herniation Causing Progressive Quadriparesis After Spinal Manipulation Therapy

    PubMed Central

    Yang, Hwan-Seo; Oh, Young-Min; Eun, Jong-Pil

    2016-01-01

    Abstract Cervical intradural disc herniation (IDH) is an extremely rare condition, comprising only 0.27% of all disc herniations. Three percent of IDHs occur in the cervical, 5% in the thoracic, and over 92% in the lumbar spinal canal. There have been a total of 31 cervical IDHs reported in the literature. The pathogenesis and imaging characteristics of IDH are not fully understood. A preoperative diagnosis is key to facilitating prompt intradural exploration in patients with ambivalent findings, as well as in preventing reoperation. The purpose of reporting our case is to remind clinicians to consider the possibility of cervical IDH during spinal manipulation therapy in patient with chronic neck pain. The patient signed informed consent for publication of this case report and any accompanying image. The ethical approval of this study was waived by the ethics committee of Chonbuk National University Hospital, because this study was case report and the number of patients was <3. A 32-year-old man was transferred our emergency department with progressive quadriparesis. He had no history of trauma, but had received physical therapy with spinal manipulation for chronic neck pain over the course of a month. The day prior, he had noticed neck pain and tingling in the bilateral upper and lower extremities during the manipulation procedure. The following day, he presented with bilateral weakness of all 4 extremities, which rendered him unable to walk. Neurological examination demonstrated a positive Hoffmann sign and ankle clonus bilaterally, hypoesthesia below the C5 dermatome, 3/5 strength in the bilateral upper extremities, and 2/5 strength in the lower extremities. This motor weakness was progressive, and he further complained of voiding difficulty. Urgent magnetic resonance imaging (MRI) of the cervical spine revealed large, central disc herniations at C4–C5 and C5–C6 that caused severe spinal cord compression and surrounding edema. We performed C4–C5–C6

  13. Investigation of different cell types and gel carriers for cell-based intervertebral disc therapy, in vitro and in vivo studies.

    PubMed

    Henriksson, H B; Hagman, M; Horn, M; Lindahl, A; Brisby, H

    2012-10-01

    Biological treatment options for the repair of intervertebral disc damage have been suggested for patients with chronic low back pain. The aim of this study was to investigate possible cell types and gel carriers for use in the regenerative treatment of degenerative intervertebral discs (IVD). In vitro: human mesenchymal cells (hMSCs), IVD cells (hDCs), and chondrocytes (hCs) were cultivated in three gel types: hyaluronan gel (Durolane®), hydrogel (Puramatrix®), and tissue-glue gel (TISSEEL®) in chondrogenic differentiation media for 9 days. Cell proliferation and proteoglycan accumulation were evaluated with microscopy and histology. In vivo: hMSCs or hCs and hyaluronan gel were co-injected into injured IVDs of six minipigs. Animals were sacrificed at 3 or 6 months. Transplanted cells were traced with anti-human antibodies. IVD appearance was visualized by MRI, immunohistochemistry, and histology. Hyaluronan gel induced the highest cell proliferation in vitro for all cell types. Xenotransplanted hMSCs and hCs survived in porcine IVDs for 6 months and produced collagen II in all six animals. Six months after transplantation of cell/gel, pronounced endplate changes indicating severe IVD degeneration were observed at MRI in 1/3 hC/gel, 1/3 hMSCs/gel and 1/3 gel only injected IVDs at MRI and 1/3 hMSC/gel, 3/3 hC/gel, 2/3 gel and 1/3 injured IVDs showed positive staining for bone mineralization. In 1 of 3 discs receiving hC/gel, in 1 of 3 receiving hMSCs/gel, and in 1 of 3 discs receiving gel alone. Injected IVDs on MRI results in 1 of 3 hMSC/gel, in 3 of 3 hC/gel, in 2 of 3 gel, and in 1 of 3 injured IVDs animals showed positive staining for bone mineralization. The investigated hyaluronan gel carrier is not suitable for use in cell therapy of injured/degenerated IVDs. The high cell proliferation observed in vitro in the hyaluronan could have been a negative factor in vivo, since most cell/gel transplanted IVDs showed degenerative changes at MRI and

  14. A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin, biglycan, fibromodulin) proteoglycans of the intervertebral disc

    PubMed Central

    MELROSE, JAMES; GHOSH, PETER; TAYLOR, THOMAS K. F.

    2001-01-01

    This study provides a comparative analysis of the temporal and spatial distribution of 5 intervertebral disc (IVD) proteoglycans (PGs) in sheep. The main PGs in the 2 and 10 y old sheep groups were polydisperse chondroitin sulphate and keratan sulphate substituted species. Their proportions did not differ markedly either with spinal level or disc zone. In contrast, the fetal discs contained 2 slow migrating (by composite agarose polyacrylamide gel electrophoresis, CAPAGE), relatively monodisperse chondroitin sulphate-rich aggrecan species which were also identified by monoclonal antibody 7-D-4 to an atypical chondroitin sulphate isomer presentation previously found in chick limb bud, and shark cartilage. The main small PG detectable in the fetal discs was biglycan, whereas decorin predominated in the 2 and 10 y old IVD samples; its levels were highest in the outer annulus fibrosus (AF). Versican was most abundant in the AF of the fetal sheep group; it was significantly less abundant in the 2 and 10 y old groups. Furthermore, versican was immunolocalised between adjacent layers of annular lamellae suggesting that it may have some role in the provision of the viscoelastic properties to this tissue. Versican was also diffusely distributed throughout the nucleus pulposus of fetal IVDs, and its levels were significantly lower in adult IVD specimens. This is the first study to identify versican in ovine IVD tissue sections and confirmed an earlier study which demonstrated that ovine IVD cells synthesised versican in culture (Melrose et al. 2000). The variable distribution of the PGs identified in this study provides further evidence of differences in phenotypic expression of IVD cell populations during growth and development and further demonstrates the complexity of the PGs in this heterogeneous but intricately organised connective tissue. PMID:11215765

  15. Depression, social factors, and pain perception before and after surgery for lumbar and cervical degenerative vertebral disc disease

    PubMed Central

    Jabłońska, Renata; Ślusarz, Robert; Królikowska, Agnieszka; Haor, Beata; Antczak, Anna; Szewczyk, Maria

    2017-01-01

    Objectives The purpose of this study was to evaluate the effects of psychosocial factors on pain levels and depression, before and after surgical treatment, in patients with degenerative lumbar and cervical vertebral disc disease. Patients and methods The study included 188 patients (98 women, 90 men) who were confirmed to have cervical or lumbar degenerative disc disease on magnetic resonance imaging, and who underwent a single microdiscectomy procedure, with no postoperative surgical complications. All patients completed two questionnaires before and after surgery – the Beck Depression Inventory scale (I–IV) and the Visual Analog Scale for pain (0–10). On hospital admission, all patients completed a social and demographic questionnaire. The first pain and depression questionnaire evaluations were performed on the day of hospital admission (n=188); the second on the day of hospital discharge, 7 days after surgery (n=188); and the third was 6 months after surgery (n=140). Results Patient ages ranged from 22 to 72 years, and 140 patients had lumbar disc disease (mean age, 42.7±10.99 years) and 44 had cervical disc disease (mean age, 48.9±7.85 years). Before surgery, symptoms of depression were present in 47.3% of the patients (11.7% cervical; 35.6% lumbar), at first postoperative evaluation in 25.1% of patients (7% cervical; 18.1% lumbar), and 6 months following surgery in 31.1% of patients (7.5% cervical; 23.6% lumbar). Patients with cervical disc disease who were unemployed had the highest incidence of depression before and after surgery (p=0.037). Patients with lumbar disc disease who had a primary level of education or work involving standing had the highest incidence of depression before and after surgery (p=0.368). Conclusion This study highlighted the association between social and demographic factors, pain perception, and depression that may persist despite surgical treatment for degenerative vertebral disc disease. PMID:28115868

  16. Interleukin-6 and interleukin-6 receptor expression, localization, and involvement in pain-sensing neuron activation in a mouse intervertebral disc injury model.

    PubMed

    Sainoh, Takeshi; Orita, Sumihisa; Miyagi, Masayuki; Sakuma, Yoshihiro; Yamauchi, Kazuyo; Suzuki, Miyako; Kubota, Go; Oikawa, Yasuhiro; Inage, Kazuhide; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Inoue, Gen; Aoki, Yasuchika; Takahashi, Kazuhisa; Ohtori, Seiji

    2015-10-01

    The pathological mechanism of intractable low back pain is unclear. However, intervertebral disc (IVD) degeneration is a primary cause of low back pain, and pain-related mediators, such as interleukin-6 (IL-6), have been correlated with discogenic pain. The objective of this study is to elucidate the mechanism of local IL-6 and IL-6 receptor (IL-6R) expression after IVD injury as well as determine the involvement of IL-6/IL-6 signaling in discogenic pain. To do this, quantitative and immunohistological analyses in a mouse model of IVD injury were performed. Firstly, we measured the local expression levels of IL-6 and IL-6R in IVDs by enzyme-linked immunosorbent assay (ELISA). Secondly, we immunohistochemically confirmed their localization in injured IVDs. Lastly, we evaluated the effects of intradiscal injection of an IL-6 inhibitor by evaluating pain-related protein, calcitonin gene-related peptide (CGRP), expression in dorsal root ganglia (DRG) neurons that innervate IVDs. Injured IVDs showed increased production of IL-6 and IL-6R. IL-6 and IL-6R expression in the injured IVD were predominantly localized in the annulus fibrosus and endplate, and intradiscal injection of the IL-6 inhibitor suppressed CGRP expression in the DRG neurons. These results show that IL-6 and IL-6R expression levels are responsive to IVD injury and that inhibition of IL-6/IL-6R signaling may be a promising analgesic treatment for degenerative disc diseases.

  17. SIRT1 alleviates senescence of degenerative human intervertebral disc cartilage endo-plate cells via the p53/p21 pathway

    PubMed Central

    Zhou, Nian; Lin, Xin; Dong, Wen; Huang, Wei; Jiang, Wei; Lin, Liangbo; Qiu, Quanhe; Zhang, Xiaojun; Shen, Jieliang; Song, Zhaojun; Liang, Xi; Hao, Jie; Wang, Dawu; Hu, Zhenming

    2016-01-01

    Cartilage end plates (CEP) degeneration plays an integral role in intervertebral disc (IVD) degeneration resulting from nutrient diffusion disorders. Although cell senescence resulting from oxidative stress is known to contribute to degeneration, no studies concerning the role of senescence in CEP degeneration have been conducted. SIRT1 is a longevity gene that plays a pivotal role in many cellular functions, including cell senescence. Therefore, the aim of this study was to investigate whether senescence is more prominent in human degenerative CEP and whether SIRT1-regulated CEP cells senescence in degenerative IVD as well as identify the signaling pathways that control that cell fate decision. In this study, the cell senescence phenotype was found to be more prominent in the CEP cells obtained from disc degenerative disease (DDD) patients than in the CEP cells obtained from age-matched lumbar vertebral fractures (LVF) patients. In addition, the results indicated that p53/p21 pathway plays an important role in the senescence of CEP cells in vivo and vitro. Furthermore, SIRT1 was found to be capable of alleviating the oxidative stress-induced senescence of CEP cells in humans via p53/p21 pathway. Thus, the information presented in this study could be used to further investigate the underlying mechanisms of CEP. PMID:26940203

  18. Ablation of intervertebral discs in dogs using a MicroJet-assisted dye-enhanced injection device coupled with the diode laser

    NASA Astrophysics Data System (ADS)

    Bartels, Kenneth E.; Henry, George A.; Dickey, D. Thomas; Stair, Ernest L.; Powell, Ronald; Schafer, Steven A.; Nordquist, Robert E.; Frederickson, Christopher J.; Hayes, Donald J.; Wallace, David B.

    1998-07-01

    Use of holmium laser energy for vaporization/coagulation of the nucleus pulposus in canine intervertebral discs has been previously reported and is currently being applied clinically in veterinary medicine. The procedure was originally developed in the canine model and intended for potential human use. Since the pulsed (15 Hz) holmium laser energy exerts photomechanical and photothermal effects, the potential for extrusion of additional disc material to the detriment of the patient is possible using the procedure developed for the dog. To reduce this potential complication, use of diode laser (805 nm - CW mode) energy, coupled with indocyanine green (ICG) as a selective laser energy absorber, was formulated as a possible alternative. Delivery of the ICG and diode laser energy was through a MicroJet device that could dispense dye interactively between individual laser 'shots.' Results have shown that it is possible to selectively ablate nucleus pulposus in the canine model using the device described. Acute observations (gross and histopathologic) illustrate that accurate placement of the spinal needle before introduction of the MicroJet device is critically dependent on the expertise of the interventional radiologist. In addition, the success of the overall technique depends on consistent delivery of both ICG and diode laser energy. Minimizing tissue carbonization on the tip of the MicroJet device is also of crucial importance for effective application of the technique in clinical veterinary medicine.

  19. Quantitative Discomanometry: Correlation of Intradiscal Pressure Values to Pain Reduction in Patients With Intervertebral Disc Herniation Treated With Percutaneous, Minimally Invasive, Image-Guided Techniques

    SciTech Connect

    Filippiadis, Dimitrios K. Mazioti, A. Papakonstantinou, O. Brountzos, E.; Gouliamos, A.; Kelekis, N. Kelekis, A.

    2012-10-15

    Purpose: To illustrate quantitative discomanometry's (QD) diagnostic efficacy and predictive value in discogenic-pain evaluation in a prospective study correlating intradiscal pressure values with pain reduction after percutaneous image-guided technique (i.e., percutaneous decompression, PD). Materials and Methods: During the last 3 years, 36 patients [21 male and 15 female (mean age 36 {+-} 5.8 years)] with intervertebral disc hernia underwent QD before PD. Under absolute sterilization and fluoroscopy, a mixture of contrast medium and normal saline (3:1 ratio) was injected. A discmonitor performed a constant rate injection and recorded pressure and volume values, thus producing the relative pressure-volume curve. PD was then performed. Pain reduction and improved mobility were recorded at 3, 12, and 24 months after PD using clinical evaluation and a numeric visual scale (NVS; 0 to 10 units). Results: Mean pain values of 7.5 {+-} 1.9 (range 4 to 8) NVS units were recorded before PD; these decreased to 2.9 {+-} 2.44 at 3 months, 1.0 {+-} 1.9 at 12 months, and 1.0 {+-} 1.9 NVS units at 24 months after PD. Recorded correlations (pressure, volume, significant pain-reduction values) with bilateral statistical significance included a maximum injected volume of 2.4 ml (p = 0.045), P{sub o} < 14 psi [initial pressure required to inject 0.1 ml of the mixture inside the disc (p = 0.05)], P{sub max} {<=} 65 psi [greatest pressure value on the curve (p = 0.018)], and P{sub max} - P{sub o} {<=} 47 psi (p = 0.038). Patients meeting these pressure or volume cut-off points, either independently or as a total, had significant pain reduction (>4 NVS units) after PD. No complications were noted. Conclusions: QD is an efficient technique that may have predictive value for discogenic pain evaluation. It might serve as a useful tool for patient selection for intervertebral disc therapies.

  20. Development of a rapid matrix digestion technique for ultrastructural analysis of elastic fibers in the intervertebral disc.

    PubMed

    Tavakoli, Javad; Costi, John J

    2017-03-21

    Collagen and elastic fibers are two major fibrous constituents of the annulus fibrosus (AF) in the disc that contribute to its mechanical and viscoelastic properties. It was thought that elastic fibers play no substantial role in the function and properties of the disc as these fibers were irregularly distributed. Studies that have revealed highly organized elastic fibers with different regional orientation and distribution, while being strongly crosslinked with matrix, suggesting their contribution to disc structure-function properties. These studies that were performed by light microscopic analysis of histologically prepared samples, have not been able to reveal the fine-scale architectural details of the elastic fiber network. Since elastic fibers are intermingled with other fibrous components of the disc and mostly obscured by the extracellular matrix, it is difficult to demonstrate their ultra-structural organization using scanning electron microscopy (SEM). Therefore the aim of this study was to develop a rapid matrix digestion technique for ultrastructural analysis of the disc elastic fibers. This study provides a new method for fundamental visualization of elastic fibers and their architecture in the disc. Through the ultra-structural analysis, the relationship between structure and function, as well as the role of elastic fibers on AF mechanical properties can be studied. This method may be used to develop a three-dimensional map of elastic fibers distribution within the disc, which would provide valuable information for designing tissue engineered scaffolds for AF repair and replacement.

  1. 1991 Volvo Award in clinical sciences. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins.

    PubMed

    Battié, M C; Videman, T; Gill, K; Moneta, G B; Nyman, R; Kaprio, J; Koskenvuo, M

    1991-09-01

    The primary objective of this study was to determine whether disc degeneration, as assessed through magnetic resonance imaging, is greater in smokers than in nonsmokers. To control for the maximum number of potentially confounding variables, pairs of identical twins highly discordant for cigarette smoking were selected as study subjects. Data analyses revealed 18% greater mean disc degeneration scores in the lumbar spines of smokers as compared with nonsmokers. The effect was present across the entire lumbar spine, implicating a mechanism acting systemically. This investigation demonstrates the efficiency of using carefully selected controls in studying conditions of multifactorial etiology, such as disc degeneration.

  2. Expression of Prolyl Hydroxylases (PHDs) Is Selectively Controlled by HIF-1 and HIF-2 Proteins in Nucleus Pulposus Cells of the Intervertebral Disc

    PubMed Central

    Fujita, Nobuyuki; Markova, Dessislava; Anderson, D. Greg; Chiba, Kazuhiro; Toyama, Yoshiaki; Shapiro, Irving M.; Risbud, Makarand V.

    2012-01-01

    Adaptive response to hypoxia in nucleus pulposus cells of the intervertebral disc is regulated by the hypoxia-inducible factors, HIF-1α and HIF-2α. Moreover, oxygen-dependent turnover of HIF-1α in these cells is controlled by the prolyl-4-hydroxylase domain (PHD) family of proteins. Whether HIF homologues control expression of PHDs and whether PHDs control hypoxia-inducible factor (HIF) turnover and/or activity under hypoxia is not known. Here, we show that in nucleus pulposus cells, hypoxia robustly induces PHD3 expression and, to a lesser extent, of PHD2 and PHD1. Reporter analysis shows that the hypoxic induction of the PHD2 promoter is HIF-1α dependent, whereas PHD3 promoter/enhancer activity is dependent on both HIF-1α and HIF-2α. Lentiviral delivery of HIF-1α, ShHIF-1α, and ShHIF-1β confirmed these observations. Noteworthy, HIF-1α maintains basal expression of PHD1 in hypoxia at the posttranscriptional level. Finally, loss of function studies using lentiviral transduction of ShPHDs clearly shows that even at 1% O2, PHD2 selectively degrades HIF-1α. In contrast, in hypoxia, PHD3 enhances HIF-1α transcriptional activity without affecting protein levels. To correlate these observations with disc disease, a condition characterized by tissue vascularization, we analyzed human tissues. Increased PHD1 mRNA expression but decreased PHD2 and PHD3 expression is observed in degenerate tissues. Interestingly, the hypoxic responsiveness of all the PHDs is maintained in isolated nucleus pulposus cells regardless of the disease state. We propose that PHD2 and PHD3 can be used as a biomarker of tissue oxygenation in the disc and that, as such, it may have important clinical implications. PMID:22451659

  3. Circadian factors BMAL1 and RORα control HIF-1α transcriptional activity in nucleus pulposus cells: implications in maintenance of intervertebral disc health

    PubMed Central

    Suyama, Kaori; Silagi, Elizabeth S.; Choi, Hyowon; Sakabe, Kou; Mochida, Joji; Shapiro, Irving M.; Risbud, Makarand V.

    2016-01-01

    BMAL1 and RORα are major regulators of the circadian molecular oscillator. Since previous work in other cell types has shown cross talk between circadian rhythm genes and hypoxic signaling, we investigated the role of BMAL1 and RORα in controlling HIF-1-dependent transcriptional responses in NP cells that exist in the physiologically hypoxic intervertebral disc. HIF-1-dependent HRE reporter activity was further promoted by co-transfection with either BMAL1 or RORα. In addition, stable silencing of BMAL1 or inhibition of RORα activity resulted in decreased HRE activation. Inhibition of RORα also modulated HIF1α-TAD activity. Interestingly, immunoprecipitation studies showed no evidence of BMAL1, CLOCK or RORα binding to HIF-1α in NP cells. Noteworthy, stable silencing of BMAL1 as well as inhibition of RORα decreased expression of select HIF-1 target genes including VEGF, PFKFB3 and Eno1. To delineate if BMAL1 plays a role in maintenance of disc health, we studied the spinal phenotype of BMAL1-null mice. The lumbar discs of null mice evidenced decreased height, and several parameters associated with vertebral trabecular bone quality were also affected in nulls. In addition, null animals showed a higher ratio of cells to matrix in NP tissue and hyperplasia of the annulus fibrosus. Taken together, our results indicate that BMAL1 and RORα form a regulatory loop in the NP and control HIF-1 activity without direct interaction. Importantly, activities of these circadian rhythm molecules may play a role in the adaptation of NP cells to their unique niche. PMID:27049729

  4. A case of cervical metastases in a patient with preexisting cervical disc replacement and fusion after 2-year symptom-free interval: when do we need interdisciplinary diagnostics?

    PubMed Central

    Melloh, Markus; Barz, Thomas

    2012-01-01

    Recurrent cervical symptoms frequently occur after cervical disc replacement and fusion. To date, no algorithm for the diagnostic assessment of these symptoms has been established. We present a case report and review of the literature to illustrate the need for interdisciplinary diagnostics in recurrent cervicobrachialgia without pathological cervical imaging. The hospital chart, medical history, physical examination, and imaging of a single patient were reviewed. A 53-year-old man with preexisting cervical disc replacement and fusion presented with a new episode of cervicobrachialgia after a 2-year symptom-free interval. Cervical magnetic resonance imaging (MRI) showed no pathological findings. Six months later the patient reported increasing symptoms including numbness and weakness of the right arm. Repeated cervical MRI and thoracic computed tomography revealed cervical metastases with intraspinal tumor growth and an underlying extensive small cell bronchial carcinoma. In recurrent cervicobrachialgia, without pathological cervical imaging, interdisciplinary diagnostics are needed. Basic diagnostic tests may assist to exclude severe non-vertebrogenic pathologies. PMID:23526906

  5. Brachioradial pruritus in a patient with cervical disc herniation and Parsonage-Turner syndrome.

    PubMed

    Carvalho, Sandrina; Sanches, Madalena; Alves, Rosário; Selores, Manuela

    2015-01-01

    Brachioradial pruritus is a chronic sensory neuropathy of unknown etiology which affects the skin of the shoulders, arms and forearms on the insertion of the brachioradialis muscle. We describe the case of a 60-year old woman recently diagnosed with multiple myeloma who refers paresis, severe pruritus and itching lesions on the right arm with 6 months of evolution. Investigation led to a diagnosis of Brachioradial pruritus consequent to the presence of cervical disc herniation and Parsonage-Turner syndrome. The patient started gabapentin 900 mg/day with good control of itching. Corticosteroids and antihistamines are often ineffective in the treatment of BP. Gabapentin has been used with encouraging results. All patients with Brachioradial pruritus should be evaluated for cervical spine injuries.

  6. Brachioradial pruritus in a patient with cervical disc herniation and Parsonage-Turner syndrome*

    PubMed Central

    Carvalho, Sandrina; Sanches, Madalena; Alves, Rosário; Selores, Manuela

    2015-01-01

    Brachioradial pruritus is a chronic sensory neuropathy of unknown etiology which affects the skin of the shoulders, arms and forearms on the insertion of the brachioradialis muscle. We describe the case of a 60-yearold woman recently diagnosed with multiple myeloma who refers paresis, severe pruritus and itching lesions on the right arm with 6 months of evolution. Investigation led to a diagnosis of Brachioradial pruritus consequent to the presence of cervical disc herniation and Parsonage-Turner syndrome. The patient started gabapentin 900mg/day with good control of itching. Corticosteroids and antihistamines are often ineffective in the treatment of BP. Gabapentin has been used with encouraging results. All patients with Brachioradial pruritus should be evaluated for cervical spine injuries. PMID:26131874

  7. Total disc replacement in the cervical spine: a systematic review evaluating long-term safety

    PubMed Central

    Anderson, Paul A.; Hashimoto, Robin

    2012-01-01

    Study design: Systematic review. Clinical questions: What are the rates and causes of subsequent surgeries? What is the long-term complication rates following cervical artificial disc replacement (C-ADR)? How do these rates change over time? Methods: A systematic review was undertaken for articles published up to October 2011. Electronic databases and reference lists of key articles were searched to identify comparative and non-comparative studies reporting long-term (≥ 48 months) complications of C-ADR. Two independent reviewers assessed the strength of evidence using the GRADE criteria and disagreements were resolved by consensus. Results: Two RCTs reporting outcomes following C-ADR (Bryan disc, Prestige disc) versus anterior cervical discectomy and fusion (ACDF) at follow-ups of 4 to 5 years were found; five case series reporting outcomes following C-ADR at follow-ups of 4 to 8 years were identified. Secondary surgery rates were similar or slightly lower following C-ADR compared with fusion at 4 to 5 years postoperatively. In one small subset of an RCT, rates of adjacent disc heterotopic ossification were lower in C-ADR patients than in those treated with fusion. Rates of other adverse events were similar between treatment groups. Conclusions: There is low evidence on the long-term safety outcomes following C-ADR. Additional comparative studies with follow-up of at least 4 years are needed to fully understand the long-term safety outcomes of C-ADR compared with fusion. PMID:23236309

  8. Subsequent surgery rates after cervical total disc replacement using a Mobi-C Cervical Disc Prosthesis versus anterior cervical discectomy and fusion: a prospective randomized clinical trial with 5-year follow-up.

    PubMed

    Jackson, Robert J; Davis, Reginald J; Hoffman, Gregory A; Bae, Hyun W; Hisey, Michael S; Kim, Kee D; Gaede, Steven E; Nunley, Pierce Dalton

    2016-05-01

    OBJECTIVE Cervical total disc replacement (TDR) has been shown in a number of prospective clinical studies to be a viable treatment alternative to anterior cervical discectomy and fusion (ACDF) for the treatment of symptomatic degenerative disc disease. In addition to preserving motion, evidence suggests that cervical TDR may result in a lower incidence of subsequent surgical intervention than treatment with fusion. The goal of this study was to evaluate subsequent surgery rates up to 5 years in patients treated with TDR or ACDF at 1 or 2 contiguous levels between C-3 and C-7. METHODS This was a prospective, multicenter, randomized, unblinded clinical trial. Patients with symptomatic degenerative disc disease were enrolled to receive 1- or 2-level treatment with either TDR as the investigational device or ACDF as the control treatment. There were 260 patients in the 1-level study (179 TDR and 81 ACDF patients) and 339 patients in the 2-level study (234 TDR and 105 ACDF patients). RESULTS At 5 years, the occurrence of subsequent surgical intervention was significantly higher among ACDF patients for 1-level (TDR, 4.5% [8/179]; ACDF, 17.3% [14/81]; p = 0.0012) and 2-level (TDR, 7.3% [17/234]; ACDF, 21.0% [22/105], p = 0.0007) treatment. The TDR group demonstrated significantly fewer index- and adjacent-level subsequent surgeries in both the 1- and 2-level cohorts. CONCLUSIONS Five-year results showed treatment with cervical TDR to result in a significantly lower rate of subsequent surgical intervention than treatment with ACDF for both 1 and 2 levels of treatment. Clinical trial registration no.: NCT00389597 ( clinicaltrials.gov ).

  9. Artificial total disc replacement versus fusion for the cervical spine: a systematic review

    PubMed Central

    Winkler, Roman; Mad, Philipp

    2010-01-01

    Cervical total disc replacement (CTDR) has been increasingly used as an alternative to fusion surgery in patients with pain or neurological symptoms in the cervical spine who do not respond to non-surgical treatment. A systematic literature review has been conducted to evaluate whether CTDR is more efficacious and safer than fusion or non-surgical treatment. Published evidence up to date is summarised qualitatively according to the GRADE methodology. After 2 years of follow-up, studies demonstrated statistically significant non-inferiority of CTDR versus fusion with respect to the composite outcome ‘overall success’. Single patient relevant endpoints such as pain, disability or quality of life improved in both groups with no superiority of CTDR. Both technologies showed similar complication rates. No evidence is available for the comparison between CTDR and non-surgical treatment. In the long run improvement of health outcomes seems to be similar in CTDR and fusion, however, the study quality is often severely limited. After both interventions, many patients still face problems. A difficulty per se is the correct diagnosis and indication for surgical interventions in the cervical spine. CTDR is no better than fusion in alleviating symptoms related to disc degeneration in the cervical spine. In the context of limited resources, a net cost comparison may be sensible. So far, CTDR is not recommended for routine use. As many trials are ongoing, re-evaluation at a later date will be required. Future research needs to address the relative effectiveness between CTDR and conservative treatment. PMID:20936484

  10. Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study

    PubMed Central

    Colombier, Pauline; Lesoeur, Julie; Youl, Samy; Madec, Stéphane; Gauthier, Olivier; Hamel, Olivier; Guicheux, Jérôme; Clouet, Johann

    2016-01-01

    Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos' scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos' scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration. PMID:27247937

  11. Hybrid surgery versus anterior cervical discectomy and fusion for multilevel cervical degenerative disc diseases: a meta-analysis.

    PubMed

    Tian, Peng; Fu, Xin; Li, Zhi-Jun; Sun, Xiao-Lei; Ma, Xin-Long

    2015-08-26

    The objective of this meta-analysis is to compare hybrid surgery (HS) and cervical discectomy and fusion (ACDF) for multilevel cervical degenerative disc diseases (DDD). Systematic searches of all published studies through March 2015 were identified from Cochrane Library, Medline, PubMed, Embase, ScienceDirect, CNKI, WANFANG DATA and CQVIP. Randomized controlled trials (RCTs) and non-RCTs involving HS and ACDF for multilevel DDD were included. All literature was searched and assessed by two independent reviewers according to the standard of Cochrane systematic review. Data of functional and radiological outcomes in two groups were pooled, which was then analyzed by RevMan 5.2 software. One RCT and four non-RCTs encompassing 160 patients met the inclusion criteria. Meta-analysis revealed significant differences in blood loss (p = 0.005), postoperative C2-C7 ROM (p = 0.002), ROM of superior adjacent segment (p < 0.00001) and ROM of inferior adjacent segment (p = 0.0007) between the HS group and the ACDF group. No significant differences were found regarding operation time (p = 0.75), postoperative VAS (p = 0.18) and complications (p = 0.73) between the groups. Hybrid surgery demonstrated excellent clinical efficacy and radiological results. Postoperative C2-C7 ROM was closer to the physiological status. No decrease in the ROM of the adjacent segment was noted in the hybrid surgery group.

  12. Cervical Radiculopathy Due to Disc Herniation with Adjacent Facet Hypertrophy: Case Report

    PubMed Central

    YAMAHATA, Hitoshi; YASUDA, Muneyoshi; AOYAMA, Tatsuro; OSUKA, Koji; ARITA, Kazunori; TAKAYASU, Masakazu

    2014-01-01

    We report a rare case of cervical radiculopathy associated with facet hypertrophy and disc herniation. The patient was a 38-year-old woman with sudden-onset left arm pain. As conservative therapy failed to alleviate her symptoms she was referred to us. On physical examination she manifested no neurological deficits except pain and dysesthesia in the left C7 territory. Computed tomography revealed hypertrophic ossified changes in the left T1 facet joint with encroachment on the spinal canal. Magnetic resonance imaging showed compression of the spinal cord at C6/7 by disc herniation at C6/7. Anterior cervical decompression and fusion by corpectomy (C7 corpectomy and C6/T1 fixation with a titanium cage) ameliorated her pain. Facet hypertrophy in a morphologically normal cervicothoracic spine is extremely rare and its etiology is unknown. We speculate the possibility that our patient harbored a congenital anomaly and that the morphologic changes were the consequence of an injury she sustained in a traffic accident. PMID:24477059

  13. Current practice of cervical disc arthroplasty: a survey among 383 AOSpine International members.

    PubMed

    Chin-See-Chong, Timothy C; Gadjradj, Pravesh S; Boelen, Robert J; Harhangi, Biswadjiet S

    2017-02-01

    OBJECTIVE The use of cervical disc arthroplasty (CDA) in spinal practice is controversial. This may be explained by the lack of studies with a large sample size and long-term outcomes. With this survey the authors aimed to evaluate the opinions of spine surgeons on the use of CDA in the current treatment of cervical disc herniation (CDH). METHODS A web-based survey was sent to all members of AOSpine International by email using SurveyMonkey on July 18, 2016. A single reminder was sent on August 18, 2016. Questions included geographic location; specialty; associated practice model; number of discectomies performed annually; the use of CDA, anterior cervical discectomy (ACD), and anterior cervical discectomy and fusion (ACDF); and the expectations for clinical outcomes of these procedures. RESULTS A total of 383 questionnaires were analyzed. Almost all practitioners (97.9%) were male, with a mean of 15.0 ± 9.7 years of clinical experience. The majority of responders were orthopedic surgeons (54.6%). 84.3% performed ACDF as the standard technique for CDH. 47.8% of the surgeons occasionally used CDA, whereas 7.3% used CDA as standard approach for CDH. The most common arthroplasty device used was the ProDisc-C. Low evidence for benefits and higher costs were the most important reasons for not offering CDA. The risk of adjacent-level disease was considered smaller for CDA as compared with ACDF. However, ACDF was expected to have the highest effectiveness on arm pain (87.5%), followed by CDA (77.9%), while ACD had the least (12.6%). CONCLUSIONS In this survey, CDA was not considered to be the routine procedure to treat CDH. Reported benefits included the reduced risk of adjacent-level disease and preservation of motion of the neck. Lack of enough evidence on its effectiveness as well as higher costs were considered to be disadvantages of CDA. More research should be conducted on the implementation impact of CDA and the cost-effectiveness from society's perspective.

  14. Effect of Cryopreservation on Canine and Human Activated Nucleus Pulposus Cells: A Feasibility Study for Cell Therapy of the Intervertebral Disc

    PubMed Central

    Tanaka, Masahiro; Hiyama, Akihiko; Arai, Fumiyuki; Nakajima, Daisuke; Nukaga, Tadashi; Nakai, Tomoko; Mochida, Joji

    2013-01-01

    Abstract It has been shown that coculture of bone marrow–derived stromal cells (BMSCs) with intervertebral disc (IVD) nucleus pulposus (NP) cells significantly activates the biological characteristics of NP cells in animal models and in humans. We therefore predicted that activated NP cells would be a useful graft source for cellular transplantation therapy in the treatment of degenerative IVDs. However, the activation protocol is based on fresh isolation and activation of NP cells, which limits the timing of clinical application. Cell transplantation therapy could be offered to more patients than is now possible if activated NP cells could be transplanted as and when required by the condition of the patient. No study has investigated the effect of cryopreservation on NP cells after enzymatic isolation. We investigated the effects of cryopreservation of canine and human NP cells in both cell and tissue form before coculture with autologous BMSCs. Cell viability, proliferation, glycosaminoglycan production, aggrecan transcriptional activity, colony generation, and gene expression profile of the cells after cryopreservation and subsequent coculture were analyzed. The influence of cryopreservation on cell chromosomal abnormalities and tumorigenesis was also studied. The results showed that there were no clear differences between the noncryopreserved and cryopreserved cells in terms of cell viability, proliferation capacity, and capacity to synthesize extracellular matrix. Furthermore, the cells showed no apparent chromosomal abnormalities or tumorigenic ability and exhibited similar patterns of gene expression. These findings suggest that by using cryopreservation, it may be possible to transplant activated NP cells upon request for patients' needs. PMID:23914334

  15. Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study

    PubMed Central

    Le Maitre, Christine L; Hoyland, Judith A; Freemont, Anthony J

    2007-01-01

    Data implicate IL-1 in the altered matrix biology that characterizes human intervertebral disc (IVD) degeneration. In the current study we investigated the enzymic mechanism by which IL-1 induces matrix degradation in degeneration of the human IVD, and whether the IL-1 inhibitor IL-1 receptor antagonist (IL-1Ra) will inhibit degradation. A combination of in situ zymography (ISZ) and immunohistochemistry was used to examine the effects of IL-1 and IL-1Ra on matrix degradation and metal-dependent protease (MDP) expression in explants of non-degenerate and degenerate human IVDs. ISZ employed three substrates (gelatin, collagen, casein) and different challenges (IL-1β, IL-1Ra and enzyme inhibitors). Immunohistochemistry was undertaken for MDPs. In addition, IL-1Ra was introduced into degenerate IVD explants using genetically engineered constructs. The novel findings from this study are: IL-1Ra delivered directly onto explants of degenerate IVDs eliminates matrix degradation as assessed by multi-substrate ISZ; there is a direct relationship between matrix degradation assessed by ISZ and MDP expression defined by immunohistochemistry; single injections of IVD cells engineered to over-express IL-1Ra significantly inhibit MDP expression for two weeks. Our findings show that IL-1 is a key cytokine driving matrix degradation in the degenerate IVD. Furthermore, IL-1Ra delivered directly or by gene therapy inhibits IVD matrix degradation. IL-1Ra could be used therapeutically to inhibit degeneration of the IVD. PMID:17760968

  16. Measurement of local strains in intervertebral disc anulus fibrosus tissue under dynamic shear: contributions of matrix fiber orientation and elastin content.

    PubMed

    Michalek, Arthur J; Buckley, Mark R; Bonassar, Lawrence J; Cohen, Itai; Iatridis, James C

    2009-10-16

    Shear strain has been implicated as an initiator of intervertebral disc anulus failure, however a clear, multi-scale picture of how shear strain affects the tissue microstructure has been lacking. The purposes of this study were to measure microscale deformations in anulus tissue under dynamic shear in two orientations, and to determine the role of elastin in regulating these deformations. Bovine AF tissue was simultaneously shear loaded and imaged using confocal microscopy following either a buffer or elastase treatment. Digital image analysis was used to track through time local shear strains in specimens sheared transversely, and stretch and rotation of collagen fiber bundles in specimens sheared circumferentially. The results of this study suggest that sliding does not occur between AF plies under shear, and that interlamellar connections are governed by collagen and fibrilin rather than elastin. The transverse shear modulus was found to be approximately 1.6 times as high in plies the direction of the collagen fibers as in plies across them. Under physiological levels of in-plane shear, fiber bundles stretched and re-oriented linearly. Elastin was found to primarily stiffen plies transversely. We conclude that alterations in the elastic fiber network, as found with IVD herniation and degeneration, can therefore be expected to significantly influence the AF response to shear making it more susceptible to micro failure under bending or torsion loading.

  17. Development and Validation of a Bioreactor System for Dynamic Loading and Mechanical Characterization of Whole Human Intervertebral Discs in Organ Culture

    PubMed Central

    Walter, BA; Illien-Junger, S; Nasser, P; Hecht, AC; Iatridis, JC

    2014-01-01

    Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 hours of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques. PMID:24725441

  18. Development and validation of a bioreactor system for dynamic loading and mechanical characterization of whole human intervertebral discs in organ culture.

    PubMed

    Walter, B A; Illien-Jünger, S; Nasser, P R; Hecht, A C; Iatridis, J C

    2014-06-27

    Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers w