Planet formation models: the interplay with the planetesimal disc

Context. According to the sequential accretion model (or core-nucleated accretion model), giant planet formation is based first on the formation of a solid core which, when massive enough, can gravitationally bind gas from the nebula to form the envelope. The most critical part of the model is the formation time of the core: to trigger the accretion of gas, the core has to grow up to several Earth masses before the gas component of the protoplanetary disc dissipates. Aims: We calculate planetary formation models including a detailed description of the dynamics of the planetesimal disc, taking into account both gas drag and excitation of forming planets. Methods: We computed the formation of planets, considering the oligarchic regime for the growth of the solid core. Embryos growing in the disc stir their neighbour planetesimals, exciting their relative velocities, which makes accretion more difficult. Here we introduce a more realistic treatment for the evolution of planetesimals' relative velocities, which directly impact on the formation timescale. For this, we computed the excitation state of planetesimals, as a result of stirring by forming planets, and gas-solid interactions. Results: We find that the formation of giant planets is favoured by the accretion of small planetesimals, as their random velocities are more easily damped by the gas drag of the nebula. Moreover, the capture radius of a protoplanet with a (tiny) envelope is also larger for small planetesimals. However, planets migrate as a result of disc-planet angular momentum exchange, with important consequences for their survival: due to the slow growth of a protoplanet in the oligarchic regime, rapid inward type I migration has important implications on intermediate-mass planets that have not yet started their runaway accretion phase of gas. Most of these planets are lost in the central star. Surviving planets have masses either below 10 M⊕ or above several Jupiter masses. Conclusions: To form giant planets before the dissipation of the disc, small planetesimals (~0.1 km) have to be the major contributors of the solid accretion process. However, the combination of oligarchic growth and fast inward migration leads to the absence of intermediate-mass planets. Other processes must therefore be at work to explain the population of extrasolar planets that are presently known.

Cardiomyocyte growth and sarcomerogenesis at the intercalated disc

Cardiomyocytes grow during heart maturation or disease-related cardiac remodeling. We present evidence that the intercalated disc (ID) is integral to both longitudinal and lateral growth: increases in width are accommodated by lateral extension of the plicate tread regions and increases in length by sarcomere insertion within the ID. At the margin between myofibril and the folded membrane of the ID lies a transitional junction through which the thin filaments from the last sarcomere run to the ID membrane and it has been suggested that this junction acts as a proto Z-disc for sarcomere addition. In support of this hypothesis, we have investigated the ultrastructure of the ID in mouse hearts from control and dilated cardiomyopathy (DCM) models, the MLP-null and a cardiac-specific β-catenin mutant, cΔex3, as well as in human left ventricle from normal and DCM samples. We find that the ID amplitude can vary tenfold from 0.2 μm up to a maximum of ~2 μm allowing gradual expansion during heart growth. At the greatest amplitude, equivalent to a sarcomere length, A-bands and thick filaments are found within the ID membrane loops together with a Z-disc, which develops at the transitional junction position. Here, also, the tops of the membrane folds, which are rich in αII spectrin, become enlarged and associated with junctional sarcoplasmic reticulum. Systematically larger ID amplitudes are found in DCM samples. Other morphological differences between mouse DCM and normal hearts suggest that sarcomere inclusion is compromised in the diseased hearts.

Finite element analyses of human vertebral bodies embedded in polymethylmethalcrylate or loaded via the hyperelastic intervertebral disc models provide equivalent predictions of experimental strength

Quantitative computer tomography (QCT)-based finite element (FE) models of vertebral body provide better prediction of vertebral strength than dual energy X-ray absorptiometry. However, most models were validated against compression of vertebral bodies with endplates embedded in polymethylmethalcrylate (PMMA). Yet, loading being as important as bone density, the absence of intervertebral disc (IVD) affects the strength. Accordingly, the aim was to assess the strength predictions of the classic FE models (vertebral body embedded) against the in vitro and in silico strengths of vertebral bodies loaded via IVDs. High resolution peripheral QCT (HR-pQCT) were performed on 13 segments (T11/T12/L1). T11 and L1 were augmented with PMMA and the samples were tested under a 4° wedge compression until failure of T12. Specimen-specific model was generated for each T12 from the HR-pQCT data. Two FE sets were created: FE-PMMA refers to the classical vertebral body embedded model under axial compression; FE-IVD to their loading via hyperelastic IVD model under the wedge compression as conducted experimentally. Results showed that FE-PMMA models overestimated the experimental strength and their strength prediction was satisfactory considering the different experimental set-up. On the other hand, the FE-IVD models did not prove significantly better (Exp/FE-PMMA: R²=0.68; Exp/FE-IVD: R²=0.71, p=0.84). In conclusion, FE-PMMA correlates well with in vitro strength of human vertebral bodies loaded via real IVDs and FE-IVD with hyperelastic IVDs do not significantly improve this correlation. Therefore, it seems not worth adding the IVDs to vertebral body models until fully validated patient-specific IVD models become available.

Finite Element Based Nonlinear Normalization of Human Lumbar Intervertebral Disc Stiffness to Account for Its Morphology

Disc degeneration, usually associated with low back pain and changes of intervertebral stiffness, represents a major health issue. As the intervertebral disc (IVD) morphology influences its stiffness, the link between mechanical properties and degenerative grade is partially lost without an efficient normalization of the stiffness with respect to the morphology. Moreover, although the behavior of soft tissues is highly nonlinear, only linear normalization protocols have been defined so far for the disc stiffness. Thus, the aim of this work is to propose a nonlinear normalization based on finite elements (FE) simulations and evaluate its impact on the stiffness of human anatomical specimens of lumbar IVD. First, a parameter study involving simulations of biomechanical tests (compression, flexion/extension, bilateral torsion and bending) on 20 FE models of IVDs with various dimensions was carried out to evaluate the effect of the disc's geometry on its compliance and establish stiffness/morphology relations necessary to the nonlinear normalization. The computed stiffness was then normalized by height (H), cross-sectional area (CSA), polar moment of inertia (J) or moments of inertia (Ixx, Iyy) to quantify the effect of both linear and nonlinear normalizations. In the second part of the study, T1-weighted MRI images were acquired to determine H, CSA, J, Ixx and Iyy of 14 human lumbar IVDs. Based on the measured morphology and pre-established relation with stiffness, linear and nonlinear normalization routines were then applied to the compliance of the specimens for each quasi-static biomechanical test. The variability of the stiffness prior to and after normalization was assessed via coefficient of variation (CV). The FE study confirmed that larger and thinner IVDs were stiffer while the normalization strongly attenuated the effect of the disc geometry on its stiffness. Yet, notwithstanding the results of the FE study, the experimental stiffness showed consistently higher CV after normalization. Assuming that geometry and material properties affect the mechanical response, they can also compensate for one another. Therefore, the larger CV after normalization can be interpreted as a strong variability of the material properties, previously hidden by the geometry's own influence. In conclusion, a new normalization protocol for the intervertebral disc stiffness in compression, flexion, extension, bilateral torsion and bending was proposed, with the possible use of MRI and FE to acquire the discs' anatomy and determine the nonlinear relations between stiffness and morphology. Such protocol may be useful to relate the disc's mechanical properties to its degree of degeneration.

Immunohistochemical demonstration of lumbar intervertebral disc innervation in the dog.

Low back pain is a common ailment in dogs, particularly in specific breeds such as the German shepherd dog. A number of structures such as facet joint capsules, ligaments, dorsal root ganglia, periosteum, vertebral endplates and meninges have been associated with this condition. Yet, in spite of all diagnostic efforts, the origin of pain remains obscure in a substantial proportion of all cases. A further structure often being involved in vertebral column disorders is the intervertebral disc. The presence of nerves, however, is a precondition for pain sensation and, consequently, structures lacking innervation can be left out of consideration as a cause for low back pain. Nerve fibres have been demonstrated at the periphery of the intervertebral disc in man, rabbit and rat. With regard to the dog, however, the extent of intervertebral disc innervation is still being disputed. The goal of the present study, therefore, was to substantiate and expand current knowledge of intervertebral disc innervation. Protein gene product (PGP) 9.5 was used for immunohistochemical examination of serial transversal and sagittal paraffin sections of lumbar discs from adult dogs. This general marker revealed nerve fibres to be confined to the periphery of the intervertebral discs. These results indicate that even limited pathological processes affecting the outer layers of the intervertebral disc are prone to cause low back pain.

Hans Brun: a Swiss pioneer in the surgery of the spinal cord, brain and herniated lumbar disc

INTRODUCTION Toward the end of the nineteenth century, it was Gowers, Horsley and Macewen who first reported successful surgical procedures for the treatment of subdural extramedullary tumors. Following this, Church and Eisendrath as well as Putnam and Warren reported unsuccessful attempts to treat subpial spinal pathologies in their patients. Only at the beginning of the twentieth century did reports of successful interventions of this type accumulate. In the analysis of these case reports, the authors noticed a certain lack of accuracy about the anatomical allocations and descriptions of intra- and extramedullary spinal lesions. From this, the question of who actually carried out the pioneering works in the early twentieth century in the field of surgery of intramedullary pathologies arose. METHODS Analysis of the relevant original publications of Hans Brun and research on the poorly documented information about his life history by personally contacting contemporary relatives. RESULTS The literature analysis showed that the Swiss neurologist Otto Veraguth and surgeon Hans Brun made fundamental contributions to subpial spinal cord surgery at the very beginning of the last century that remain valid today. According to our research, Hans Brun should be remembered as the third surgeon (after von Eiselsberg and Elsberg) who successfully removed an intramedullary lesion in a patient. CONCLUSION Brun should be remembered as an early and successful surgeon in this specialized field. His operative work is described in detail in this article. At the same time, his achievements in the fields of brain and disc herniation surgery are presented.

Influence of intervertebral disc fenestration at the herniation site in association with hemilaminectomy on recurrence in chondrodystrophic dogs with thoracolumbar disc disease: a prospective MRI study

OBJECTIVE To describe the influence of fenestration at the disc herniation site on recurrence in thoracolumbar disc disease of chondrodystrophoid dogs. STUDY DESIGN Prospective clinical study. ANIMALS Chondrodystrophic dogs (n=19). METHODS Dogs were divided into 2 groups: group 1 (9 dogs) had thoracolumbar disc extrusion (Hansen type I) treated by hemilaminectomy and concomitant fenestration of the affected intervertebral disc and group 2 (10 dogs) had hemilaminectomy without fenestration. All dogs had 3 magnetic resonance imaging (MRI) examinations: preoperatively, immediately postoperatively to assess removal of herniated disc material, and again 6 weeks after surgery. RESULTS There were 13 male and 6 female dogs; mean age, 7.1 years. Thoracolumbar disc herniation was confirmed with MRI. Immediate post surgical MRI revealed that the herniated disc removal was complete in all but 1 dog and that fenestration did not lead to complete removal of nucleus pulposus within the intervertebral disc space. On the 3rd MRI examination, none of the group 1 dogs had further disc material herniation at the fenestrated site. Six of the 10 group 2 dogs had a recurrence of herniation leading to clinical signs in 3 dogs (pain in 2 dogs, paresis in 1 dog). CONCLUSION In thoracolumbar disc herniation, fenestration of the affected intervertebral disc space prevents further extrusion of disc material. CLINICAL RELEVANCE Fenestration reduces the risk of early recurrence of disc herniation and associated postoperative complications.

Dominance of chemokine ligand 2 and matrix metalloproteinase-2 and -9 and suppression of pro-inflammatory cytokines in the epidural compartment after intervertebral disc extrusion in a canine model

BACKGROUND CONTEXT In canine intervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space. PURPOSE To determine messenger RNA (mRNA) expressions of selected cytokines, chemokines, and matrix metalloproteinases (MMPs) qualitatively and semiquantitatively over the course of the disease and to correlate results to neurologic status and outcome. STUDY DESIGN/SETTING Prospective study using extruded IVD material of dogs with thoracolumbar IVD extrusion. PATIENT SAMPLE Seventy affected and 13 control (24 samples) dogs. OUTCOME MEASURES Duration of neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome were recorded. After diagnostic imaging, decompressive surgery was performed. METHODS Messenger RNA expressions of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF), interferon (IFN)γ, MMP-2, MMP-9, chemokine ligand (CCL)2, CCL3, and three housekeeping genes was determined in the collected epidural material by Panomics 2.0 QuantiGene Plex technology. Relative mRNA expression and fold changes were calculated. Relative mRNA expression was correlated statistically to clinical parameters. RESULTS Fold changes of TNF, IL-1β, IL-2, IL-4, IL-6, IL-10, IFNγ, and CCL3 were clearly downregulated in all stages of the disease. MMP-9 was downregulated in the acute stage and upregulated in the subacute and chronic phase. Interleukin-8 was upregulated in acute cases. MMP-2 showed mild and CCL2 strong upregulation over the whole course of the disease. In dogs with severe pain, CCL3 and IFNγ were significantly higher compared with dogs without pain (p=.017/.020). Dogs pretreated with nonsteroidal anti-inflammatory drugs revealed significantly lower mRNA expression of IL-8 (p=.017). CONCLUSIONS The high CCL2 levels and upregulated MMPs combined with downregulated T-cell cytokines and suppressed pro-inflammatory genes in extruded canine disc material indicate that the epidural reaction is dominated by infiltrating monocytes differentiating into macrophages with tissue remodeling functions. These results will help to understand the pathogenic processes representing the basis for novel therapeutic approaches. The canine IVD disease model will be rewarding in this process.

Neurologic outcome after thoracolumbar partial lateral corpectomy for intervertebral disc disease in 72 dogs

OBJECTIVE To determine neurologic outcome and factors influencing outcome after thoracolumbar partial lateral corpectomy (PLC) in dogs with intervertebral disc disease (IVDD) causing ventral spinal cord compression. STUDY DESIGN Retrospective case series. ANIMALS Dogs with IVDD (n = 72; 87 PLC). METHODS Dogs with IVDD between T9 and L5 were included if treated by at least 1 PLC. Exclusion criteria were: previous spinal surgery, combination of PLC with another surgical procedure. Neurologic outcome was assessed by: (1) modified Frankel score (MFS) based on neurologic examinations at 4 time points (before surgery, immediately after PLC, at discharge and 4 weeks after PLC); and (2) owner questionnaire. The association of the following factors with neurologic outcome was analyzed: age, body weight, duration of current neurologic dysfunction (acute, chronic), IVDD localization, breed (chondrodystrophic, nonchondrodystrophic), number of PLCs, degree of presurgical spinal cord compression and postsurgical decompression, slot depth, presurgical MFS. Presurgical spinal cord compression was determined by CT myelography (71 dogs) or MRI (1 dog), whereas postsurgical decompression and slot depth were determined on CT myelography (69 dogs). RESULTS MFS was improved in 18.7%, 31.7%, and 64.2% of dogs at the 3 postsurgical assessments, whereas it was unchanged in 62.6%, 52.8%, and 32.0% at corresponding time points. Based on owner questionnaire, 91.4% of dogs were ambulatory 6 months postsurgically with 74.5% having a normal gait. Most improvement in neurologic function developed within 6 months after surgery. Presurgical MFS was the only variable significantly associated with several neurologic outcome measurements (P < .01). CONCLUSIONS PLC is an option for decompression in ventrally compressing thoracolumbar IVDD. Prognosis is associated with presurgical neurologic condition.

Minimally invasive photopolymerization in intervertebral disc tissue cavities

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 polymerization- volume 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.