MRI cross sectional atlas of normal canine cervical musculoskeletal structure

Although magnetic resonance imaging (MRI) has been increasingly used as a diagnostic tool for cervical spine injuries in canines, a comprehensive normal MRI anatomy of the canine cervical spine muscles is lacking. Therefore, the purpose of this study was to build a magnetic resonance imaging atlas of the normal cross sectional anatomy of the muscles of the canine cervical spine. MRI scans were performed on a canine cadaver using a combination of T1 and T2-weighted images in the transverse, sagittal and dorsal planes acquired at a slice thickness of 1 mm. Muscle contours were traced manually in each slice, using local osseous structures as reference points for muscle identification. Twenty-two muscles were traced in 401 slices in the cervical region. A three dimensional surface model of all the contoured muscles was created to illustrate the complex geometrical arrangement of canine neck muscles. The cross-sectional area of the muscles was measured at the mid-level of each vertebra. The accuracy of the location of the mapped muscles was verified by comparing the sagittal view of the 3D model of muscles with still photographs obtained from anatomic canine cadaver dissection. We believe that this information will provide a unique and valuable resource for veterinary researchers, clinicians and surgeons who wish to evaluate MRI images of the cervical spine. It will also serve as the foundation for ongoing work to develop a computational model of the canine cervical spine in which anatomical information is combined with electromyographic, kinematic and kinetic data.This work was supported in part by Fitzpatrick Referrals Ltd., through the One Health/One Medicine Fellowship at The Ohio State University

Kinematic Behaviour of a Novel Pedicle Screw-Rod Fixation System for the Canine Lumbosacral Joint

Objective: To determine the biomechanical behaviour of a novel distraction-stabilization system, consisting of an intervertebral distraction bolt, polyaxial screws and connecting rods, in the canine lumbosacral spine. Study design: Biomechanical study. Sample population: Cadaveric canine lumbosacral spines (L4-Cd3) (N=8) Methods: Cadaveric lumbosacral spines were harvested, stripped of musculature, mounted on a 4-point bending jig, and tested in extension, flexion and lateral bending using non-destructive compressive axial loads (0-150N). Angular displacement was recorded from reflective optical trackers rigidly secured to L6, L7 and S1. Data for primary and coupled motion were collected from intact spines; after destabilization at L7-S1, and following surgical stabilisation with the new implant system. Results: As compared with the intact spine, laminectomy resulted in a modest increase in angular displacement at L6-L7 and a marked increase at L7-S1. Instrumentation significantly reduced motion at the operated level (L7-S1) with a concomitant increase at the adjacent level (L6-L7). Conclusion: The combination of a polyaxial pedicle screw-rod system and intervertebral spacer provides a versatile solution of surgical stabilisation of the lumbosacral joint following surgical decompression in the canine lumbosacral spine. The increase in motion at L6-L7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this question. Clinical relevance: These results support the feasibility of using this new implant system for the management of degenerative lumbosacral disease in dogs. The increase in motion at L6-L7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this question

An EMG-driven biomechanical model of the canine cervical spine

Due to the frequency of cervical spine injuries in canines, the purpose of this effort was to develop an EMG-driven dynamic model of the canine cervical spine to assess a biomechanical understanding that enables one to investigate the risk of neck disorders. A canine subject was recruited in this investigation in order to collect subject specific data. Reflective markers and a motion capture system were used for kinematic measurement; surface electrodes were used to record electromyography signals, and with the aid of force plate kinetics were recorded. A 3D model of the canine subject was reconstructed from an MRI dataset. Muscles lines of action were defined through a new technique with the aid of 3D white light scanner. The model performed well with a 0.73 weighted R$^{2}$ value in all three planes. The weighted average absolute error of the predicted moment was less than 10% of the external moment. The proposed model is a canine specific forward-dynamics model that precisely tracks the canine subject head and neck motion, calculates the muscle force generated from the twelve major moment producing muscles, and estimates resulting loads on specific spinal tissues.This work was supported in part by Fitzpatrick Referrals Ltd., through the One Health/One Medicine Fellowship at The Ohio State University

Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages

Distinguishing dendritic cells (DCs) from other cells of the mononuclear phagocyte system is complicated by the shared expression of cell surface markers such as CD11c. In this study, we identified Zbtb46 (BTBD4) as a transcription factor selectively expressed by classical DCs (cDCs) and their committed progenitors but not by plasmacytoid DCs (pDCs), monocytes, macrophages, or other lymphoid or myeloid lineages. Using homologous recombination, we replaced the first coding exon of Zbtb46 with GFP to inactivate the locus while allowing detection of Zbtb46 expression. GFP expression in Zbtb46(gfp/+) mice recapitulated the cDC-specific expression of the native locus, being restricted to cDC precursors (pre-cDCs) and lymphoid organ- and tissue-resident cDCs. GFP(+) pre-cDCs had restricted developmental potential, generating cDCs but not pDCs, monocytes, or macrophages. Outside the immune system, Zbtb46 was expressed in committed erythroid progenitors and endothelial cell populations. Zbtb46 overexpression in bone marrow progenitor cells inhibited granulocyte potential and promoted cDC development, and although cDCs developed in Zbtb46(gfp/gfp) (Zbtb46 deficient) mice, they maintained expression of granulocyte colony-stimulating factor and leukemia inhibitory factor receptors, which are normally down-regulated in cDCs. Thus, Zbtb46 may help enforce cDC identity by restricting responsiveness to non-DC growth factors and may serve as a useful marker to identify rare cDC progenitors and distinguish between cDCs and other mononuclear phagocyte lineages

Critical Role of Macrophages and Their Activation via MyD88-NFκB Signaling in Lung Innate Immunity to Mycoplasma pneumoniae

Mycoplasma pneumoniae (Mp), a common cause of pneumonia, is associated with asthma; however, the mechanisms underlying this association remain unclear. We investigated the cellular immune response to Mp in mice. Intranasal inoculation with Mp elicited infiltration of the lungs with neutrophils, monocytes and macrophages. Systemic depletion of macrophages, but not neutrophils, resulted in impaired clearance of Mp from the lungs. Accumulation and activation of macrophages were decreased in the lungs of MyD88−/− mice and clearance of Mp was impaired, indicating that MyD88 is a key signaling protein in the anti-Mp response. MyD88-dependent signaling was also required for the Mp-induced activation of NFκB, which was essential for macrophages to eliminate the microbe in vitro. Thus, MyD88-NFκB signaling in macrophages is essential for clearance of Mp from the lungs

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

International audienceABSTRACT: The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40+ antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology

Effects of image plane, patient positioning, and foraminal zone on magnetic resonance imaging measurements of canine lumbosacral intervertebral foramina

Degenerative lumbosacral stenosis has been suspected to have a dynamic component, especially regarding encroachment of the L7 nerve roots exiting the lumbosacral foramina. Angled cross-sectional imaging of the neuroforamina has been found improve the accuracy of the diagnosis of stenosis in humans. In this anatomic study, foraminal apertures were evaluated by MRI at the entry, middle, and exit zones of the nerve roots in 30 dogs that were clinically affected by lumbosacral disease. Standard vs. oblique planar orientation and neutral vs. hyperextended positioning of the lumbosacral area were compared by measuring the median values for entry, middle, and exit zones. The neuroforaminal area acquired using oblique plane acquisition was significantly smaller than standard parasagittal measurements. Furthermore, standard parasagittal neuroforaminal dimensions in the hyperextended position were significantly smaller than standard parasagittal measurements in the neutral position. This statistical difference was even more pronounced for neuroforaminal dimension evaluated in the oblique plane and hyperextended position. Positioning of the dog during imaging has a significant effect on neuroforaminal dimension, corroborating the notion that spinal position may influence neural claudication in clinically affected patients. Reductions in neuroforaminal dimension are more evident on oblique planar image acquisition, suggesting that this approach may be more useful than parasagittal imaging as a tool for identifying subtle changes in L7 neuroforaminal dimensions in cases of canine lumbosacral stenosis