Papers by Niklas Bergknut
American Journal of Veterinary Research, 2011
The Veterinary Journal, 2013
Intervertebral disc (IVD) degeneration is common in dogs and can give rise to a number of disease... more Intervertebral disc (IVD) degeneration is common in dogs and can give rise to a number of diseases, such as IVD herniation, cervical spondylomyelopathy, and degenerative lumbosacral stenosis. Although there have been many reports and reviews on the clinical aspects of canine IVD disease, few reports have discussed and reviewed the process of IVD degeneration. In this first part of a two-part review, the anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are described. In Part 2, the aspects of IVD degeneration in chondrodystrophic and nonchondrodystrophic dog breeds are discussed in depth.
The Veterinary Journal, 2013
Dogs can be grouped into two distinct types of breed based on the predisposition to chondrodystro... more Dogs can be grouped into two distinct types of breed based on the predisposition to chondrodystrophy, namely, non-chondrodystrophic (NCD) and chondrodystrophic (CD). In addition to a different process of endochondral ossification, NCD and CD breeds have different characteristics of intravertebral disc (IVD) degeneration and IVD degenerative diseases. The anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are discussed in the first part of this two-part review. This second part describes the similarities and differences in the histopathological and biochemical characteristics of IVD degeneration in CD and NCD canine breeds and discusses relevant aetiological factors of IVD degeneration.
Introduction: Early degeneration of the intervertebral disc (IVD) involves a change in cellular d... more Introduction: Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue from non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occurring IVD degeneration. Methods: Dual channel DNA microarrays were used to compare 1) healthy NP tissue containing only NCs (NC-rich), 2) NP tissue with a mixed population of NCs and CLCs (Mixed), and 3) NP tissue containing solely CLCs (CLC-rich) in both non-chondrodystrophic and chondrodystrophic dogs. Based on previous reports and the findings of the microarray analyses, canonical Wnt signaling was further evaluated using qPCR of relevant Wnt target genes. We hypothesized that caveolin-1, a regulator of Wnt signaling that showed significant changes in gene expression in the microarray analyses, played a significant role in early IVD degeneration. Caveolin-1 expression was investigated in IVD tissue sections and in cultured NCs. To investigate the significance of Caveolin-1 in IVD health and degeneration, the NP of 3-month-old Caveolin-1 knockout mice was histopathologically evaluated and compared with the NP of wild-type mice of the same age.
Partial disc replacement is a new surgical technique aimed at restoring functionality to degenera... more Partial disc replacement is a new surgical technique aimed at restoring functionality to degenerated intervertebral discs (IVDs). The aim of the present study was to assess biomechanically the behaviour of a novel nucleus pulposus prosthesis (NPP) in situ and its ability to restore functionality to the canine IVD after nuclectomy alone or after combined dorsal laminectomy and nuclectomy. Nine canine T13–L5 specimens (L2L3 group) and 10 L5–Cd1 specimens (LS group) were tested biomechanically in the native state, after nuclectomy (L2L3 group) or after combined dorsal laminectomy and nuclectomy (LS group), and after insertion of the NPP. Range of motion (ROM), neutral zone (NZ), and neutral zone stiffness (NZS) were determined in flexion/extension, lateral bending, and axial rotation. Nuclectomy alone and combined dorsal laminectomy and nuclectomy caused significant instability in all motion directions. Implantation of the NPP resulted in significant restoration of the parameters (ROM, NZ, and NZS) towards the native state; however, fragmentation/herniation of the NPP occurred in 47% of the cases. In conclusion, the NPP has the ability to improve functionality of the nuclectomized canine IVD. The high rate of NPP failure requires modifications directed at the integrity of the NPP and its confinement to the nuclear cavity.
Purpose Dogs are often used as an animal model in spinal research, but consideration should be gi... more Purpose Dogs are often used as an animal model in spinal research, but consideration should be given to the breed used as chondrodystrophic (CD) dog breeds always develop IVD degeneration at an early age, whereas non-chondrodystrophic (NCD) dog breeds may develop IVD degeneration, but only later in life. The aim of this study was to provide a mechanical characterization of the NCD [non-degenerated intervertebral discs (IVDs), rich in notochordal cells] and CD (degenerated IVDs, rich in chondrocyte-like cells) canine spine before and after de-compressive surgery (nucleotomy). Methods The biomechanical properties of multisegment-ed lumbar spine specimens (T13–L5 and L5–Cd1) from 2-year-old NCD dogs (healthy) and CD dogs (early degeneration) were investigated in flexion/extension (FE), lateral bending (LB), and axial rotation (AR), in the native state and after nucleotomy of L2–L3 or dorsal laminectomy and nucleotomy of L7–S1. The range of motion (ROM), neutral zone (NZ), and NZ stiffness (NZS) of L1–L2, L2– L3, L6–L7, and L7–S1 were calculated. Results In native spines in both dog groups, the greatest mobility in FE was found at L7–S1, and the greatest mobility in LB at L2–L3. Surgery significantly increased the ROM and NZ, and significantly decreased the NZS in FE, LB, and AR in both breed groups. However, surgery at L2–L3 resulted in a significantly larger increase in NZ and decrease in NZS in the CD spines compared with the NCD spines, whereas surgery at L7–S1 induced a significantly larger increase in ROM and decrease in NZS in the NCD spines compared with the CD spines. Conclusions Spinal biomechanics significantly differ between NCD and CD dogs and researchers should consider this aspect when using the dog as a model for spinal research.
Study Design. Prospective observational and analytic study. Objective. To investigate whether spo... more Study Design. Prospective observational and analytic study. Objective. To investigate whether spontaneous intervertebral disc degeneration (IVDD) occurring in both chondrodystrophic (CD) and nonchondrodystrophic dogs (NCD) can be used as a valid translational model for human IVDD research. Summary of Background Data. Different animal models are used in IVDD research, but in most of these models IVDD is induced manually or chemically rather than occurring spontaneously. Methods. A total of 184 intervertebral discs (IVDs) from 19 dogs of different breeds were used. The extent of IVDD was evaluated by macroscopic grading, histopathology, glycosaminoglycan content, and matrix metalloproteinase 2 activity. Canine data were compared with human IVD data acquired in this study or from the literature. Results. Gross pathology of IVDD in both dog types (CD and NCD) and humans showed many similarities, but the cartilaginous endplates were signifi cantly thicker and the subchondral cortices signifi cantly thinner in humans than in dogs. Notochordal cells were still present in the IVDs of adult NCD but were not seen in the CD breeds or in humans. Signs of degeneration were seen in young dogs of CD breeds (< 1 year of age), whereas this was only seen in older dogs of NCD breeds (5–7 years of age). The relative glycosaminoglycan content and metalloproteinase 2 activity in canine IVDD were similar to those in humans: metalloproteinase 2
Intervertebral disc (IVD) degeneration is common in dogs and can lead to serious disorders. Curre... more Intervertebral disc (IVD) degeneration is common in dogs and can lead to serious disorders. Current treatments can relieve clinical signs of disease, but do not restore IVD function. The development of regener-ative strategies for IVD dysfunction requires detailed knowledge of the pathogenesis of IVD degeneration and its underlying mechanisms. Histological examination of IVDs at different stages of degeneration might provide this knowledge, but as there is currently no histological grading scheme for canine IVD degeneration, the aim of this study, which is the first of a two-part series, was to design and validate an appropriate scheme. Three independent observers evaluated 35 IVDs at different stages of degeneration using the scheme. Glycosaminoglycan contents of the nucleus pulposus and macroscopic grading according to Thompson, which are considered 'gold standards' for IVD degeneration, were used to validate the scheme. Reproduc-ibility was assessed by analysing the inter-observer reliability of all individual variables of the grading scheme, using a weighted j analysis. Significant correlations were found between Thompson grading and total histological score (r = 0.94; P < 0.01) and between glycosaminoglycan content and total histo-logical score (r = À0.72; P < 0.01). Most individual histological variables showed 'moderate' to 'almost perfect' inter-observer reliability. The high correlation with the gold standards in combination with the high reproducibility indicates that the proposed histological grading scheme is reliable and objective for classification of IVD degeneration in both chondrodystrophic and non-chondrodystrophic dog breeds.
Objective: To assess pedicle screw-rod fixation (PSRF) of the canine lumbosacral junction (LSJ) e... more Objective: To assess pedicle screw-rod fixation (PSRF) of the canine lumbosacral junction (LSJ) ex vivo and in vivo. Study Design: Ex vivo cadaver study and in vivo pilot study. Sample Population: Six canine cadaveric lumbosacral spinal specimens and 3 Greyhound dogs diagnosed with degenerative lumbosacral stenosis (DLSS). Methods: Ex vivo study: PSRF of the LSJ was performed in 6 spinal specimens using guidelines and was evaluated by radiography, computed tomography, and magnetic resonance imaging. In vivo study: 3 Greyhounds diagnosed with DLSS had dorsal laminectomy and partial discectomy combined with PSRF of the LSJ. Curettage of the endplates with insertion of an autologous cancellous bone graft was performed to promote spinal fusion. During 18-month follow-up, dogs were monitored by clinical evaluation, diagnostic imaging, and force plate analysis. Dogs were euthanatized for reasons unrelated to PSRF or their lumbosacral disease , and postmortem imaging and histopathologic investigations of the LSJ were performed. Results: Ex vivo study: Sixteen of 24 inserted screws had an acceptable placement. In vivo study: Ten of 12 inserted screws had acceptable placement. Clinical signs of " lower " back pain resolved at 4 weeks after surgery. Diagnostic imaging and histopathology showed no bony spinal fusion of the LSJ. Force plate analysis revealed a trend toward improved pelvic limb function relative to preoperative function. Conclusions: PSRF of the LSJ of large breed dogs is technically possible. Improvements to the surgical technique to induce spinal fusion and assessment in a larger sample size are required before it can be recommended.
A nucleus pulposus prosthesis (NPP) made of the hydrogel N-vinyl-2-pyrrolidinone copolymerized wi... more A nucleus pulposus prosthesis (NPP) made of the hydrogel N-vinyl-2-pyrrolidinone copolymerized with 2-(4 0-iodobenzoyl)-oxo-ethyl methacrylate has recently been developed. The special features of this NPP, i.e. intrinsic radiopacity and its ability to swell in situ to fill the nucleus cavity and restore disc height, were investigated ex vivo in canine spinal specimens. L7-S1 intervertebral discs were isolated from three canine spinal specimens, and the dimensions of the nuclei pulposi were measured. Based on these averaged measurements, the NPP prototype was made and inserted in its dry form (xerogel) into a canine cadaveric spinal segment and allowed to swell overnight at 38 C. The integrity of the NPP and the filling of the nucleus cavity were assessed before and after swelling, using radiography, computed tomography, and magnetic resonance imaging. The ability of the NPP to restore disc height was assessed on radio-graphs of 10 spinal specimens. Thereafter the NPP was macroscopically assessed in situ by dissection of the spinal specimen. Both on imaging and macroscopically, 9/10 NPPs appeared to have a near perfect fit and disc height was restored in 8/10 spinal segments. The NPP may thus be an acceptable treatment option for low back patients meeting the requirements for NPP treatment.
Fingeroth/Advances in Intervertebral Disc Disease in Dogs and Cats, 2014
European Journal of Companion Animal Practice, 2012
Animal Genetics, 2010
Physical and linkage mapping of the bovine acidic a-glucosidase gene to chromosome 19 I Tammen1, ... more Physical and linkage mapping of the bovine acidic a-glucosidase gene to chromosome 19 I Tammen1, U Larsson1,5, N Bergknut1,5, W Barendse2, C Moran3, J A Dennis4 1 ReproGen, Centre for Advanced Technologies in Animal Genetics and Reproduction, Department of Veterinary Clinical Sciences, The University of Sydney, Camden, NSW 2570, Australia; 2 CSIRO, Tropical Agriculture, Gehrman Laboratories, University of Queensland, St
The Veterinary Journal, 2014
Veterinary Clinics of North America: Small Animal Practice, 2010
Degenerative lumbosacral stenosis (DLSS) is a common disorder seen mainly in large breed dogs. 1-... more Degenerative lumbosacral stenosis (DLSS) is a common disorder seen mainly in large breed dogs. 1-4 DLSS has been attributed many names over the past 40 years: cauda equina syndrome, cauda equina compression, lumbosacral stenosis or disease, lumbosacral instability, and DLSS. 2,4-8 All these terms refer to a degenerative disorder that is of multifactorial origin in which intervertebral disc (IVD) degeneration plays a major role. IVD degeneration, and bony and soft-tissue proliferations contribute to spinal stenosis and cauda equina compression leading to pain, lameness, and neurologic signs. This article describes current knowledge on the pathogenesis of IVD degeneration and recent advances in the management of DLSS. The biomechanics, pathogenesis, clinical manifestation, and treatments of lumbar disc herniation are very similar between dogs and humans. Hence many studies in humans with lumbar disc herniation can contribute to a better understanding of DLSS in dogs, and dogs may in turn be used as a spontaneous animal model for lumbar disc herniation in humans.
The Veterinary Journal, 2013
The relationship between intervertebral disc (IVD) disease and IVD degeneration remains unclear. ... more The relationship between intervertebral disc (IVD) disease and IVD degeneration remains unclear. The aim of the present study was to compare the clinical severity of IVD herniation (IVDH), determined with a neurological grading system, with findings of magnetic resonance imaging (MRI) and histology using grading systems for IVD degeneration in chondrodystrophic (CD; n = 37) and non-chondrodystrophic (NCD; n = 37) dogs. This study is the second part of a two-part investigation, where the first part involved the development and validation of a histological grading scheme for classification of canine IVD degeneration.
Animal Genetics, 2000
Fig. 2. Mendelian inheritance of IL12A intron 4 T stretch polymorphism in sheep. Alleles are show... more Fig. 2. Mendelian inheritance of IL12A intron 4 T stretch polymorphism in sheep. Alleles are shown on the right margin. Alleles are characterized by the following areas: open, allele 3; dotted, allele 5; filled, allele 6.
Het feline hyperesthesie syndroom (FHS) is een klinische manifestatie van plots optredend abnorma... more Het feline hyperesthesie syndroom (FHS) is een klinische manifestatie van plots optredend abnormaal gedrag waarbij de kat, onverwacht en onwillekeurig, een beeld kan laten zien van huidtrekkingen en spierkrampen. Het is geen specifieke ziekte maar een syndroom met een ruime differentiële diagnose (DD). De twee belangrijkste DD’s zijn dat het hier gaat om een paroxisme of compulsief gedrag. Andere oorza- ken die geopperd worden, zijn een focale epilep- sie, rugproblemen, huidproblemen, vlooien en/ of voedselallergieën. Het is een veel voorkomend probleem wat desondanks nauwelijks een fat- soenlijke wetenschappelijke bespreking kent. Er is dan ook maar weinig beschikbare literatuur.
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Papers by Niklas Bergknut