In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration
ABSTRACT Introduction Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be con...
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/jsp2.70076 |
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| author | Karthikeyan Rajagopal Thomas P. Schaer Kyle D. Meadows Madeline Boyes Rachel Hilliard John C. O'Donnell George R. Dodge Dmitriy Petrov Dawn M. Elliott Robert L. Mauck Lachlan J. Smith Neil R. Malhotra |
| author_facet | Karthikeyan Rajagopal Thomas P. Schaer Kyle D. Meadows Madeline Boyes Rachel Hilliard John C. O'Donnell George R. Dodge Dmitriy Petrov Dawn M. Elliott Robert L. Mauck Lachlan J. Smith Neil R. Malhotra |
| author_sort | Karthikeyan Rajagopal |
| collection | DOAJ |
| description | ABSTRACT Introduction Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be contributing factors. A comprehensive understanding of this microenvironment, including changes in nutrient availability as a function of degeneration, is critical for the development of effective cell‐based treatments. The goal of this study was to adapt brain tissue oxygen probes and microdialysis catheters for in situ determination of relative NP oxygen, glucose, and lactate levels in a preclinical goat model of disc degeneration. Methods Following ex vivo technical refinement in bovine caudal discs, baseline metabolite measurements were performed in vivo in the lumbar discs of 3 large frame goats. Degeneration was then induced via injection of chondroitinase ABC (ChABC) into the NP, and measurements were repeated after 12 weeks. Degeneration severity was graded using magnetic resonance imaging (MRI) and histology, and vertebral endplate porosity was assessed using microcomputed tomography. Results Oxygen and lactate levels in goat NPs were significantly higher in degenerate compared to healthy discs, while glucose levels were not significantly different. ChABC‐injected discs exhibited higher vertebral endplate porosity, worse histological and MRI grades, and a spectrum of cartilage endplate damage compared to healthy discs. There were significant positive correlations between MRI grade and both NP oxygen and lactate levels. Discussion We successfully adapted techniques including surgical placement, equilibration time, flow rate, and detection method for in situ measurement of oxygen, glucose, and lactate in a goat model of disc degeneration. Interestingly, while increased lactate with degeneration was expected, increased oxygen levels were unexpected. Our findings may, in part, be explained by associated alterations in disc and endplate structure, and motivate future studies to comprehensively establish the underlying mechanisms in this model. |
| format | Article |
| id | doaj-art-b1710ea86fb74641b3397c1a9f1c29b3 |
| institution | Matheson Library |
| issn | 2572-1143 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | JOR Spine |
| spelling | doaj-art-b1710ea86fb74641b3397c1a9f1c29b32025-06-26T15:30:52ZengWileyJOR Spine2572-11432025-06-0182n/an/a10.1002/jsp2.70076In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc DegenerationKarthikeyan Rajagopal0Thomas P. Schaer1Kyle D. Meadows2Madeline Boyes3Rachel Hilliard4John C. O'Donnell5George R. Dodge6Dmitriy Petrov7Dawn M. Elliott8Robert L. Mauck9Lachlan J. Smith10Neil R. Malhotra11Translational Musculoskeletal Research Center Corporal Michael J. Crescenz VA Medical Center Philadelphia Pennsylvania USATranslational Musculoskeletal Research Center Corporal Michael J. Crescenz VA Medical Center Philadelphia Pennsylvania USADepartment of Biomedical Engineering University of Delaware Newark Delaware USADepartment of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania Kennett Square Pennsylvania USADepartment of Clinical Studies New Bolton Center, School of Veterinary Medicine, University of Pennsylvania Kennett Square Pennsylvania USADepartment of Neurosurgery Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USADepartment of Orthopaedic Surgery Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USADepartment of Neurosurgery Perelman School of Medicine, University of Pennsylvania Philadelphia Pennsylvania USADepartment of Biomedical Engineering University of Delaware Newark Delaware USATranslational Musculoskeletal Research Center Corporal Michael J. Crescenz VA Medical Center Philadelphia Pennsylvania USATranslational Musculoskeletal Research Center Corporal Michael J. Crescenz VA Medical Center Philadelphia Pennsylvania USATranslational Musculoskeletal Research Center Corporal Michael J. Crescenz VA Medical Center Philadelphia Pennsylvania USAABSTRACT Introduction Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be contributing factors. A comprehensive understanding of this microenvironment, including changes in nutrient availability as a function of degeneration, is critical for the development of effective cell‐based treatments. The goal of this study was to adapt brain tissue oxygen probes and microdialysis catheters for in situ determination of relative NP oxygen, glucose, and lactate levels in a preclinical goat model of disc degeneration. Methods Following ex vivo technical refinement in bovine caudal discs, baseline metabolite measurements were performed in vivo in the lumbar discs of 3 large frame goats. Degeneration was then induced via injection of chondroitinase ABC (ChABC) into the NP, and measurements were repeated after 12 weeks. Degeneration severity was graded using magnetic resonance imaging (MRI) and histology, and vertebral endplate porosity was assessed using microcomputed tomography. Results Oxygen and lactate levels in goat NPs were significantly higher in degenerate compared to healthy discs, while glucose levels were not significantly different. ChABC‐injected discs exhibited higher vertebral endplate porosity, worse histological and MRI grades, and a spectrum of cartilage endplate damage compared to healthy discs. There were significant positive correlations between MRI grade and both NP oxygen and lactate levels. Discussion We successfully adapted techniques including surgical placement, equilibration time, flow rate, and detection method for in situ measurement of oxygen, glucose, and lactate in a goat model of disc degeneration. Interestingly, while increased lactate with degeneration was expected, increased oxygen levels were unexpected. Our findings may, in part, be explained by associated alterations in disc and endplate structure, and motivate future studies to comprehensively establish the underlying mechanisms in this model.https://doi.org/10.1002/jsp2.70076caprineendplatelumbarmetabolitesmicrodialysisnutrition |
| spellingShingle | Karthikeyan Rajagopal Thomas P. Schaer Kyle D. Meadows Madeline Boyes Rachel Hilliard John C. O'Donnell George R. Dodge Dmitriy Petrov Dawn M. Elliott Robert L. Mauck Lachlan J. Smith Neil R. Malhotra In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration JOR Spine caprine endplate lumbar metabolites microdialysis nutrition |
| title | In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration |
| title_full | In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration |
| title_fullStr | In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration |
| title_full_unstemmed | In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration |
| title_short | In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration |
| title_sort | in vivo measurements reveal increased nucleus pulposus lactate and oxygen concentrations in a goat model of intervertebral disc degeneration |
| topic | caprine endplate lumbar metabolites microdialysis nutrition |
| url | https://doi.org/10.1002/jsp2.70076 |
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