A new in vivo animal model to create intervertebral disc degeneration characterized by MRI, radiography, CT/discogram, biochemistry, and histology

Study Design. A new in vivo sheep model was developed that produced disc degeneration through the injection of 5-bromodeoxyuridine (BrdU) into the intervertebral disc. This process was studied using magnetic resonance imaging (MRI), radiography, CT/discogram, histology, and biochemistry. Objectives. To develop a sheep model of intervertebral disc degeneration that more faithfully mimics the pathologic hallmarks of human intervertebral disc degeneration. Summary of Background Data. Recent studies have shown age-related alterations in proteoglycan structure and organization in human intervertebral discs. An animal model that involves the use of age-related changes in disc cells can be beneficial over other more invasive degenerative models that involves directly damaging the matrix of disc tissue. Methods. Twelve sheep were injected with BrdU or vehicle (phosphate-buffered saline) into the central region of separate lumbar discs. Intact discs were used as controls. At the 2-, 6-, 10-, and 14-week time points, discs underwent MRI, radiography, histology, and biochemical analyses. A CT/discogram study was performed at the 14- week time point. Results. MRI demonstrated a progressive loss of T2-weighted signal intensity at BrdU-injected discs over the 14- week study period. Radiograph findings included osteophyte and disc space narrowing formed by 10 weeks post-BrdU treatment. CT discography demonstrated internal disc disruption in several BrdU-treated discs at the 14- week time point. Histology showed a progressive loss of the normal architecture and cell density of discs from the 2- week time point to the 14- week time point. A progressive loss of cell proliferation capacity, water content, and proteoglycans was also documented. Conclusions. BrdU injection into the central region of sheep discs resulted in degeneration of intervertebral discs. This progressive, degenerative process was confirmed using MRI, histology, and by observing changes in biochemistry. Degeneration occurred in a manner that was similar to that observed in human disc degeneration.