Time course investigation of intervertebral disc degeneration produced by needle-stab injury of the rat caudal spine: laboratory investigation

J Neurosurg Spine. 2011 Oct;15(4):404-13. doi: 10.3171/2011.5.SPINE10811. Epub 2011 Jul 1.

Abstract

Object: In this study, the authors' goal was to investigate the long-term progression of disc degeneration and the participating mechanisms induced by needle puncture in a rat caudal disc model.

Methods: The C5-6 and C7-8 intervertebral discs of the caudal spine in rats were stabbed laterally using 21-gauge hypodermic needles to a depth of 5 mm from the subcutaneous surface with the aid of fluoroscopy. Signs of degeneration in the disc of the tail were analyzed from Day 1 to Week 30 by in vivo MR imaging, histology, and biochemical and/or molecular analyses.

Results: Magnetic resonance imaging showed a progressive decrease in T2 density and MR imaging index throughout the entire investigation, starting at Day 1 after the needle puncture. However, histological scores revealed a bimodal pattern, showing that severity increased in the first 17 days, declined thereafter, and increased again by 30 weeks. Gene expression analysis showed a transient up-regulation in gene expression of aggrecan, type II collagen, and BMP-2, and inhibition of type I collagen. The MMP-3 mRNA levels were up-regulated at all tested time points within 6 weeks postinjury. Furthermore, the degenerated disc did not recover spontaneously, as shown by decreases in T2 density, MR imaging index, and sulfated glycosaminoglycan content in conjunction with increases in histological scores at 15 and 30 weeks postsurgery.

Conclusions: This study demonstrates that needle puncture into a tail disc in the rat induces a rapid and progressive disc degeneration process without spontaneous recovery. Changes in gene expression profiles of the disc matrix molecules as well as anabolic and catabolic factors at early time points further delineate the mechanism of disc degeneration in this newly developed animal model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aggrecans / metabolism
  • Animals
  • Bone Morphogenetic Protein 2 / metabolism
  • Collagen Type II / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Intervertebral Disc / metabolism
  • Intervertebral Disc / pathology*
  • Intervertebral Disc Degeneration / metabolism
  • Intervertebral Disc Degeneration / pathology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Diseases / metabolism
  • Spinal Diseases / pathology*
  • Up-Regulation

Substances

  • Aggrecans
  • Bone Morphogenetic Protein 2
  • Collagen Type II