Elimination of basal lamina and the collagen "scar" after spinal cord injury fails to augment corticospinal tract regeneration

Exp Neurol. 1999 Nov;160(1):40-50. doi: 10.1006/exnr.1999.7200.

Abstract

The production of specific extracellular matrix molecules is upregulated following injury to the adult CNS, and some of these molecules have been postulated to inhibit axonal regeneration. In particular, the deposition of collagen in conjunction with basal lamina formation has been correlated with the failure of CNS axons to extend beyond sites of injury. In the present experiment, the spatial and temporal distribution of fibrillar collagen type III and the main constituents of basal lamina (collagen type IV and laminin) were characterized after defined lesions of the adult spinal cord at cervical and thoracic levels. The deposition of collagen was then blocked in animals undergoing defined mid-thoracic spinal cord lesions by administration of the iron chelator 2,2'-bipyridine, and subsequent effects on corticospinal axonal growth were examined. At time points from 1 to 6 weeks postinjury, collagen and laminin were deposited at spinal cord lesion sites as a dense matrix at the host-lesion interface that extended for short distances into the surrounding spinal cord parenchyma. The failure of corticospinal axons to grow beyond the lesioned region correlated spatially and temporally with collagen III formation and basal lamina production. However, successful blockade of collagen and basal lamina formation with 2,2'-bipyridine injections failed to enhance corticospinal axon regeneration or sprouting. These results suggest either that collagen and basal lamina formation after CNS injury do not contribute to corticospinal axonal growth failure or, more likely, that molecules in addition to collagen and basal lamina contribute to axonal growth failure and must be collectively blocked to promote corticospinal regeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2,2'-Dipyridyl / administration & dosage
  • 2,2'-Dipyridyl / pharmacology
  • 2,2'-Dipyridyl / therapeutic use*
  • Animals
  • Axons / pathology*
  • Basement Membrane / drug effects
  • Basement Membrane / pathology*
  • Cicatrix / prevention & control*
  • Collagen / analysis
  • Collagen / biosynthesis
  • Collagen / physiology*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / pathology*
  • Injections, Intralesional
  • Iron Chelating Agents / administration & dosage
  • Iron Chelating Agents / pharmacology
  • Iron Chelating Agents / therapeutic use*
  • Laminin / biosynthesis
  • Meninges / pathology
  • Nerve Regeneration*
  • Pyramidal Tracts / physiology*
  • Rats
  • Rats, Inbred F344
  • Spinal Cord Injuries / pathology*
  • Thoracic Vertebrae

Substances

  • Iron Chelating Agents
  • Laminin
  • 2,2'-Dipyridyl
  • Collagen