Novel combination strategies to repair the injured mammalian spinal cord

Mary B Bunge

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Due to the varied and numerous changes in spinal cord tissue following injury, successful treatment for repair may involve strategies combining neuroprotection (pharmacological prevention of some of the damaging intracellular cascades that lead to secondary tissue loss), axonal regeneration promotion (cell transplantation, genetic engineering to increase growth factors, neutralization of inhibitory factors, reduction in scar formation), and rehabilitation. Our goal has been to find effective combination strategies to improve outcome after injury to the adult rat thoracic spinal cord. Combination interventions tested have been implantation of Schwann cells (SCs) plus neuroprotective agents and growth factors administered in various ways, olfactory ensheathing cell (OEC) implantation, chondroitinase addition, or elevation of cyclic AMP. The most efficacious strategy in our hands for the acute complete transection/SC bridge model, including improvement in locomotion [Basso, Beattie, Bresnahan Scale (BBB)], is the combination of SCs, OECs, and chondroitinase administration (BBB 2.1 vs 6.6, 3 times more myelinated axons in the SC bridge, increased serotonergic axons in the bridge and beyond, and significant correlation between the number of bridge myelinated axons and functional improvement). We found the most successful combination strategy for a subacute spinal cord contusion injury (12.5-mm, 10-g weight, MASCIS impactor) to be SCs and elevation of cyclic AMP (BBB 10.4 vs 15, significant increases in white matter sparing, in myelinated axons in the implant, and in responding reticular formation and red and raphe nuclei, and a significant correlation between the number of serotonergic fibers and improvement in locomotion). Thus, in two injury paradigms, these combination strategies as well as others studied in our laboratory have been found to be more effective than SCs alone and suggest ways in which clinical application may be developed.

Original languageEnglish
Pages (from-to)262-269
Number of pages8
JournalJournal of Spinal Cord Medicine
Volume31
Issue number3
StatePublished - Sep 8 2008

Fingerprint

Schwann Cells
Spinal Cord
Axons
Chondroitinases and Chondroitin Lyases
Locomotion
Spinal Cord Injuries
Cyclic AMP
Wounds and Injuries
Red Nucleus
Raphe Nuclei
Reticular Formation
Genetic Engineering
Cell Transplantation
Neuroprotective Agents
Cicatrix
Regeneration
Intercellular Signaling Peptides and Proteins
Thorax
Rehabilitation
Pharmacology

Keywords

  • Axonal regeneration
  • Chondroitinase
  • Cyclic adenosine monophosphate
  • Olfactory ensheathing cells
  • Schwann cells
  • Spinal cord injuries

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Novel combination strategies to repair the injured mammalian spinal cord. / Bunge, Mary B.

In: Journal of Spinal Cord Medicine, Vol. 31, No. 3, 08.09.2008, p. 262-269.

Research output: Contribution to journalArticle

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