Abstract
Purpose: βII-tubulin, a regeneration-associated gene, is upregulated in injured peripheral neurons, but significantly less so in injured central neurons. Using a hamster dorsal spinal cord injury (SCI), the ability of single versus combinatorial treatment strategies to alter βII-tubulin mRNA expression in rubrospinal motoneurons (RSMN) was examined. We have shown that systemic testosterone propionate (TP) treatment in combination with peripheral nerve grafting into a SCI site produces a peripheral-like pattern of βII-tubulin mRNA expression in injured RSMN. In the present study, selected single- and combinatorial-therapy strategies were tested for their ability to promote a sustained upregulation of βII-tubulin mRNA levels in injured RSMN.
Methods: Single treatments of olfactory ensheathing cells (OEC), brain-derived neurotrophic factor (BDNF), or Schwann cells (SC) vs combinatorial treatments (SC + TP, OEC + TP, and OEC + BDNF) were administered to hamsters following a dorsal SCI. Quantitative in situ hybridization in conjunction with a βII-tubulin cDNA probe was accomplished.
Results: All of the single-therapy treatments tested were able to prevent the downregulation of βII-tubulin mRNA that occurred a week after injury alone, but only BDNF maintained high levels of βII-tubulin mRNA. In contrast, all combinatorial treatments tested maintained the upregulation of βII-tubulin mRNA expression in injured RSMN 1 week post-SCI.
Conclusions: Targeting both intrinsic and extrinsic components of CNS injury can re-program elements of the molecular response of injured central motoneurons.