Spinal repair in immature animals: a novel approach using the South American opossum Monodelphis domestica.

Abstract

1. The adult mammalian central nervous system (CNS) is unable to regenerate following injury and repair has only been seen when implants of peripheral nervous tissue, fetal tissue or Schwann cells are used, or antibodies or trophic molecules applied. However, the immature mammalian CNS has revealed a capacity to repair without extrinsic influence. 2. The marsupial mammal provides a unique opportunity to access the immature CNS without invasive in utero surgery. In particular, the South American opossum Monodelphis domestica is an ideal animal for spinal cord injury studies examining the ability of the immature CNS to repair after injury. 3. The Monodelphis spinal cord may be examined for its response to injury either as an in vitro or in vivo system and, therefore, is a flexible model, allowing many different questions to be addressed by the most suitable approach. 4. The immature Monodelphis CNS was able to support fibre growth that reappeared 4 days after a crush at P3-P8 in vitro. Conduction was also restored at this time, accompanied by synaptic connections. 5. A cut lesion performed in vivo on Monodelphis spinal cords at P7 took longer to repair, with fibres reappearing across the injury site 2 weeks after the lesion; greater disruption to structure was noted both during early stages of repair and in adulthood. 6. Neural pathway tracing with dextran amine from the lumbar cord to the brain in adult Monodelphis, which received spinal lesions at P7, revealed a similar distribution of labelled cells in brainstem and mid-brain nuclei to that of control animals. 7. Studies of the locomotor behaviour of adult Monodelphis that had received either a cut or crush lesion at P7-P8 showed remarkably similar abilities to control animals when performing complex tasks. 8. The results of spinal cord injury studies with the immature Monodelphis CNS may help in the development of treatments for spinal injury patients.