Abstract
Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropuseugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P) days (P7-60) tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit. Results: Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180), the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch. Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions relevant to humans.
Highlights
Concentrated experimental efforts in adult animals, mainly rodents, have generated substantial information about spinal cord responses to injury and mechanisms behind axonal regenerative failure after trauma
Ethical approval The tammar wallaby (Macropus eugenii) pouch young (PY) were sourced from adult females derived from the CSIRO Wallaby Colony maintained at Crace, Canberra, Australia
All procedures were approved by the CSIRO Wildlife and Large Animal Animal Ethics Committee following National Health and Medical Research Council (NHMRC; Australia) guidelines
Summary
Concentrated experimental efforts in adult animals, mainly rodents, have generated substantial information about spinal cord responses to injury and mechanisms behind axonal regenerative failure after trauma. Translation into clinical outcomes for patients with spinal cord injuries (SCI) has been limited This is partly because of difficulties in replicating promising results (Steward et al, 2012), but mostly because of the lack of an accessible model to study therapies aimed at improving bipedal locomotion characteristics in humans. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropus eugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion Regulation of their muscle movements is more similar to humans than quadrupeds. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, Invited Reviewers version 1
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