A bipedal mammalian model for spinal cord injury research: The tammar wallaby

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 (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. 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.

Case Report: Unable to Jump Like a Kangaroo Due to Myositis Ossificans Circumscripta

“…In contrast to the described kangaroo with lumbar MO, MO has rarely been described in the lumbar musculature in humans (31). Due to their vertically oriented vertebral column, kangaroos are often used as an animal model for human vertebral column diseases to describe biomechanical properties and treatment options (34)(35)(36). Nevertheless, there are major differences in the anatomy of humans and kangaroos (34,35).…”

“…Due to their vertically oriented vertebral column, kangaroos are often used as an animal model for human vertebral column diseases to describe biomechanical properties and treatment options (34)(35)(36). Nevertheless, there are major differences in the anatomy of humans and kangaroos (34,35). Especially, the lumbar spinal processes are much bigger in kangaroos than in humans (22).…”

Identification of regenerative processes in neonatal spinal cord injury in the opossum (Monodelphis domestica): A transcriptomic study

“…This robust regrowth after early‐age injury is maintained through to adulthood and has been demonstrated in the gray short‐tailed opossum ( Monodelphis domestica ; Saunders et al, 1992; Saunders et al, 1995), the North American opossum ( Didelphis virginiana ; Martin, Terman, & Wang, 2000; X. M. Wang, Terman, & Martin, 1996) and the tammar wallaby ( Macropus eugenii ; Saunders et al, 2017). In all three species it is accompanied by supraspinally mediated functional recovery of coordinated hindlimb locomotion by adulthood (Saunders et al, 1998; Saunders et al, 2017; X. M. Wang, Basso, Terman, Bresnahan, & Martin, 1998; Wheaton et al, 2011; Wheaton et al, 2013). The regenerative response diminishes if injuries are made later in development (Lane et al, 2007) until no regrowth occurs, similar to adult injuries (Wheaton et al, 2011).…”

Evaluating Gait and Locomotion in Rodents with the CatWalk

“…As prey animals, it has been proposed that they are evolutionarily conditioned to hide disability and pain (Mogil, 2015) and can compensate for injury with their quadrupedal stature in ways bipedal humans cannot. For example, quadrupeds can shift their weight to their forelimbs in the case of a hindlimb injury, where bipeds are unable to do so (Saunders et al, 2017). As such, some motor deficits may not be as easily detected in rodents as they are in humans.…”