Arrested development of the dorsal column following neonatal spinal cord injury in the opossum, Monodelphis domestica

Abstract

Developmental studies of spinal cord injury in which regrowth of axons occurs across the site of transection rarely distinguish between the recovery of motor-controlling pathways and that of ascending axons carrying sensory information. We describe the morphological changes that occur in the dorsal column (DC) of the grey short-tailed opossum, Monodelphis domestica, following spinal cord injury at two early developmental ages. The spinal cords of opossums that had had their mid-thoracic spinal cords completely transected at postnatal day 7 (P7) or P28 were analysed. Profiles of neurofilament immunoreactivity in transected cords showing DC development were differentially affected by the injury compared with the rest of the cord and cytoarchitecture was modified in an age- and site-dependent manner. The ability of DC neurites to grow across the site of transection was confirmed by injection of fluorescent tracer below the injury. P7 transected cords showed labelling in the DC above the site of original transection indicating that neurites of this sensory tract were able to span the injury. No growth of any neuronal processes was seen after P28 transection. Thus, DC is affected by spinal injury in a differential manner depending on the age at which the transection occurs. This age-differential response, together with other facets of remodelling that occur after neonatal spinal injury, might explain the locomotor adaptations and recovery observed in these animals.

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

“…This approach successfully identified broad statistically significant decreases in the expression of neural progenitor and neural stem cell–related genes and increases in expression of markers of spinal cord maturation (myelination, mature neurons and glia) during development (Figure 6b). These gene changes are not surprising given that the cord is developing rapidly during this time resulting in approximately a fivefold increase in number of descending axons (Fry et al, 2003) and an approximate doubling in the cross‐sectional area of the spinal cord during this developmental period (Wheaton et al, 2015). These developmental findings are consistent with our chosen methodology being sufficiently robust and having the capacity to identify biologically relevant and important gene expression changes.…”

“…Cords were collected for RNA sequencing analysis +1, +3 or +7 days later, along with age‐matched control tissues. Detailed procedures for completely transecting the lower thoracic (T10) spinal cord in these pups have been described previously (Wheaton et al, 2011; Wheaton et al, 2013; Wheaton, Noor, Dziegielewska, Whish, & Saunders, 2015). Briefly, opossum pups were anesthetized to a surgical level using inhaled isoflurane (3% in O 2 ‐enriched air), either while still attached at the teat to the anesthetized mother (in the case of P7SCI pups) or individually (in the case of the more mature P28SCI pups).…”

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

“…Previous studies have used the marsupial South American opossum ( Monodelphis domestica ) and North American opossum ( Didelphis virginiana ) to demonstrate the effects of spinal cord injuries at different stages of development ( Fry & Saunders, 2000; Martin & Xu, 1988; Saunders et al , 1989; Saunders et al , 1998; Wang et al , 1996; Wang et al , 1998 a ; Wheaton et al , 2011; Wheaton et al , 2013; Wheaton et al , 2015; Xu & Martin, 1992). It has been shown that when pups were injured early in development at post-natal day P7, regrowth of supraspinal neuronal axons across the lesion site was demonstrated (termed the “permissive” stage, as previously suggested for the period when functional repair occurred in chick embryonic spinal cord following SCI; Keirstead et al , 1992).…”

“…Terman et al , 1999; Wang et al , 1998 a ). Several attempts have been made to identify cellular and molecular changes that could explain this shift in the ability of axons to bridge the site of injury ( Noor et al , 2011; Saunders et al , 1998; Saunders et al , 2014; Terman et al , 1999; Wang et al , 1998 b ; Wheaton et al , 2015) and some suggestions that it could be related to the onset of myelination were also put forward ( Bandtlow, 2003; Saunders et al , 2014; Wheaton et al , 2015). …”

A three-dimensional stereotaxic atlas of the gray short-tailed opossum (Monodelphis domestica) brain

“… 2014 ) or spinal cord injury treatment (Wheaton et al. 2015 ). Moreover, after sequencing its genome by Mikkelsen et al.…”