Sprouting, regeneration and circuit formation in the injured spinal cord: factors and activity

Abstract

Central nervous system (CNS) injuries are particularly traumatic, owing to the limited capabilities of the mammalian CNS for repair. Nevertheless, functional recovery is observed in patients and experimental animals, but the degree of recovery is variable. We review the crucial characteristics of mammalian spinal cord function, tract development, injury and the current experimental therapeutic approaches for repair. Regenerative or compensatory growth of neurites and the formation of new, functional circuits require spontaneous and experimental reactivation of developmental mechanisms, suppression of the growth-inhibitory properties of the adult CNS tissue and specific targeted activation of new connections by rehabilitative training.

Molecular/genetic manipulation of extrinsic axon guidance factors for CNS repair and regeneration

“…Still, little is known about the accuracy in reconstruction of damaged circuits with functional indices being the final arbiter for circuit repair. Likewise, functional recovery is most likely due to the formation of novel circuits from sprouting and regenerating axons that undergo regional as well as supraspinal plasticity and rarely reconstruction of the original circuit (Maier and Schwab, 2006). During development, axon pathfinding and target recognition are guided by both positive (permissive and attractive) and negative (inhibitory and repulsive) cues, which operate at shortor long-range (Tessier-Lavigne and Goodman, 1996).…”

Chondroitinase ABC Combined with Neurotrophin NT-3 Secretion and NR2D Expression Promotes Axonal Plasticity and Functional Recovery in Rats with Lateral Hemisection of the Spinal Cord

“…Among these therapies, blockade of inhibitory NogoA (Maier and Schwab, 2006), digestion of chondroitin sulfate proteoglycans (CSPGs) , neurotrophin delivery (Lu and Tuszynski, 2008), intervention in axon growth signaling pathways (Shearer et al, 2003) and physical rehabilitation (Girgis et al, 2007), have been shown to promote regeneration and/or sprouting of damaged and undamaged axons leading to functional repair. However, none of these interventions by itself gives full recovery of function.…”

Plastic Changes in Lumbar Locomotor Networks after a Partial Spinal Cord Injury in Cats

“…First, descending inputs were transmitted via crossed pathways to reach the left side. Functional recovery with an increased connectivity via crossed pathways after SCI have been reported before, including the brainstem (Matsuyama et al, 2004;Maier and Schwab, 2006;van den Brand et al, 2012;Filli et al, 2014;Zörner et al, 2014). Second, the disconnection from the ipsilateral descending pathways for 3 weeks may have induced an intrinsic spinal plasticity resulting in more autonomous activation of the CPG, a situation comparable to the adaptation after a chronic complete spinal cord section (De Leon et al, 1998;Lavrov et al, 2006;.…”

“…In contrast to reorganization within cortical or subcortical sensory and motor representation areas after SCI, our knowledge about plasticity below the lesion remains limited (Maier and Schwab, 2006;Zörner et al, 2014). A functional recovery can be seen after a lateral hemisection of the spinal cord and this model has been used in several studies to evaluate underlying changes due to disconnection from supraspinal tracts on the lesion side compared with the "intact" side (Murray and Goldberger, 1974;Little et al, 1988;Kunkel-Bagden et al, 1992;Helgren and Goldberger, 1993;Michele Basso, et al, 1994;Muir et al, 1998;Babu and Namasivayam, 2008;Doperalski et al, 2011).…”