Peripheral Nerve Grafts Support Regeneration after Spinal Cord Injury

Abstract

Summary: Traumatic insults to the spinal cord induce both immediate mechanical damage and subsequent tissue degeneration leading to a substantial physiological, biochemical, and functional reorganization of the spinal cord. Various spinal cord injury (SCI) models have shown the adaptive potential of the spinal cord and its limitations in the case of total or partial absence of supraspinal influence. Meaningful recovery of function after SCI will most likely result from a combination of therapeutic strategies, including neural tissue transplants, exogenous neurotrophic factors, elimination of inhibitory molecules, functional sensorimotor training, and/or electrical stimulation of paralyzed muscles or spinal circuits. Peripheral nerve grafts provide a growthpermissive substratum and local neurotrophic factors to enhance the regenerative effort of axotomized neurons when grafted into the site of injury. Regenerating axons can be directed via the peripheral nerve graft toward an appropriate target, but they fail to extend beyond the distal graft-host interface because of the deposition of growth inhibitors at the site of SCI. One method to facilitate the emergence of axons from a graft into the spinal cord is to digest the chondroitin sulfate proteoglycans that are associated with a glial scar. Importantly, regenerating axons that do exit the graft are capable of forming functional synaptic contacts. These results have been demonstrated in acute injury models in rats and cats and after a chronic injury in rats and have important implications for our continuing efforts to promote structural and functional repair after SCI.

Bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells: Case series of 14 patients

“…[35][36][37][38][39][40][41][42] Axons growing within peripheral nerve grafts have been found to retain their physiological properties 43 and to make functional synapses with neurons near their point of CNS re-entry. 44 In a clinical study, 13 three segments from autologous sural In the current study, the spinal cord defect has been bridged by sural nerve side grafts placed in a subpial manner.…”

“…46,48,94,95 These include myelin inhibitors (Nogo-A, MAG108 (myelin-associated glycoprotein), and OMgp109 (oligodendrocyte myelin glycoprotein)); chondroitin sulfate proteoglycans (neurocan, versican, aggrecan, brevican, phosphacan, and NG2); semaphorins; and ephrins. Future efforts should therefore be directed to more lysis of these proteoglycans by adding chondroitinase ABC microinjection systems 42,96,97 ; this should be thermostabilized beforehand. 98 Furthermore, evidence points to the superiority of Type I versus Type II astrocytes in migrating into host tissue and mixing with host glia while suppressing scar formation, and in promoting regeneration of sensory axons and improving locomotor function.…”

Molecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair

“…To regain voluntary motor function of fingers, hands, arms and legs, the regeneration of damaged descending cortical and brainstem axons involved in motor function needs to occur, including remyelination and re-establishing synaptic connections with target neurons (Côté et al 2011;Smith et al 2012). If the newly formed connections are not suitable for generating proper functional movements, they may be recruited for such through the implementation of targeted rehabilitative strategies.…”

Editorial

“…In their studies, grafted peripheral nerve segments were used to provide an axon growth permissive environment and to avoid the nonpermissive spinal cord. Since then, these peripheral nerve graft findings have been extended, as described in the article by Côté, Amin, Tom, and Houle, [24]. Moreover, a variety of other axon growth permissive environments have been identified, including peripheral nerve Schwann cells, olfactory ensheathing glia, fetal tissue, stem cells, precursor cells, progenitor cells, marrow stromal cells, and reactive macrophages used alone, combined, and in biomaterials.…”

“…Two extremely important issues that have arisen from experimental studies, and in some cases, clinical studies of these tissues and cells are 1) the modest axon growth into the permissive environments, and 2) the unwillingness of regenerated axons to exit them and re-enter the spinal cord. Côté, Amin, Tom, and Houle, in their article [24], discuss an approach that they found to be successful for dealing with the latter issue. This involves digesting inhibitory chondroitin sulfate proteoglycans that are present at the end of the peripheral nerve graft, and within the glial scar, with chondroitinase ABC (ChABC).…”