Bridging Defects in Chronic Spinal Cord Injury Using Peripheral Nerve Grafts: From Basic Science to Clinical Experience

Abstract

Nerve grafting of the injured spinal cord should pursue a sixfold attack: lysing the fibrosis/gliosis to an extent that allows settling of the basal lamina preventing meanwhile collapse of the neural tissue matrix; supplying the tissue matrix with a suitable scaffold, on which the basal lamina can settle; basal lamina synthesis; seeding the basal lamina with cell adhesion molecules; providing the axonal growth cone with neurite outgrowth promoting factors that allow its distal progression; supplying the axonal growth cone with neurotrophic factors that power its continued growth. In addition to this, the intrinsic properties of the neurons should be stimulated, possibly through modulating the function of astrocytes by heparin, aspirin and other factors. Nerve side grafting of the cord increases the incidence of nerve regeneration by applying additional grafts extending from the side of the donor end of the cord to the side of the recipient end. Also, it allows the surgeon to enhance regeneration through a partially regenerated cord. During surgery, after establishment of CSF circulation, a long-lasting indwelling catheter has to be inserted for postoperative drug and cell delivery. This allows for continual lysis of the gliosis by chondroitinase ABC, sialidase and other factors.

Speculations on the Use of Marine Polysaccharides as Scaffolds for Artificial Nerve ‘Side-’Grafts

“…This can take place through a continous cell and drug delivery system (catheter) [81,82]. Versatility is required to achieve the following three aims simultaneously: keeping the cell and drug delivery system (catheter) patent; dissolving the fibrous tissue that blocks pores after release of molecules and cells and replenishment of released molecules and cells associated with preservation of their spatial concentration gradients.…”

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

“…There is an emerging role of heparin in lysing of the gliosis, as reviewed elsewhere [39]. Both unfractionated and low molecular weight heparins have a fibrolytic (gliolytic) effect, can modulate astrocyte function and are used as lumen fillers.…”

“…This can take place through an intrathecal (possibly extradural) continuous cell and drug delivery system (catheter) [39,209]. Catheter-related complications include tension headache, meningitis, fibrous track formation, catheter slippage, difficult catheter insertion and catheter blockage.…”