Abstract

One major class of growth-inhibitory molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). These proteins are expressed throughout the developing and adult CNS and are associated with several growth-associated extracellular molecules. Following SCI in experimental animals, pharmacological interventions involving the degradation of lesion-induced CSPGs demonstrated a substantially enhanced regeneration of lesioned axons into and beyond the injury site and a significant functional recovery by treated animals. Experimental investigations into the role of individual members of the CSPG family revealed distinct expression patterns and functions in the traumatically injured CNS. We have performed a more detailed immunohistochemical investigation on the expression pattern of distinct members of the CSPG family, namely NG2, neurocan, versican and phosphacan in samples of post mortem human spinal cord, taken from patients who died at a range of survival times following severe traumatic SCI of the maceration type. The distribution pattern of individual members of the CSPG family varies significantly after human SCI. NG2 and phosphacan are both present in the evolving astroglial scar and might therefore play an important role in the blockade of successful CNS regeneration. Neurocan and versican are exclusively present in the lesion epicentre, associated with Schwann cells. They are present in the myelin sheaths of invading peripheral nerve fibres from lesioned dorsal roots and are not associated with regenerating CNS nerve fibres. As these results are not only in accordance with experimental studies but also reveal significant differences, they again point to the importance of correlative investigations in human post mortem tissue.

Highlights

  • A major class of axon growth-repulsive molecules associated with Central nervous system (CNS) scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs)

  • The spinal cords were removed from 4 control patients who had not suffered from any neurological disease (Table 1) and from 15 patients who died at a range of time points after traumatic spinal cord injury (Table 2)

  • In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells

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Summary

Introduction

A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). At the spinal cord lesion site, the initial damage to the parenchyma is followed by a complex cascade of secondary events including breakdown of the blood brain barrier (BBB), infiltration of blood-derived inflammatory cells, oedema, excitotoxicity and ischemia This early phase of secondary parenchymal damage is followed by the removal of tissue debris, resulting in fluid filled cystic cavitation and the deposition of extracellular matrix (ECM) proteins at the lesion epicentre [1]. Traumatic injuries which include damage to spinal nerve roots and the meninges induce fibroblast, meningeal cell and Schwann cell invasion into the lesion site [2,3,4] All these cell populations contribute to the production of a dense ECM that presents itself as a molecular barrier to axonal regeneration [1,3,5]

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