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NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury.

Buss A, Pech K, Kakulas BA, Martin D, Schoenen J, Noth J, Brook GA - BMC Neurol (2009)

Bottom Line: The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery.Neurocan staining was also associated with blood vessel walls.Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Aachen University Medical School, RWTH Aachen, Pauwelsstrasse 30, Germany. arminbuss@hotmail.com

ABSTRACT

Background: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid re-expression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord.

Methods: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type.

Results: In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells. The distribution patterns of phosphacan, neurocan and versican in control human spinal cord parenchyma were similar, with a fine reticular pattern being observed in white matter (but also located in gray matter for phosphacan). Neurocan staining was also associated with blood vessel walls. Furthermore, phosphacan, neurocan and versican were present in the myelin sheaths of ventral and dorsal nerve roots axons. After human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar. Neurocan and versican were detected exclusively in the lesion epicentre, being associated with infiltrating Schwann cells in the myelin sheaths of invading peripheral nerve fibres from lesioned dorsal roots.

Conclusion: NG2 and phosphacan were both present in the evolving astroglial scar and, therefore, might play an important role in the blockade of successful CNS regeneration. Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration. The present data points to the importance of such correlative investigations for demonstrating the clinical relevance of experimental data.

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The typical morphological appearance of the lesion site in severe human macerating SCI. Schematic diagrams showing the typical transverse appearance of the lesion site in the present cases of severe human traumatic SCI. A: At survival times ranging from 2 to 24 days after SCI, the lesion epicentre was characterised by the complete destruction of the cytoarchitecture and a massive hemorrhagic infiltration into the parenchyma (extent of hemorrhage indicated by stars). B: At survival times of 4 months and longer after SCI, the lesion epicentre was characterised by numerous regenerated root-like structures (small arrows) of variable sizes embedded in a dense ECM. Furthermore, individual spinal nerve roots (large arrows) and the entry zone of a nerve root into the spinal cord (asterisk) could be seen. C: When no cysts were present in the intermediate zone, the lesion was largely divided into an astrocytic scar and the region with nerve root-like structures, including Schwann cells (small arrows). D: In the intermediate zone, the lesion could often be sub-divided into a centrally located cystic region surrounded by an astrocytic scar (in this case in the ventral region) and an area with numerous small-medium root-like structures embedded in the ECM of the connective tissue scar (small arrows, in this case in the dorsal region). These schematic diagrams were prepared from representative sections and have been presented to provide a broad indication of where, within sections, particular images have been taken.
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Figure 4: The typical morphological appearance of the lesion site in severe human macerating SCI. Schematic diagrams showing the typical transverse appearance of the lesion site in the present cases of severe human traumatic SCI. A: At survival times ranging from 2 to 24 days after SCI, the lesion epicentre was characterised by the complete destruction of the cytoarchitecture and a massive hemorrhagic infiltration into the parenchyma (extent of hemorrhage indicated by stars). B: At survival times of 4 months and longer after SCI, the lesion epicentre was characterised by numerous regenerated root-like structures (small arrows) of variable sizes embedded in a dense ECM. Furthermore, individual spinal nerve roots (large arrows) and the entry zone of a nerve root into the spinal cord (asterisk) could be seen. C: When no cysts were present in the intermediate zone, the lesion was largely divided into an astrocytic scar and the region with nerve root-like structures, including Schwann cells (small arrows). D: In the intermediate zone, the lesion could often be sub-divided into a centrally located cystic region surrounded by an astrocytic scar (in this case in the ventral region) and an area with numerous small-medium root-like structures embedded in the ECM of the connective tissue scar (small arrows, in this case in the dorsal region). These schematic diagrams were prepared from representative sections and have been presented to provide a broad indication of where, within sections, particular images have been taken.

Mentions: The lesion sites of these severe human traumatic SCI cases could be sub-divided into the lesion epicentre and an intermediate zone. For a more detailed description, see Buss et al., 2007. Briefly, the lesion epicentre was initially characterised by the complete destruction of cytoarchitecture and massive haemorrhagic infiltration in between amorphous regions of tissue debris (Fig. 4A). At 24 days after injury, Schwann cell migration into the lesion core was seen, and in cases with longer survival times the lesion epicentre was characterised by a dense ECM with embedded nerve root-like structures and individual myelinated nerve fibres (Fig. 4B). However, no astrocytes were detectable in this region.


NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury.

Buss A, Pech K, Kakulas BA, Martin D, Schoenen J, Noth J, Brook GA - BMC Neurol (2009)

The typical morphological appearance of the lesion site in severe human macerating SCI. Schematic diagrams showing the typical transverse appearance of the lesion site in the present cases of severe human traumatic SCI. A: At survival times ranging from 2 to 24 days after SCI, the lesion epicentre was characterised by the complete destruction of the cytoarchitecture and a massive hemorrhagic infiltration into the parenchyma (extent of hemorrhage indicated by stars). B: At survival times of 4 months and longer after SCI, the lesion epicentre was characterised by numerous regenerated root-like structures (small arrows) of variable sizes embedded in a dense ECM. Furthermore, individual spinal nerve roots (large arrows) and the entry zone of a nerve root into the spinal cord (asterisk) could be seen. C: When no cysts were present in the intermediate zone, the lesion was largely divided into an astrocytic scar and the region with nerve root-like structures, including Schwann cells (small arrows). D: In the intermediate zone, the lesion could often be sub-divided into a centrally located cystic region surrounded by an astrocytic scar (in this case in the ventral region) and an area with numerous small-medium root-like structures embedded in the ECM of the connective tissue scar (small arrows, in this case in the dorsal region). These schematic diagrams were prepared from representative sections and have been presented to provide a broad indication of where, within sections, particular images have been taken.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2725028&req=5

Figure 4: The typical morphological appearance of the lesion site in severe human macerating SCI. Schematic diagrams showing the typical transverse appearance of the lesion site in the present cases of severe human traumatic SCI. A: At survival times ranging from 2 to 24 days after SCI, the lesion epicentre was characterised by the complete destruction of the cytoarchitecture and a massive hemorrhagic infiltration into the parenchyma (extent of hemorrhage indicated by stars). B: At survival times of 4 months and longer after SCI, the lesion epicentre was characterised by numerous regenerated root-like structures (small arrows) of variable sizes embedded in a dense ECM. Furthermore, individual spinal nerve roots (large arrows) and the entry zone of a nerve root into the spinal cord (asterisk) could be seen. C: When no cysts were present in the intermediate zone, the lesion was largely divided into an astrocytic scar and the region with nerve root-like structures, including Schwann cells (small arrows). D: In the intermediate zone, the lesion could often be sub-divided into a centrally located cystic region surrounded by an astrocytic scar (in this case in the ventral region) and an area with numerous small-medium root-like structures embedded in the ECM of the connective tissue scar (small arrows, in this case in the dorsal region). These schematic diagrams were prepared from representative sections and have been presented to provide a broad indication of where, within sections, particular images have been taken.
Mentions: The lesion sites of these severe human traumatic SCI cases could be sub-divided into the lesion epicentre and an intermediate zone. For a more detailed description, see Buss et al., 2007. Briefly, the lesion epicentre was initially characterised by the complete destruction of cytoarchitecture and massive haemorrhagic infiltration in between amorphous regions of tissue debris (Fig. 4A). At 24 days after injury, Schwann cell migration into the lesion core was seen, and in cases with longer survival times the lesion epicentre was characterised by a dense ECM with embedded nerve root-like structures and individual myelinated nerve fibres (Fig. 4B). However, no astrocytes were detectable in this region.

Bottom Line: The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery.Neurocan staining was also associated with blood vessel walls.Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Aachen University Medical School, RWTH Aachen, Pauwelsstrasse 30, Germany. arminbuss@hotmail.com

ABSTRACT

Background: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid re-expression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord.

Methods: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type.

Results: In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells. The distribution patterns of phosphacan, neurocan and versican in control human spinal cord parenchyma were similar, with a fine reticular pattern being observed in white matter (but also located in gray matter for phosphacan). Neurocan staining was also associated with blood vessel walls. Furthermore, phosphacan, neurocan and versican were present in the myelin sheaths of ventral and dorsal nerve roots axons. After human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar. Neurocan and versican were detected exclusively in the lesion epicentre, being associated with infiltrating Schwann cells in the myelin sheaths of invading peripheral nerve fibres from lesioned dorsal roots.

Conclusion: NG2 and phosphacan were both present in the evolving astroglial scar and, therefore, might play an important role in the blockade of successful CNS regeneration. Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration. The present data points to the importance of such correlative investigations for demonstrating the clinical relevance of experimental data.

Show MeSH
Related in: MedlinePlus