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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 cellular and molecular composition of the scar following human SCI at both early and long survival times. Transverse sections of the human spinal cord of patients with survival times of 10 to 24 days after SCI. The schematic diagrams in the upper right corner indicate the region of the section from which images were prepared (black rectangle). A: Ten days after SCI, NG2 staining demonstrated round to oval-shaped cells at the lesion epicentre (arrows). B: In sections from the lesion site of the same case, neurocan immunoreactivity revealed myelin staining in a dorsal nerve root that stopped abruptly at the dorsal root entry zone. C: Eleven days after SCI, NG2 staining in the intermediate zone demonstrated cells with a round to oval morphology (arrows) and small stellate-shaped cells (arrowheads). D: In the same section, higher magnification better illustrated the stellate-shaped morphology of oligodendrocyte precursor cells (arrows). E: Twenty-four days after SCI, phosphacan staining was present on myelin rings of some axonal structures close to the lesion epicentre. F: In sections from the intermediate zone of the same case, GFAP immunohistochemistry revealed a dense network of irregular fibres without identifiable cell bodies in between. G-H: In near adjacent sections from the intermediate zone, NG2 (G) and phosphacan (H) staining revealed similar distributions, with a dense, irregular network of fibres and no clearly identifiable immunoreactive cell bodies. (A-C and E-H magnification × 320, D magnification × 640).
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Figure 5: The cellular and molecular composition of the scar following human SCI at both early and long survival times. Transverse sections of the human spinal cord of patients with survival times of 10 to 24 days after SCI. The schematic diagrams in the upper right corner indicate the region of the section from which images were prepared (black rectangle). A: Ten days after SCI, NG2 staining demonstrated round to oval-shaped cells at the lesion epicentre (arrows). B: In sections from the lesion site of the same case, neurocan immunoreactivity revealed myelin staining in a dorsal nerve root that stopped abruptly at the dorsal root entry zone. C: Eleven days after SCI, NG2 staining in the intermediate zone demonstrated cells with a round to oval morphology (arrows) and small stellate-shaped cells (arrowheads). D: In the same section, higher magnification better illustrated the stellate-shaped morphology of oligodendrocyte precursor cells (arrows). E: Twenty-four days after SCI, phosphacan staining was present on myelin rings of some axonal structures close to the lesion epicentre. F: In sections from the intermediate zone of the same case, GFAP immunohistochemistry revealed a dense network of irregular fibres without identifiable cell bodies in between. G-H: In near adjacent sections from the intermediate zone, NG2 (G) and phosphacan (H) staining revealed similar distributions, with a dense, irregular network of fibres and no clearly identifiable immunoreactive cell bodies. (A-C and E-H magnification × 320, D magnification × 640).

Mentions: In the present post mortem cases, the lesion epicentre was characterised by the complete destruction of cytoarchitecture. From 2–8 days after trauma, no specific staining for NG2, neurocan, versican or phosphacan could be detected in this area (not shown). At 10 and 11 days after SCI, immunohistochemistry for NG2 revealed cells with a round to oval morphology at the lesion core (Fig. 5A). Subsequent double immunofluorescence demonstrated that these cells were macrophages (Fig. 3C). It was not possible to determine if these cells actually expressed NG2 or were immunoreactive due to phagocytosis of NG2-containing debris from the lesioned parenchyma.


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 cellular and molecular composition of the scar following human SCI at both early and long survival times. Transverse sections of the human spinal cord of patients with survival times of 10 to 24 days after SCI. The schematic diagrams in the upper right corner indicate the region of the section from which images were prepared (black rectangle). A: Ten days after SCI, NG2 staining demonstrated round to oval-shaped cells at the lesion epicentre (arrows). B: In sections from the lesion site of the same case, neurocan immunoreactivity revealed myelin staining in a dorsal nerve root that stopped abruptly at the dorsal root entry zone. C: Eleven days after SCI, NG2 staining in the intermediate zone demonstrated cells with a round to oval morphology (arrows) and small stellate-shaped cells (arrowheads). D: In the same section, higher magnification better illustrated the stellate-shaped morphology of oligodendrocyte precursor cells (arrows). E: Twenty-four days after SCI, phosphacan staining was present on myelin rings of some axonal structures close to the lesion epicentre. F: In sections from the intermediate zone of the same case, GFAP immunohistochemistry revealed a dense network of irregular fibres without identifiable cell bodies in between. G-H: In near adjacent sections from the intermediate zone, NG2 (G) and phosphacan (H) staining revealed similar distributions, with a dense, irregular network of fibres and no clearly identifiable immunoreactive cell bodies. (A-C and E-H magnification × 320, D magnification × 640).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: The cellular and molecular composition of the scar following human SCI at both early and long survival times. Transverse sections of the human spinal cord of patients with survival times of 10 to 24 days after SCI. The schematic diagrams in the upper right corner indicate the region of the section from which images were prepared (black rectangle). A: Ten days after SCI, NG2 staining demonstrated round to oval-shaped cells at the lesion epicentre (arrows). B: In sections from the lesion site of the same case, neurocan immunoreactivity revealed myelin staining in a dorsal nerve root that stopped abruptly at the dorsal root entry zone. C: Eleven days after SCI, NG2 staining in the intermediate zone demonstrated cells with a round to oval morphology (arrows) and small stellate-shaped cells (arrowheads). D: In the same section, higher magnification better illustrated the stellate-shaped morphology of oligodendrocyte precursor cells (arrows). E: Twenty-four days after SCI, phosphacan staining was present on myelin rings of some axonal structures close to the lesion epicentre. F: In sections from the intermediate zone of the same case, GFAP immunohistochemistry revealed a dense network of irregular fibres without identifiable cell bodies in between. G-H: In near adjacent sections from the intermediate zone, NG2 (G) and phosphacan (H) staining revealed similar distributions, with a dense, irregular network of fibres and no clearly identifiable immunoreactive cell bodies. (A-C and E-H magnification × 320, D magnification × 640).
Mentions: In the present post mortem cases, the lesion epicentre was characterised by the complete destruction of cytoarchitecture. From 2–8 days after trauma, no specific staining for NG2, neurocan, versican or phosphacan could be detected in this area (not shown). At 10 and 11 days after SCI, immunohistochemistry for NG2 revealed cells with a round to oval morphology at the lesion core (Fig. 5A). Subsequent double immunofluorescence demonstrated that these cells were macrophages (Fig. 3C). It was not possible to determine if these cells actually expressed NG2 or were immunoreactive due to phagocytosis of NG2-containing debris from the lesioned parenchyma.

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