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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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Normal distribution of NG2, neurocan, versican and phosphacan in the human spinal cord. Transverse sections of control human spinal cords. A: NG2 immunohistochemistry reveals small stellate-shaped cells distributed homogeneously in white matter regions of human spinal cord (arrows). B: In the white matter, neurocan immunoreactivity is observed in the wall of a small blood vessel (arrow). Furthermore, a reticular staining pattern can be seen. C: In a dorsal nerve root, neurocan staining is present in myelin sheaths. D: Versican immunoreactivity is scattered in a dorsal nerve root and can be found in myelin sheaths of small diameter axons. E: Phosphacan immunohistochemistry reveals a fine reticular staining pattern in the gray matter. F: In a dorsal nerve root, phosphacan-immunopositive myelin rings can be observed. (A-F magnification × 320).
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Figure 2: Normal distribution of NG2, neurocan, versican and phosphacan in the human spinal cord. Transverse sections of control human spinal cords. A: NG2 immunohistochemistry reveals small stellate-shaped cells distributed homogeneously in white matter regions of human spinal cord (arrows). B: In the white matter, neurocan immunoreactivity is observed in the wall of a small blood vessel (arrow). Furthermore, a reticular staining pattern can be seen. C: In a dorsal nerve root, neurocan staining is present in myelin sheaths. D: Versican immunoreactivity is scattered in a dorsal nerve root and can be found in myelin sheaths of small diameter axons. E: Phosphacan immunohistochemistry reveals a fine reticular staining pattern in the gray matter. F: In a dorsal nerve root, phosphacan-immunopositive myelin rings can be observed. (A-F magnification × 320).

Mentions: In cervical, thoracic and lumbar segments of the normal, unlesioned spinal cord, NG2 immunoreactivity was restricted to small stellate-shaped cells (Fig. 2A). These cells were evenly distributed in both white and gray matter regions. Neurocan immunoreactivity in the spinal cord parenchyma was observed as a homogeneous, fine reticular pattern in the white matter. Furthermore, many small diameter blood vessels were stained for neurocan (Fig. 2B). In ventral and dorsal nerve roots the myelin sheaths were immunopositive (Fig. 2C). Similar to neurocan, versican immunoreactivity could also be found in a fine reticular pattern in the spinal cord white matter (not shown). In nerve roots, a scattered distribution pattern was detectable in myelin rings surrounding sub-populations of mostly small diameter axons (Fig. 2D). Immunohistochemistry for phosphacan showed a diffuse reticular pattern in both gray and white matter of control spinal cord (Fig. 2E). The staining pattern in ventral and dorsal nerve roots was identical to neurocan with immunoreactivity in myelin sheaths (Fig. 2F). The presence of CSPGs in peripheral myelin was supported by co-localisation with MBP (Fig. 3A). Furthermore, double immunofluorescence with laminin revealed a clear distinction between the CSPG-positive myelin rings and the laminin-positive endoneurium (Fig. 3B).


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)

Normal distribution of NG2, neurocan, versican and phosphacan in the human spinal cord. Transverse sections of control human spinal cords. A: NG2 immunohistochemistry reveals small stellate-shaped cells distributed homogeneously in white matter regions of human spinal cord (arrows). B: In the white matter, neurocan immunoreactivity is observed in the wall of a small blood vessel (arrow). Furthermore, a reticular staining pattern can be seen. C: In a dorsal nerve root, neurocan staining is present in myelin sheaths. D: Versican immunoreactivity is scattered in a dorsal nerve root and can be found in myelin sheaths of small diameter axons. E: Phosphacan immunohistochemistry reveals a fine reticular staining pattern in the gray matter. F: In a dorsal nerve root, phosphacan-immunopositive myelin rings can be observed. (A-F magnification × 320).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Normal distribution of NG2, neurocan, versican and phosphacan in the human spinal cord. Transverse sections of control human spinal cords. A: NG2 immunohistochemistry reveals small stellate-shaped cells distributed homogeneously in white matter regions of human spinal cord (arrows). B: In the white matter, neurocan immunoreactivity is observed in the wall of a small blood vessel (arrow). Furthermore, a reticular staining pattern can be seen. C: In a dorsal nerve root, neurocan staining is present in myelin sheaths. D: Versican immunoreactivity is scattered in a dorsal nerve root and can be found in myelin sheaths of small diameter axons. E: Phosphacan immunohistochemistry reveals a fine reticular staining pattern in the gray matter. F: In a dorsal nerve root, phosphacan-immunopositive myelin rings can be observed. (A-F magnification × 320).
Mentions: In cervical, thoracic and lumbar segments of the normal, unlesioned spinal cord, NG2 immunoreactivity was restricted to small stellate-shaped cells (Fig. 2A). These cells were evenly distributed in both white and gray matter regions. Neurocan immunoreactivity in the spinal cord parenchyma was observed as a homogeneous, fine reticular pattern in the white matter. Furthermore, many small diameter blood vessels were stained for neurocan (Fig. 2B). In ventral and dorsal nerve roots the myelin sheaths were immunopositive (Fig. 2C). Similar to neurocan, versican immunoreactivity could also be found in a fine reticular pattern in the spinal cord white matter (not shown). In nerve roots, a scattered distribution pattern was detectable in myelin rings surrounding sub-populations of mostly small diameter axons (Fig. 2D). Immunohistochemistry for phosphacan showed a diffuse reticular pattern in both gray and white matter of control spinal cord (Fig. 2E). The staining pattern in ventral and dorsal nerve roots was identical to neurocan with immunoreactivity in myelin sheaths (Fig. 2F). The presence of CSPGs in peripheral myelin was supported by co-localisation with MBP (Fig. 3A). Furthermore, double immunofluorescence with laminin revealed a clear distinction between the CSPG-positive myelin rings and the laminin-positive endoneurium (Fig. 3B).

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