 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, October 18, 2006, 26(42):10856-10867; doi:10.1523/JNEUROSCI.2980-06.2006
Previous Article | Next Article
Development/Plasticity/Repair
Chondroitinase ABC Promotes Sprouting of Intact and Injured Spinal Systems after Spinal Cord Injury
A. W. Barritt, * M. Davies, * F. Marchand, R. Hartley, J. Grist, P. Yip, S. B. McMahon, andE. J. Bradbury Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, United Kingdom
Correspondence should be addressed to Dr. Elizabeth J. Bradbury, Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London Bridge, London SE1 1UL, UK. Email: elizabeth.bradbury{at}kcl.ac.uk
Chondroitin sulfate proteoglycans (CSPGs) are inhibitory extracellular matrix molecules that are upregulated after CNS injury. Degradation of CSPGs using the enzyme chondroitinase ABC (ChABC) can promote functional recovery after spinal cord injury. However, the mechanisms underlying this recovery are not clear. Here we investigated the effects of ChABC treatment on promoting plasticity within the spinal cord. We found robust sprouting of both injured (corticospinal) and intact (serotonergic) descending projections as well as uninjured primary afferents after a cervical dorsal column injury and ChABC treatment. Sprouting fibers were observed in aberrant locations in degenerating white matter proximal to the injury in regions where CSPGs had been degraded. Corticospinal and serotonergic sprouting fibers were also observed in spinal gray matter at and below the level of the lesion, indicating increased innervation in the terminal regions of descending projections important for locomotion. Spinal-injured animals treated with a vehicle solution showed no significant sprouting. Interestingly, ChABC treatment in uninjured animals did not induce sprouting in any system. Thus, both denervation and CSPG degradation were required to promote sprouting within the spinal cord. We also examined potential detrimental effects of ChABC-induced plasticity. However, although primary afferent sprouting was observed after lumbar dorsal column lesions and ChABC treatment, there was no increased connectivity of nociceptive neurons or development of mechanical allodynia or thermal hyperalgesia. Thus, CSPG digestion promotes robust sprouting of spinal projections in degenerating and denervated areas of the spinal cord; compensatory sprouting of descending systems could be a key mechanism underlying functional recovery.
Key words: proteoglycan; plasticity; spinal cord; regeneration; denervation; repair
Received March 1, 2006; revised Aug. 29, 2006; accepted Sept. 5, 2006.
Correspondence should be addressed to Dr. Elizabeth J. Bradbury, Neurorestoration Group, Wolfson Centre for Age Related Diseases, King's College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London Bridge, London SE1 1UL, UK. Email: elizabeth.bradbury{at}kcl.ac.uk
This article has been cited by other articles:
S. A. Busch, K. P. Horn, D. J. Silver, and J. Silver
Overcoming Macrophage-Mediated Axonal Dieback Following CNS Injury
J. Neurosci., August 12, 2009; 29(32): 9967 - 9976.
[Abstract] [Full Text] [PDF]
J. W. Fawcett
Recovery from spinal cord injury: regeneration, plasticity and rehabilitation
Brain, June 1, 2009; 132(6): 1417 - 1418.
[Full Text] [PDF]
C. Darian-Smith
Synaptic Plasticity, Neurogenesis, and Functional Recovery after Spinal Cord Injury
Neuroscientist, April 1, 2009; 15(2): 149 - 165.
[Abstract] [PDF]
L. M. Carter, M. L. Starkey, S. F. Akrimi, M. Davies, S. B. McMahon, and E. J. Bradbury
The Yellow Fluorescent Protein (YFP-H) Mouse Reveals Neuroprotection as a Novel Mechanism Underlying Chondroitinase ABC-Mediated Repair after Spinal Cord Injury
J. Neurosci., December 24, 2008; 28(52): 14107 - 14120.
[Abstract] [Full Text] [PDF]
W. B. J. Cafferty, E. J. Bradbury, M. Lidierth, M. Jones, P. J. Duffy, S. Pezet, and S. B. McMahon
Chondroitinase ABC-Mediated Plasticity of Spinal Sensory Function
J. Neurosci., November 12, 2008; 28(46): 11998 - 12009.
[Abstract] [Full Text] [PDF]
Y. Sato, K. Nakanishi, M. Hayakawa, H. Kakizawa, A. Saito, Y. Kuroda, M. Ida, Y. Tokita, S. Aono, F. Matsui, et al.
Reduction of Brain Injury in Neonatal Hypoxic--Ischemic Rats by Intracerebroventricular Injection of Neural Stem/Progenitor Cells Together With Chondroitinase ABC
Reproductive Sciences, July 1, 2008; 15(6): 613 - 620.
[Abstract] [PDF]
X. Quaglia, A. T. Beggah, C. Seidenbecher, and A. D. Zurn
Delayed priming promotes CNS regeneration post-rhizotomy in Neurocan and Brevican-deficient mice
Brain, January 1, 2008; 131(1): 240 - 249.
[Abstract] [Full Text] [PDF]
Y.-S. Lee, C.-Y. Lin, V. J. Caiozzo, R. T. Robertson, J. Yu, and V. W. Lin
Repair of spinal cord transection and its effects on muscle mass and myosin heavy chain isoform phenotype
J Appl Physiol, November 1, 2007; 103(5): 1808 - 1814.
[Abstract] [Full Text] [PDF]
J. FitzGerald and J. Fawcett
Repair in the central nervous system
J Bone Joint Surg Br, November 1, 2007; 89-B(11): 1413 - 1420.
[Abstract] [Full Text] [PDF]
J. V. Priestley
Promoting anatomical plasticity and recovery of function after traumatic injury to the central or peripheral nervous system
Brain, April 1, 2007; 130(4): 895 - 897.
[Full Text] [PDF]
W. B. J. Cafferty, S.-H. Yang, P. J. Duffy, S. Li, and S. M. Strittmatter
Functional Axonal Regeneration through Astrocytic Scar Genetically Modified to Digest Chondroitin Sulfate Proteoglycans
J. Neurosci., February 28, 2007; 27(9): 2176 - 2185.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|