The DOI matches its Crossref record; 112 of the 114 references it cites were found in a registry or an index.
Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3.
Open accessAbstract
Increased chondroitin sulfate proteoglycan (CSPG) expression in the vicinity of a spinal cord injury (SCI) is a primary participant in axonal regeneration failure. However, the presence of similar increases of CSPG expression in denervated synaptic targets well away from the primary lesion and the subsequent impact on regenerating axons attempting to approach deafferented neurons have not been studied. Constitutively expressed CSPGs within the extracellular matrix and perineuronal nets of the adult rat dorsal column nuclei (DCN) were characterized using real-time PCR, Western blot analysis and immunohistochemistry. We show for the first time that by 2 days and through 3 weeks following SCI, the levels of NG2, neurocan and brevican associated with reactive glia throughout the DCN were dramatically increased throughout the DCN despite being well beyond areas of trauma-induced blood brain barrier breakdown. Importantly, regenerating axons from adult sensory neurons microtransplanted 2 weeks following SCI between the injury site and the DCN were able to regenerate rapidly within white matter (as shown previously by Davies et al. [Davies, S.J., Goucher, D.R., Doller, C., Silver, J., 1999. Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J. Neurosci. 19, 5810-5822]) but were unable to enter the denervated DCN. Application of chondroitinase ABC or neurotrophin-3-expressing lentivirus in the DCN partially overcame this inhibition. When the treatments were combined, entrance by regenerating axons into the DCN was significantly augmented. These results demonstrate both an additional challenge and potential treatment strategy for successful functional pathway reconstruction after SCI.
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“In rat spinal cord injury models, increased concentrations of CSPGs and PNN expression were found at injury sites and surrounding secondary dorsal column relay neurons (Massey et al., 2008).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Massey et al., 2008
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Citations
Cites
Regeneration beyond the glial scar
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Self-citationTrk Receptors: Roles in Neuronal Signal Transduction
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“NT-3 through activation of axonal Trk receptors and subsequent intracellular signaling (for review see Huang and Reichardt, 2003) stimulate regeneration despite the presence of CSPGs and other inhibitory molecules (Oudega and Hagg, 1996; Bradbury et al., 1999; Oudega and Hagg, 1999; Lu et al.,…”
BackgroundChondroitinase ABC promotes functional recovery after spinal cord injury
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Self-citationMassive Cortical Reorganization After Sensory Deafferentation in Adult Macaques
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Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms
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Self-citationThe Biology of Regeneration Failure and Success After Spinal Cord Injury
Tran, A. P., Warren, P. M., & Silver, J. (2018) · Physiological Reviews · doi:10.1152/physrev.00017.2017 · Cited by 903
Self-citationAnimals lacking link protein have attenuated perineuronal nets and persistent plasticity
Carulli, D., Pizzorusso, T., Kwok, J. C. F., Putignano, E., Poli, A., Forostyak, S., Andrews, M. R., Deepa, S. S., Glant, T. T., & Fawcett, J. W. (2010) · Brain · doi:10.1093/brain/awq145 · Cited by 495
Extracellular matrix and perineuronal nets in CNS repair
Kwok, J. C. F., Dick, G., Wang, D., & Fawcett, J. W. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20974 · Cited by 395
Metadata
- Authors
- Massey, J. M., Amps, J., Viapiano, M. S., Matthews, R. T., Wagoner, M. R., Whitaker, C. M., Alilain, W., Yonkof, A. L., Khalyfa, A., Cooper, N. G. F., Silver, J., & Onifer, S. M.
- Affiliations
- University of Louisville (US)
- Case Western Reserve University (US)
- Yale University (US)
- Corresponding author
- Onifer, Stephen M.
- ORCID
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 209
- Issue
- 2
- Pages
- 426-445
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC2270474
- OpenAlex
- W1998297893
- Cited by
- 185
- References
- 114
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 8 · 2018: 9 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 15 · 2013: 15 · 2012: 15
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (NS25713, NS40411, RR15576, RR16481)
- Office of Experimental Program to Stimulate Competitive Research (EPS-9874764)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- chondroitin sulfate proteoglycans, spinal cord injury, axon regeneration, denervation, dorsal column nuclei, chondroitinase ABC, neurotrophin-3, NG2, neurocan, brevican, perineuronal nets, sensory neurons, white matter, reactive glia
- MeSH terms
- Chondroitin Sulfate Proteoglycan 4, Animals, Antigens, Brain Stem, Cholera Toxin, Disease Models, Animal, Extracellular Matrix, Ganglia, Spinal, Gene Expression Regulation, Genetic Vectors, Male, Nerve Tissue Proteins, Chondroitin Sulfate Proteoglycans, Proteoglycans, Random Allocation, Spinal Cord Injuries, Time Factors, Genetic Therapy, Rats, Sprague-Dawley, Cell Transplantation, Chondroitin ABC Lyase, Neurotrophin 3, Rats
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