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Chondroitinase ABC Digestion of the Perineuronal Net Promotes Functional Collateral Sprouting in the Cuneate Nucleus after Cervical Spinal Cord Injury
Open accessAbstract
Upregulation of extracellular chondroitin sulfate proteoglycans (CSPGs) after CNS injuries contributes to the impediment of functional recovery by restricting both axonal regeneration and synaptic plasticity. In the present study, the effect of degrading CSPGs with the application of the bacterial enzyme chondroitinase ABC (chABC) into the cuneate nucleus of rats partially denervated of forepaw dorsal column axons was examined. A dorsal column transection between the C6–C7 dorsal root entry zones was followed immediately by an ipsilateral brainstem injection of either chABC or a bacterial-derived control enzyme [penicillinase (P-ase)] and then subsequently (1 week later) followed with a second brainstem enzyme injection and cholera toxin B subunit (CTB) tracer injection into the ipsilateral forepaw digits and pads. After 1 additional week, the rats underwent electrophysiological receptive field mapping of the cuneate nucleus and/or anatomical evaluation. Examination of the brainstems of rats from each group revealed that CSPGs had been reduced after chABC treatment. Importantly, in the chABC-treated rats (but not in the P-ase controls), a significantly greater area of the cuneate nucleus was occupied by physiologically active CTB traced forepaw afferents that had been spared by the initial cord lesion. These results demonstrate, for the first time, a functional change directly linked to anatomical evidence of sprouting by spinal cord afferents after chABC treatment.
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“but also contributed to expanded receptive fields of uninjured primary afferents (Bradbury et al., 2002; Massey et al., 2006).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Massey et al., 2006
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“This not only resulted in an increase in terminals from initially injured afferents”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Massey et al., 2006
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“CSPG degradation via application of chABC promoted regeneration of dorsal column axons after injury.”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Massey et al., 2006
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Metadata
- Authors
- Massey, J. M., Hubscher, C. H., Wagoner, M. R., Decker, J. A., Amps, J., Silver, J., & Onifer, S. M.
- Affiliations
- University of Louisville (US)
- University of Kentucky (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-04-19
- Volume
- 26
- Issue
- 16
- Pages
- 4406-4414
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6673998
- OpenAlex
- W1966007526
- Cited by
- 320
- References
- 56
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 11 · 2021: 9 · 2020: 17 · 2019: 14 · 2018: 21 · 2017: 13 · 2016: 16 · 2015: 16 · 2014: 29 · 2013: 19 · 2012: 27
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9874764)
- Yale University
- University of Louisville
- National Institutes of Health
- U.S. Public Health Service (25713)
- National Institute of Neurological Disorders and Stroke (NS-40411, R01NS040411)
- National Center for Research Resources (RR-15576, P20RR015576)
- 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
- chondroitinase ABC, perineuronal nets, chondroitin sulfate proteoglycans, cervical spinal cord injury, cuneate nucleus, collateral sprouting, axon regeneration, penicillinase, receptive field mapping
- MeSH terms
- Afferent Pathways, Animals, Cervical Vertebrae, Male, Nerve Net, Nerve Regeneration, Neuronal Plasticity, Peripheral Nerves, Pilot Projects, Chondroitin Sulfate Proteoglycans, Spinal Cord Injuries, Rats, Sprague-Dawley, Chondroitin ABC Lyase, Rats
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