Delayed priming promotes CNS regeneration post-rhizotomy in Neurocan and Brevican-deficient mice
Open accessAbstract
A wealth of literature has provided evidence that reactive tissue at the site of CNS injury is rich in chondroitin sulfate proteoglycans which may contribute to the non-permissive nature of the CNS. We have recently demonstrated using a murine model of human brachial plexus injury that the chondroitin sulfate proteoglycans Neurocan and Brevican are differentially expressed by two subsets of astrocytes in the spinal cord dorsal root entry zone (DREZ) following dorsal root lesion (Beggah et al., Neuroscience 133: 749-762, 2005). However, direct evidence for a growth-inhibitory role of these proteoglycans in vivo is still lacking. We therefore performed dorsal root lesion (rhizotomy) in mice deficient in both Neurocan and Brevican. Rhizotomy in these animals resulted in no significant increase in the number of sensory fibres regenerating through the DREZ compared to genetically matched controls. Likewise, a conditioning peripheral nerve lesion prior to rhizotomy, which increases the intrinsic growth capacity of sensory neurons, enhanced growth to the same extent in transgenic and control mice, indicating that absence of these proteoglycans alone is not sufficient to further promote entry into the spinal cord. In contrast, when priming of the median nerve was performed at a clinically relevant time, i.e. 7 weeks post-rhizotomy, the growth of a subpopulation of sensory axons across the DREZ was facilitated in Neurocan/Brevican-deficient, but not in control animals. This demonstrates for the first time that (i) Neurocan and/or Brevican contribute to the non-permissive environment of the DREZ several weeks after lesion and that (ii) delayed stimulation of the growth program of sensory neurons can facilitate regeneration across the DREZ provided its growth-inhibitory properties are attenuated. Post-injury enhancement of the intrinsic growth capacity of sensory neurons combined with removal of inhibitory chondroitin sulfate proteoglycans may therefore help to restore sensory function and thus attenuate the chronic pain resulting from human brachial plexus injury.
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BCAN−/− mice are brevican knockout.
“brevican knockout mice (BCAN−/−) mice”
From Aggrecan, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress (2014) · cites this paper as [55]
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- Authors
- Quaglia, X., Beggah, A. T., Seidenbecher, C., & Zurn, A. D.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- ORCID
- Seidenbecher, C.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-12-03
- Volume
- 131
- Issue
- 1
- Pages
- 240-249
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2100061187
- Cited by
- 24
- References
- 38
- Citations by year
- 2021: 3 · 2020: 3 · 2016: 1 · 2015: 1 · 2014: 3 · 2012: 2
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Keywords
- central nervous system regeneration, rhizotomy, neurocan, brevican, chondroitin sulfate proteoglycans, dorsal root entry zone, sensory axon regeneration, brachial plexus injury, sensory neurons, growth inhibition, chronic pain, astrocytes
- MeSH terms
- Animals, Brachial Plexus, Disease Models, Animal, Median Nerve, Mice, Inbred C57BL, Nerve Fibers, Nerve Regeneration, Nerve Tissue Proteins, Neurons, Afferent, Chondroitin Sulfate Proteoglycans, Proteoglycans, Regional Blood Flow, Spinal Nerve Roots, Mice, Knockout, Rhizotomy, Lectins, C-Type, Mice, Neurocan, Brevican
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