ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Large-scale chondroitin sulfate proteoglycan digestion with chondroitinase gene therapy leads to reduced pathology and modulates macrophage phenotype following spinal cord contusion injury.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.
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Who cites it
126 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- Stem Cell Strategies in Promoting Neuronal Regeneration after Spinal Cord Injury: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Noninvasive Focal Gene Delivery of Functional Neural Actuators to the Primate Spinal Cord using Focused Ultrasound.bioRxiv : the preprint server for biology · 2026Article
- Overcoming Barriers to Axonal Regeneration in Spinal Cord Injury: Mechanistic Insights and Therapeutic Frontiers.CNS neuroscience & therapeutics · 2026Review
- Widespread AAV-mediated CSPG digestion impairs functional recovery after cervical spinal cord injury.bioRxiv : the preprint server for biology · 2026Article
- Environmental Enrichment Preserves Retrosplenial Parvalbumin Density and Cognitive Function in Female 5xFAD Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Regional Molecular Diversity in Chronic Spinal Cord Injury.Cellular and molecular neurobiology · 2026Article
- Immune Activation Following Spinal Cord Injury: A Review Focused on Inflammatory Changes in the Spinal Cord.International journal of molecular sciences · 2025Review
- In vivo programming of adult pericytes aids axon regeneration by providing cellular bridges for SCI repair.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Molecular pathology of acute spinal cord injury in middle-aged mice.Journal of neuroinflammation · 2025Article
- Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Article
- Effects of chemogenetic virus injection and clozapine administration in spinal cord injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Chondroitinase ABC in spinal cord injury: advances in delivery strategies and therapeutic synergies.Frontiers in bioengineering and biotechnology · 2025Review
- Article
- Photobiomodulation Increases M2-Type Polarization of Macrophages by Inhibiting Versican Production After Spinal Cord Injury.Molecular neurobiology · 2024Article
- The potential of gene delivery for the treatment of traumatic brain injury.Journal of neuroinflammation · 2024Review
- Article
- Chondroitin Sulfate Proteoglycans Revisited: Its Mechanism of Generation and Action for Spinal Cord Injury.Aging and disease · 2024Review
- Recovery of Forearm and Fine Digit Function After Chronic Spinal Cord Injury by Simultaneous Blockade of Inhibitory Matrix Chondroitin Sulfate Proteoglycan Production and the Receptor PTPσ.Journal of neurotrauma · 2023Article
- Axonal growth inhibitors and their receptors in spinal cord injury: from biology to clinical translation.Neural regeneration research · 2023Review
- A Review of Treatment Methods Focusing on Human Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cell Transplantation for Chronic Spinal Cord Injury.Medicina (Kaunas, Lithuania) · 2023Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Chondroitin sulfate proteoglycans (CSPGs) inhibit repair following spinal cord injury. Here we use mammalian-compatible engineered chondroitinase ABC (ChABC) delivered via lentiviral vector (LV-ChABC) to explore the consequences of large-scale CSPG digestion for spinal cord repair. We demonstrate significantly reduced secondary injury pathology in adult rats following spinal contusion injury and LV-ChABC treatment, with reduced cavitation and enhanced preservation of spinal neurons and axons at 12 weeks postinjury, compared with control (LV-GFP)-treated animals. To understand these neuroprotective effects, we investigated early inflammatory changes following LV-ChABC treatment. Increased expression of the phagocytic macrophage marker CD68 at 3 d postinjury was followed by increased CD206 expression at 2 weeks, indicating that large-scale CSPG digestion can alter macrophage phenotype to favor alternatively activated M2 macrophages. Accordingly, ChABC treatment in vitro induced a significant increase in CD206 expression in unpolarized monocytes stimulated with conditioned medium from spinal-injured tissue explants. LV-ChABC also promoted the remodelling of specific CSPGs as well as enhanced vascularity, which was closely associated with CD206-positive macrophages. Neuroprotective effects of LV-ChABC corresponded with improved sensorimotor function, evident as early as 1 week postinjury, a time point when increased neuronal survival correlated with reduced apoptosis. Improved function was maintained into chronic injury stages, where improved axonal conduction and increased serotonergic innervation were also observed. Thus, we demonstrate that ChABC gene therapy can modulate secondary injury processes, with neuroprotective effects that lead to long-term improved functional outcome and reveal novel mechanistic evidence that modulation of macrophage phenotype may underlie these effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.