ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Expression of an Activated Integrin Promotes Long-Distance Sensory Axon Regeneration in the Spinal Cord.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
- Chondroitin Sulfate Proteoglycans in CNS Development and Pathophysiology.Journal of neuroscience research · 2026Review
- AxoMetric platform facilitates rapid and unbiased automated quantification of axon regeneration in tissue sections.Cell reports methods · 2026Article
- From Regeneration Failure to Functional Restoration: Unlocking the Neuronal-Intrinsic Regenerative Capacity as a Therapeutic Frontier for Optic Neuropathy and Glaucoma.CNS neuroscience & therapeutics · 2026Review
- Mechanisms and Applications of Conductive Biomaterials in Spinal Cord Injury Repair.Biomaterials research · 2026Review
- Activated alpha 9 integrin expression enables sensory pathway reconstruction after spinal cord injury.Acta neuropathologica communications · 2025Article
- Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement.Nature communications · 2025Article
- (Re)building the nervous system: A review of neuron-glia interactions from development to disease.Journal of neurochemistry · 2025Review
- Combined strategy of α 9-integrin transduction and AEIDGIEL peptide-functionalized fibrin gel biomaterials to promote mature DRG neurite growth.Frontiers in cellular neuroscience · 2025Article
- Neuronal maturation and axon regeneration: unfixing circuitry to enable repair.Nature reviews. Neuroscience · 2024Review
- Review
- Integrin-Driven Axon Regeneration in the Spinal Cord Activates a Distinctive CNS Regeneration Program.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets.Biomedicines · 2022Review
- Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system.Nature communications · 2022Article
- Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling.Neural regeneration research · 2022Review
- Synaptic or Non-synaptic? Different Intercellular Interactions with Retinal Ganglion Cells in Optic Nerve Regeneration.Molecular neurobiology · 2022Review
- Extracellular Matrix in Neural Plasticity and Regeneration.Cellular and molecular neurobiology · 2022Review
- New insights into glial scar formation after spinal cord injury.Cell and tissue research · 2022Review
- Sex differences in affective states and association with voluntary ethanol intake in Sprague-Dawley rats.Psychopharmacology · 2022Article
- Integrin Signaling in the Central Nervous System in Animals and Human Brain Diseases.International journal of molecular sciences · 2022Review
- Long-Term Cultures of Spinal Cord Interneurons.Frontiers in cellular neuroscience · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
unlabelledAfter CNS injury, axon regeneration is blocked by an inhibitory environment consisting of the highly upregulated tenascin-C and chondroitin sulfate proteoglycans (CSPGs). Tenascin-C promotes growth of axons if they express a tenascin-binding integrin, particularly α9β1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a β1-binding integrin activator, kindlin-1. We examined the synergistic effect of α9 integrin and kindlin-1 on sensory axon regeneration in adult rat spinal cord after dorsal root crush and adeno-associated virus transgene expression in dorsal root ganglia. After 12 weeks, axons from C6-C7 dorsal root ganglia regenerated through the tenascin-C-rich dorsal root entry zone into the dorsal column up to C1 level and above (>25 mm axon length) through a normal pathway. Animals also showed anatomical and electrophysiological evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, thermal pain, and ladder-walking tasks. Expression of α9 integrin or kindlin-1 alone promoted much less regeneration and recovery. SIGNIFICANCE STATEMENT: The study demonstrates that long-distance sensory axon regeneration over a normal pathway and with sensory and sensory-motor recovery can be achieved. This was achieved by expressing an integrin that recognizes tenascin-C, one of the components of glial scar tissue, and an integrin activator. This enabled extensive long-distance (>25 mm) regeneration of both myelinated and unmyelinated sensory axons with topographically correct connections in the spinal cord. The extent of growth and recovery we have seen would probably be clinically significant. Restoration of sensation to hands, perineum, and genitalia would be a significant improvement for a spinal cord-injured patient.
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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.