ArticleMolecular neurobiology2016
Myelin Lipids Inhibit Axon Regeneration Following Spinal Cord Injury: a Novel Perspective for Therapy.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Effects of sulfatide on peripheral nerves in metachromatic leukodystrophy.Annals of clinical and translational neurology · 2024Trial
- Elevated phagocytic capacity directs innate spinal cord repair.Cell reports · 2026Article
- Hmgcs1 regulates cholesterol synthesis and promotes nerve fiber repair after spinal cord injury.iScience · 2026Article
- Advanced Bioactive Polymers and Materials for Nerve Repair: Strategies and Mechanistic Insights.Journal of functional biomaterials · 2025Review
- Felodipine Promotes the Recovery of Mice With Spinal Cord Injury by Activating Macrolipophagy Through the AMPK-mTOR Pathway.Journal of cellular and molecular medicine · 2025Article
- Centripetal migration and prolonged retention of microglia promotes spinal cord injury repair.Journal of neuroinflammation · 2025Article
- hBcl2 overexpression in BMSCs enhances resistance to myelin debris-induced apoptosis and facilitates neuroprotection after spinal cord injury in rats.Scientific reports · 2024Article
- Targeting transcription factor pu.1 for improving neurologic outcomes after spinal cord injury.Frontiers in neuroscience · 2024Article
- Glycerophospholipid Analysis of Optic Nerve Regeneration Models Indicate Potential Membrane Order Changes Associated with the Lipidomic Shifts.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
- Macrophages Treated with VEGF and PDGF Exert Paracrine Effects on Olfactory Ensheathing Cell Function.Cells · 2022Article
- The Role of Tissue Geometry in Spinal Cord Regeneration.Medicina (Kaunas, Lithuania) · 2022Review
- Repeated Administration of 2-Hydroxypropyl-β-Cyclodextrin (HPβCD) Attenuates the Chronic Inflammatory Response to Experimental Stroke.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- One Raft to Guide Them All, and in Axon Regeneration Inhibit Them.International journal of molecular sciences · 2021Review
- Review
- Role of cholesterol and sphingolipids in brain development and neurological diseases.Lipids in health and disease · 2019Review
- Biomarkers in Spinal Cord Injury: from Prognosis to Treatment.Molecular neurobiology · 2018Review
- RhoA Inhibitor Treatment At Acute Phase of Spinal Cord Injury May Induce Neurite Outgrowth and Synaptogenesis.Molecular & cellular proteomics : MCP · 2017Article
- Macrophage Transcriptional Profile Identifies Lipid Catabolic Pathways That Can Be Therapeutically Targeted after Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Inhibitory Injury Signaling Represses Axon Regeneration After Dorsal Root Injury.Molecular neurobiology · 2016Article
- Sphingolipids in spinal cord injury.International journal of physiology, pathophysiology and pharmacology · 2016Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lack of axon regeneration following spinal cord injury has been mainly ascribed to the inhibitory environment of the injury site, i.e., to chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs). Here, we used shiverer (shi) mice to assess axon regeneration following spinal cord injury in the presence of MAIs and CSPG but in the absence of compact myelin. Although in vitro shi neurons displayed a similar intrinsic neurite outgrowth to wild-type neurons, in vivo, shi fibers had increased regenerative capacity, suggesting that the wild-type spinal cord contains additional inhibitors besides MAIs and CSPG. Our data show that besides myelin protein, myelin lipids are highly inhibitory for neurite outgrowth and suggest that this inhibitory effect is released in the shi spinal cord given its decreased lipid content. Specifically, we identified cholesterol and sphingomyelin as novel myelin-associated inhibitors that operate through a Rho-dependent mechanism and have inhibitory activity in multiple neuron types. We further demonstrated the inhibitory action of myelin lipids in vivo, by showing that delivery of 2-hydroxypropyl-β-cyclodextrin, a drug that reduces the levels of lipids specifically in the injury site, leads to increased axon regeneration of wild-type (WT) dorsal column axons following spinal cord injury. In summary, our work shows that myelin lipids are important modulators of axon regeneration that should be considered together with protein MAIs as critical targets in strategies aiming at improving axonal growth following injury.
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