ArticleNeuroscience2012
Prevention of posttraumatic axon sprouting by blocking collapsin response mediator protein 2-mediated neurite outgrowth and tubulin polymerization.
Article in Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 65 citations in OpenAlex.
- Review
- Lacosamide Is a Novel Drug That Improves AGTPBP1 Knockout-Mediated Impairment of Neuronal and Dopaminergic Function.Molecular neurobiology · 2025Article
- Inhibition of ERK1/2 or CRMP2 Disrupts Alcohol Memory Reconsolidation and Prevents Relapse in Rats.International journal of molecular sciences · 2024Article
- The therapeutic effects of lacosamide on epilepsy-associated comorbidities.Frontiers in neurology · 2023Review
- Neuropilin-2 Signaling Modulates Mossy Fiber Sprouting by Regulating Axon Collateral Formation Through CRMP2 in a Rat Model of Epilepsy.Molecular neurobiology · 2022Article
- CRMP2 is a therapeutic target that suppresses the aggressiveness of breast cancer cells by stabilizing RECK.Oncogene · 2020Article
- Nrp1 is Activated by Konjac Ceramide Binding-Induced Structural Rigidification of the a1a2 Domain.Cells · 2020Article
- Collapsin Response Mediator Proteins: Their Biological Functions and Pathophysiology in Neuronal Development and Regeneration.Frontiers in cellular neuroscience · 2020Article
- Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein-2 drive reinstatement of alcohol reward seeking.Addiction biology · 2019Article
- Modulation of CRMP2 via (Neuronal signaling · 2019Article
- Longitudinal Optogenetic Motor Mapping Revealed Structural and Functional Impairments and Enhanced Corticorubral Projection after Contusive Spinal Cord Injury in Mice.Journal of neurotrauma · 2019Article
- GSK3-CRMP2 signaling mediates axonal regeneration induced byCommunications biology · 2019Article
- CRMP2 Phosphorylation Drives Glioblastoma Cell Proliferation.Molecular neurobiology · 2018Article
- CRMP2 and voltage-gated ion channels: potential roles in neuropathic pain.Neuronal signaling · 2018Article
- Proteomic analysis of human epileptic neocortex predicts vascular and glial changes in epileptic regions.PloS one · 2018Article
- CRMPs Function in Neurons and Glial Cells: Potential Therapeutic Targets for Neurodegenerative Diseases and CNS Injury.Molecular neurobiology · 2017Review
- Boosting CNS axon regeneration by harnessing antagonistic effects of GSK3 activity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Neuroprotective Effect of Lacosamide on Hypoxic-Ischemic Brain Injury in Neonatal Rats.Journal of clinical neurology (Seoul, Korea) · 2017Article
- mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors.Molecular psychiatry · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Epileptogenesis following traumatic brain injury (TBI) is likely due to a combination of increased excitability, disinhibition, and increased excitatory connectivity via aberrant axon sprouting. Targeting these pathways could be beneficial in the prevention and treatment of posttraumatic epilepsy. Here, we tested this possibility using the novel anticonvulsant (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide [LCM]), which acts on both voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP2), an axonal growth/guidance protein. LCM inhibited CRMP2-mediated neurite outgrowth, an effect phenocopied by CRMP2 knockdown. Mutation of LCM-binding sites in CRMP2 reduced the neurite inhibitory effect of LCM by ∼8-fold. LCM also reduced CRMP2-mediated tubulin polymerization. Thus, LCM selectively impairs CRMP2-mediated microtubule polymerization, which underlies its neurite outgrowth and branching. To determine whether LCM inhibits axon sprouting in vivo, LCM was injected into rats subjected to partial cortical isolation, an animal model of posttraumatic epileptogenesis that exhibits axon sprouting in cortical pyramidal neurons. Two weeks following injury, excitatory synaptic connectivity of cortical layer V pyramidal neurons was mapped using patch clamp recordings and laser scanning photostimulation of caged glutamate. In comparison with injured control animals, there was a significant decrease in the map size of excitatory synaptic connectivity in LCM-treated rats, suggesting that LCM treatment prevented enhanced excitatory synaptic connectivity due to posttraumatic axon sprouting. These findings suggest, for the first time, that LCM's mode of action involves interactions with CRMP2 to inhibit posttraumatic axon sprouting.
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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.