ArticleExperimental neurology2018
Stimulation-dependent remodeling of the corticospinal tract requires reactivation of growth-promoting developmental signaling pathways.
Article in Experimental neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- Chronic activation of corticospinal tract neurons after pyramidotomy injury enhances neither behavioral recovery nor axonal sprouting.Experimental neurology · 2026Article
- Rejuvenation of corticospinal neurons enhances rehabilitation-associated corticospinal tract axon sprouting and functional recovery post photothrombotic ischemic stroke in mice.Genes & diseases · 2026Article
- 3D-Printing of Electroconductive MXene-Based Micro-Meshes in a Biomimetic Hyaluronic Acid-Based Scaffold Directs and Enhances Electrical Stimulation for Neural Repair Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transcranial Optogenetic Stimulation Promotes Corticospinal Tract Axon Regeneration to Repair Spinal Cord Injury by Activating the JAK2/STAT3 Pathway.Neurospine · 2025Article
- Combined biomaterial scaffold and neuromodulation strategy to promote tissue repair and corticospinal connectivity after spinal cord injury in a rodent model.Experimental neurology · 2024Article
- Molecular signaling predicts corticospinal axon growth state and muscle response plasticity induced by neuromodulation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Corticospinal-specific Shh overexpression in combination with rehabilitation promotes CST axonal sprouting and skilled motor functional recovery after ischemic stroke.Molecular neurobiology · 2024Article
- Osteopontin enhances the effect of treadmill training and promotes functional recovery after spinal cord injury.Molecular biomedicine · 2023Article
- Boosting corticospinal system synaptic plasticity to recover motor functions.Neural regeneration research · 2023Article
- Recent progress and challenges in the treatment of spinal cord injury.Protein & cell · 2023Review
- Suppression of Microglial ERO1a Alleviates Inflammation and Enhances the Efficacy of Rehabilitative Training After Ischemic Stroke.Molecular neurobiology · 2023Article
- Composite Fibrin/Carbon Microfiber Implants for Bridging Spinal Cord Injury: A Translational Approach in Pigs.International journal of molecular sciences · 2023Article
- Chronic muscle recordings reveal recovery of forelimb function in spinal injured female rats after cortical epidural stimulation combined with rehabilitation and chondroitinase ABC.Journal of neuroscience research · 2022Article
- Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury.Neural regeneration research · 2022Review
- Progression in translational research on spinal cord injury based on microenvironment imbalance.Bone research · 2022Review
- Effects of central nervous system electrical stimulation on non-neuronal cells.Frontiers in neuroscience · 2022Review
- Electroacupuncture Activates Neuroplasticity in the Motor Cortex and Corticospinal Tract via the mTOR Pathway in a Rat P-MCAO Model.BioMed research international · 2022Article
- Dual motor cortex and spinal cord neuromodulation improves rehabilitation efficacy and restores skilled locomotor function in a rat cervical contusion injury model.Experimental neurology · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The corticospinal tract (CST) can become damaged after spinal cord injury or stroke, resulting in weakness or paralysis. Repair of the damaged CST is limited because mature CST axons fail to regenerate, which is partly because the intrinsic axon growth capacity is downregulated in maturity. Whereas CST axons sprout after injury, this is insufficient to recover lost functions. Chronic motor cortex (MCX) electrical stimulation is a neuromodulatory strategy to promote CST axon sprouting, leading to functional recovery after CST lesion. Here we examine the molecular mechanisms of stimulation-dependent CST axonal sprouting and synapse formation. MCX stimulation rapidly upregulates mTOR and Jak/Stat signaling in the corticospinal system. Chronic stimulation, which leads to CST sprouting and increased CST presynaptic sites, further enhances mTOR and Jak/Stat activity. Importantly, chronic stimulation shifts the equilibrium of the mTOR repressor PTEN to the inactive phosphorylated form suggesting a molecular transition to an axon growth state. We blocked each signaling pathway selectively to determine potential differential contributions to axonal outgrowth and synapse formation. mTOR blockade prevented stimulation-dependent axon sprouting. Surprisingly, Jak/Stat blockade did not abrogate sprouting, but instead prevented the increase in CST presynaptic sites produced by chronic MCX stimulation. Chronic stimulation increased the number of spinal neurons expressing the neural activity marker cFos. Jak/Stat blockade prevented the increase in cFos-expressing neurons after chronic stimulation, confirming an important role for Jak/Stat signaling in activity-dependent CST synapse formation. MCX stimulation is a neuromodulatory repair strategy that reactivates distinct developmentally-regulated signaling pathways for axonal outgrowth and synapse formation.
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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.