ArticleStroke2012
Delayed administration of a small molecule tropomyosin-related kinase B ligand promotes recovery after hypoxic-ischemic stroke.
Article in Stroke, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 68 citations in OpenAlex.
- Trial
- Exercise mimetics: molecular mechanisms, biological and therapeutic effects.Molecular biomedicine · 2026Review
- Small-Molecule Trk Agonists: Where Do We Go from Here?Journal of medicinal chemistry · 2025Review
- A Small-Molecule TrkB/TrkC Ligand Promotes Neurogenesis and Behavioral Recovery Following Traumatic Brain Injury.Neurotrauma reports · 2025Article
- Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair?International journal of molecular sciences · 2023Review
- Investigation of 91 proteins implicated in neurobiological processes identifies multiple candidate plasma biomarkers of stroke outcome.Scientific reports · 2022Article
- Chronic partial TrkB activation reduces seizures and mortality in a mouse model of Dravet syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Restoration of motor learning in a mouse model of Rett syndrome following long-term treatment with a novel small-molecule activator of TrkB.Disease models & mechanisms · 2020Article
- Intrinsic Mechanisms Regulating Neuronal Migration in the Postnatal Brain.Frontiers in cellular neuroscience · 2020Review
- Post-stroke remodeling processes in animal models and humans.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- Loss of Adaptive Myelination Contributes to Methotrexate Chemotherapy-Related Cognitive Impairment.Neuron · 2019Article
- Innovative Therapy for Alzheimer's Disease-With Focus on Biodelivery of NGF.Frontiers in neuroscience · 2019Review
- TrkB Agonist LM22A-4 Increases Oligodendroglial Populations During Myelin Repair in the Corpus Callosum.Frontiers in molecular neuroscience · 2019Article
- A Small Molecule TrkB Neurotrophin Receptor Partial Agonist as Possible Treatment for Experimental Nonarteritic Anterior Ischemic Optic Neuropathy.Current eye research · 2018Article
- Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.Psychopharmacology · 2018Review
- Effect of Inhibition of DNA Methylation Combined with Task-Specific Training on Chronic Stroke Recovery.International journal of molecular sciences · 2018Article
- Targeting the intracellular signaling "STOP" and "GO" pathways for the treatment of alcohol use disorders.Psychopharmacology · 2018Review
- A small-molecule TrkB ligand restores hippocampal synaptic plasticity and object location memory in Rett syndrome mice.Disease models & mechanisms · 2017Article
- Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeStroke is the leading cause of long-term disability in the United States, yet no drugs are available that are proven to improve recovery. Brain-derived neurotrophic factor stimulates neurogenesis and plasticity, processes that are implicated in stroke recovery. It binds to both the tropomyosin-related kinase B and p75 neurotrophin receptors. However, brain-derived neurotrophic factor is not a feasible therapeutic agent, and no small molecule exists that can reproduce its binding to both receptors. We tested the hypothesis that a small molecule (LM22A-4) that selectively targets tropomyosin-related kinase B would promote neurogenesis and functional recovery after stroke.
methodsFour-month-old mice were trained on motor tasks before stroke. After stroke, functional test results were used to randomize mice into 2 equally, and severely, impaired groups. Beginning 3 days after stroke, mice received LM22A-4 or saline vehicle daily for 10 weeks.
resultsLM22A-4 treatment significantly improved limb swing speed and accelerated the return to normal gait accuracy after stroke. LM22A-4 treatment also doubled both the number of new mature neurons and immature neurons adjacent to the stroke. Drug-induced differences were not observed in angiogenesis, dendritic arborization, axonal sprouting, glial scar formation, or neuroinflammation.
conclusionsA small molecule agonist of tropomyosin-related kinase B improves functional recovery from stroke and increases neurogenesis when administered beginning 3 days after stroke. These findings provide proof-of-concept that targeting of tropomyosin-related kinase B alone is capable of promoting one or more mechanisms relevant to stroke recovery. LM22A-4 or its derivatives might therefore serve as "pro-recovery" therapeutic agents for stroke.
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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.