ArticleJournal of neurochemistry2012
Insulin-like growth factor-1 lowers spreading depression susceptibility and reduces oxidative stress.
Article in Journal of neurochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Compartment-specific redox modulation in migraine with aura: a systematic review of context-dependent mechanisms.Journal of oral & facial pain and headache · 2026Pooled it
- Systematic review of the pharmacological agents that have been tested against spreading depolarizations.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Pooled it
- Weather, air pollution, and migraine: A case-time series analysis examining environmental exposures and transient health outcomes recorded via smartphone application.Environmental epidemiology (Philadelphia, Pa.) · 2026Article
- Oxidative Stress in Migraine-Effect or Cause?Genes · 2026Review
- Is canonical SD a clinically relevant model of migraine? Argument pro.The journal of headache and pain · 2025Review
- Quantitative, real-time imaging of spreading depolarization-associated neuronal ROS production.Frontiers in cellular neuroscience · 2024Article
- Cortical Spreading Depolarization and Delayed Cerebral Ischemia; Rethinking Secondary Neurological Injury in Subarachnoid Hemorrhage.International journal of molecular sciences · 2023Review
- Circulating Insulin-Like Growth Factor 1 Levels and Migraine Risk: A Mendelian Randomization Study.Neurology and therapy · 2022Article
- Microglia Modulate Cortical Spreading Depolarizations After Ischemic Stroke: A Narrative Review.Neurocritical care · 2022Review
- Parenchymal neuroinflammatory signaling and dural neurogenic inflammation in migraine.The journal of headache and pain · 2021Review
- Insulin-like growth factor-1 inhibits nitroglycerin-induced trigeminal activation of oxidative stress, calcitonin gene-related peptide and c-Fos expression.Neuroscience letters · 2021Article
- SECISBP2 is a novel prognostic predictor that regulates selenoproteins in diffuse large B-cell lymphoma.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Article
- Membrane Depolarization and Apoptosis-Like Cell Death in an Alkaline Environment in the Rice PathogenFrontiers in microbiology · 2021Article
- Environmental Enrichment and Its Benefits for Migraine: Dendritic Cell Extracellular Vesicles as an Effective Mimetic.Journal of cellular immunology · 2021Article
- Mitochondrial dysfunction and role in spreading depolarization and seizure.Journal of computational neuroscience · 2019Article
- Astrocytic Insulin-Like Growth Factor-1 Protects Neurons Against Excitotoxicity.Frontiers in cellular neuroscience · 2019Article
- IFNγ-Stimulated Dendritic Cell Exosomes for Treatment of Migraine Modeled Using Spreading Depression.Frontiers in neuroscience · 2019Article
- Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Intranasally administered IGF-1 inhibits spreading depression in vivo.Brain research · 2017Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Spreading depression (SD), the likely cause of migraine aura and perhaps migraine, is triggered by widespread and unfettered neuronal hyperexcitability. Migraine and the initiating hyperexcitability of seizure, which involve oxidative stress (OS), are likely interrelated. Environmental enrichment (EE) decreases seizure and can reduce migraine. EE's well-characterized neuroprotective effect involves insulin-like growth factor-1 (IGF-1). Accordingly, we asked if IGF-1 could mitigate the hyperexcitability that initiates SD using rat hippocampal slice cultures. We demonstrate that IGF-1 significantly decreased SD susceptibility and related OS. We mimicked OS of SD and observed that IGF-1 abolished hyperexcitability from OS. Application of an antioxidant significantly decreased SD susceptibility and co-administration of an antioxidant with IGF-1 produced no additive effect, whereas an oxidizer significantly increased SD, and this effect was abrogated by IGF-1. Moreover, IGF-1 significantly decreased baseline OS, despite seemingly paradoxically increasing CA3 bursting. These results suggest that IGF-1 increased endogenous antioxidants to levels sufficient to buffer against the OS of SD. Insulin similarly mitigated SD susceptibility, but required a far greater dose. Since brain IGF-1 increases with EE, and, like insulin, independently functions as an EE mimetic, we suggest that EE mimetics are a novel source of therapeutics for SD, and by extension, migraine.
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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.