ArticleThe Journal of clinical investigation2009
Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 2 of them syntheses that pooled it.
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Who cites it
144 citing papers in PubMed, 2 syntheses or guidelines pooled it, 283 citations in OpenAlex.
- Sex-specific management of migraine a systematic review and consensus statement from the European Headache Federation (EHF).The journal of headache and pain · 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
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- The Estrogen-CGRP Axis in Migraine: Neuroimmune Mechanisms, Sex Differences, and Therapeutic Implications.Molecular neurobiology · 2026Review
- Tsunamis hiding in plain sight: spreading depression in clinical neurology.Nature reviews. Neurology · 2026Review
- Pediatric Migraine Aura Status and Cortical Laminar Necrosis: A Clinical Case and a Narrative Review.Revista de neurologia · 2026Review
- Spreading depolarization activates the cGAS-STING pathway and drives cranial nociception: therapeutic potential of STING modulation.The journal of headache and pain · 2026Article
- Is canonical SD a clinically relevant model of migraine? Argument pro.The journal of headache and pain · 2025Review
- Mechanisms underlying the increased susceptibility to initiation of cortical spreading depression in a genetic mouse model of migraine.The journal of headache and pain · 2025Article
- Contralesional hippocampal spreading depolarization promotes functional recovery after stroke.Nature communications · 2025Article
- Is migraine a common manifestation of CADASIL-Cons.The journal of headache and pain · 2025Article
- Is migraine a common manifestation of CADASIL? Arguments Pros.The journal of headache and pain · 2025Article
- The link between spreading depolarization and innate immunity in the central nervous system.The journal of headache and pain · 2025Review
- Mechanisms underlying CSD initiation implicated by genetic mouse models of migraine.The journal of headache and pain · 2025Review
- Migraine in men.The journal of headache and pain · 2025Review
- Sex differences in photophobic behaviors following cortical spreading depression in rats.Cephalalgia : an international journal of headache · 2025Article
- Article
- Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review.International journal of molecular sciences · 2024Review
- Increasing adult-born neurons protects mice from epilepsy.bioRxiv : the preprint server for biology · 2024Article
- A cross-sectional, multicenter survey of the prevalence and influencing factors for migraine in epilepsy.Epilepsia open · 2024Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have shown that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD frequency and propagation speed; enhanced corticostriatal propagation; and, similar to the human FHM1 phenotype, more severe and prolonged post-SD neurological deficits. The susceptibility to SD and neurological deficits is affected by allele dosage and is higher in S218L than R192Q mutants. Further, female S218L and R192Q mutant mice were more susceptible to SD and neurological deficits than males. This sex difference was abrogated by ovariectomy and senescence and was partially restored by estrogen replacement, implicating ovarian hormones in the observed sex differences in humans with FHM1. These findings demonstrate that genetic and hormonal factors modulate susceptibility to SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism for the phenotypic diversity of human migraine and aura.
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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.