ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Enhanced subcortical spreading depression in familial hemiplegic migraine type 1 mutant mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 151 citations in OpenAlex.
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- Tsunamis hiding in plain sight: spreading depression in clinical neurology.Nature reviews. Neurology · 2026Review
- Is canonical SD a clinically relevant model of migraine? Argument con.The journal of headache and pain · 2025Review
- Sex differences in fixational eye movements following concussion.Journal of vision · 2025Article
- Spreading depolarization is followed by seizure-like activation of the hippocampus: potential mechanism of migraine-aura triggered seizures.The journal of headache and pain · 2025Article
- Persistent Na+ current couples spreading depolarization to seizures in Scn8a gain-of-function mice.Brain : a journal of neurology · 2025Article
- State-of-the-art preclinical techniques to study the impact of spreading depolarizations in awake rodents.The journal of headache and pain · 2025Review
- Article
- 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 is a dysfunction of neuronal potassium ion channels.Frontiers in neurology · 2025Review
- The complex molecular epileptogenesis landscape of glioblastoma.Cell reports. Medicine · 2024Article
- The effect of P2X7 antagonism on subcortical spread of optogenetically-triggered cortical spreading depression and neuroinflammation.The journal of headache and pain · 2024Article
- The Dawn and Advancement of the Knowledge of the Genetics of Migraine.Journal of clinical medicine · 2024Review
- Different vulnerability of fast and slow cortical oscillations to suppressive effect of spreading depolarization: state-dependent features potentially relevant to pathogenesis of migraine aura.The journal of headache and pain · 2024Article
- Chronic pregabalin treatment protects against spreading depolarization and alters hippocampal synaptic characteristics in a model of familial hemiplegic migraine-type 1.Molecular brain · 2023Article
- Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations.International journal of molecular sciences · 2023Review
- A hyperthermic seizure unleashes a surge of spreading depolarizations in Scn1a-deficient mice.JCI insight · 2023Article
- Levcromakalim provokes an acute rapid-onset migraine-like phenotype without inducing cortical spreading depolarization.The journal of headache and pain · 2023Article
- Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Familial hemiplegic migraine type 1, a monogenic migraine variant with aura, is linked to gain-of-function mutations in the CACNA1A gene encoding Ca(V)2.1 channels. The S218L mutation causes severe channel dysfunction, and paroxysmal migraine attacks can be accompanied by seizures, coma, and hemiplegia; patients expressing the R192Q mutation exhibit hemiplegia only. Familial hemiplegic migraine knock-in mice expressing the S218L or R192Q mutation are highly susceptible to cortical spreading depression, the electrophysiological surrogate for migraine aura, and develop severe and prolonged motor deficits after spreading depression. The S218L mutants also develop coma and seizures and sometimes die. To investigate underlying mechanisms for these symptoms, we used multielectrode electrophysiological recordings, diffusion-weighted magnetic resonance imaging, and c-fos immunohistochemistry to trace spreading depression propagation into subcortical structures. We showed that unlike the wild type, cortical spreading depression readily propagated into subcortical structures in both familial hemiplegic migraine type 1 mutants. Whereas the facilitated subcortical spread appeared limited to the striatum in R192Q, hippocampal and thalamic spread was detected in the S218L mutants with an allele-dosage effect. Both strains exhibited increased susceptibility to subcortical spreading depression and reverberating spreading depression waves. Altogether, these data show that spreading depression propagates between cortex, basal ganglia, diencephalon, and hippocampus in genetically susceptible brains, which could explain the prolonged hemiplegia, coma, and seizure phenotype in this variant of migraine with 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.