ArticlePLoS genetics2011
Increased susceptibility to cortical spreading depression in the mouse model of familial hemiplegic migraine type 2.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 219 citations in OpenAlex.
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- Whole brain fluorescence imaging iniScience · 2026Article
- Spreading depolarization: A wave that precedes and drives cerebral ischemic cell death-Target for neuroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Dissociated neurovascular dynamics in ATP1A2-related familial hemiplegic migraine mimicking acute ischemic stroke.BMC neurology · 2026Article
- Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- 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
- State-of-the-art preclinical techniques to study the impact of spreading depolarizations in awake rodents.The journal of headache and pain · 2025Review
- Investigate channel rectifications and neural dynamics by an electrodiffusive Gauss-Nernst-Planck approach.PLoS computational biology · 2025Article
- All Three Supersystems-Nervous, Vascular, and Immune-Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage.Translational stroke research · 2025Review
- Mechanisms underlying CSD initiation implicated by genetic mouse models of migraine.The journal of headache and pain · 2025Review
- Migraine with brainstem aura with abnormal EEG discharges easily misdiagnosed as epilepsy: a case series study.Therapeutic advances in neurological disorders · 2025Article
- Epilepsy and migraine: a diagnostic and therapeutic challenge.Frontiers in pharmacology · 2025Review
- Interplay between cannabinoids and the neuroimmune system in migraine.The journal of headache and pain · 2024Review
- Higher sodium in older individuals or after stroke/reperfusion, but not in migraine or Alzheimer's disease - a study in different preclinical models.Scientific reports · 2024Article
- From spreading depolarization to blood-brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy.Nature reviews. Neurology · 2024Review
- A comprehensive exploration of astrocytes in migraine: a bibliometric and visual analysis.European journal of medical research · 2024Review
- The Dawn and Advancement of the Knowledge of the Genetics of Migraine.Journal of clinical medicine · 2024Review
- Spreading depolarizations pose critical energy challenges in acute brain injury.Journal of neurochemistry · 2024Review
- Review
- Models of Trigeminal Activation: Is There an Animal Model of Migraine?Brain sciences · 2024Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant form of migraine with aura that is caused by mutations of the α2-subunit of the Na,K-ATPase, an isoform almost exclusively expressed in astrocytes in the adult brain. We generated the first FHM2 knock-in mouse model carrying the human W887R mutation in the Atp1a2 orthologous gene. Homozygous Atp1a2(R887/R887) mutants died just after birth, while heterozygous Atp1a2(+/R887) mice showed no apparent clinical phenotype. The mutant α2 Na,K-ATPase protein was barely detectable in the brain of homozygous mutants and strongly reduced in the brain of heterozygous mutants, likely as a consequence of endoplasmic reticulum retention and subsequent proteasomal degradation, as we demonstrate in transfected cells. In vivo analysis of cortical spreading depression (CSD), the phenomenon underlying migraine aura, revealed a decreased induction threshold and an increased velocity of propagation in the heterozygous FHM2 mouse. Since several lines of evidence involve a specific role of the glial α2 Na,K pump in active reuptake of glutamate from the synaptic cleft, we hypothesize that CSD facilitation in the FHM2 mouse model is sustained by inefficient glutamate clearance by astrocytes and consequent increased cortical excitatory neurotransmission. The demonstration that FHM2 and FHM1 mutations share the ability to facilitate induction and propagation of CSD in mouse models further support the role of CSD as a key migraine trigger.
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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.