ArticleEMBO molecular medicine2016
Defective glutamate and K+ clearance by cortical astrocytes in familial hemiplegic migraine type 2.
Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis 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.
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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
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- A systematic literature review on the role of glial cells in the pathomechanisms of migraine.Frontiers in molecular neuroscience · 2023Pooled it
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- From bench to bedside: relevant animal models across the migraine attack phases.The journal of headache and pain · 2026Review
- Dissociated neurovascular dynamics in ATP1A2-related familial hemiplegic migraine mimicking acute ischemic stroke.BMC neurology · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Targeting glial-orchestrated neuroinflammation in migraine pathophysiology.The journal of headache and pain · 2026Review
- Neuroinflammatory and Redox Responses in a Rat Model of NTG-Induced Migraine.International journal of molecular sciences · 2025Article
- 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
- Article
- Reactive Astrocytes with Reduced Function of Glutamate Transporters in theACS chemical neuroscience · 2025Article
- Potassium homeostasis during disease progression of Alzheimer's disease.The Journal of physiology · 2025Article
- The mysterious link between migraine aura and migraine headache.PLoS biology · 2025Article
- GABAergic neurons can facilitate the propagation of cortical spreading depolarization: experiments in mouse neocortical slices and a novel neural field computational model.PLoS computational biology · 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
- The lethal homozygous variant in the ATP1A2 gene is associated with FARIMPD syndrome phenotypes in newborns.Neurogenetics · 2024Article
- Article
- Glial activation in pain and emotional processing regions in the nitroglycerin mouse model of chronic migraine.Headache · 2024Article
- Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.Aging and disease · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 2: FHM2) is caused by loss-of-function mutations in α2 Na(+),K(+) ATPase (α2 NKA), an isoform almost exclusively expressed in astrocytes in adult brain. Cortical spreading depression (CSD), the phenomenon that underlies migraine aura and activates migraine headache mechanisms, is facilitated in heterozygous FHM2-knockin mice with reduced expression of α2 NKA The mechanisms underlying an increased susceptibility to CSD in FHM2 are unknown. Here, we show reduced rates of glutamate and K(+) clearance by cortical astrocytes during neuronal activity and reduced density of GLT-1a glutamate transporters in cortical perisynaptic astrocytic processes in heterozygous FHM2-knockin mice, demonstrating key physiological roles of α2 NKA and supporting tight coupling with GLT-1a. Using ceftriaxone treatment of FHM2 mutants and partial inhibition of glutamate transporters in wild-type mice, we obtain evidence that defective glutamate clearance can account for most of the facilitation of CSD initiation in FHM2-knockin mice, pointing to excessive glutamatergic transmission as a key mechanism underlying the vulnerability to CSD ignition in 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.