ArticleThe Journal of clinical investigation2021
Initiation of migraine-related cortical spreading depolarization by hyperactivity of GABAergic neurons and NaV1.1 channels.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Elicited Repetitive Daily Blindness Associated With Gain-of-FunctionNeurology. Genetics · 2026Article
- Voltage-gated sodium channels in the nervous system: Molecular physiology to therapeutic interventions.Neural regeneration research · 2026Article
- Therapeutic Overlap Between Bipolar Disorder and Migraine: A Systematic Review of Pharmacological Trials.Pharmaceuticals (Basel, Switzerland) · 2026Review
- BETMB: A Dual-Target Compound for Synergistic Suppression of Neuronal Hyperexcitability in Refractory Epilepsy via Concurrent Modulation of Nav Channels and GABACNS neuroscience & therapeutics · 2026Article
- Peripheral Immune and Metabolic Dysregulation in Migraine, Ménière's Disease, and Vestibular Migraine: A Single-Cell Atlas Study.Human mutation · 2026Article
- Persistent Na+ current couples spreading depolarization to seizures in Scn8a gain-of-function mice.Brain : a journal of neurology · 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
- Dynamics and conditions for inhibitory synaptic current to induce bursting and spreading depolarization in pyramidal neurons.Scientific reports · 2025Article
- Article
- Article
- Pharmacological inhibition of all known major inward cationic currents does not block the induction of spreading depolarizations.Frontiers in cellular neuroscience · 2025Article
- Voltage-gated sodium channels in genetic epilepsy: up and down of excitability.Journal of neurochemistry · 2024Review
- Voltage-gated sodium channels in genetic epilepsy: up and down of excitability.Journal of neurochemistry · 2024Review
- Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review.International journal of molecular sciences · 2024Review
- Conotoxins Targeting Voltage-Gated Sodium Ion Channels.Pharmacological reviews · 2024Review
- Brainstem depolarization-induced lethal apnea associated with gain-of-functionProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Brainstem depolarization-induced lethal apnea associated with gain-of-functionProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations.International journal of molecular sciences · 2023Review
- Mechanisms of initiation of cortical spreading depression.The journal of headache and pain · 2023Article
- Involvement of GABAergic Interneuron Subtypes in 4-Aminopyridine-Induced Seizure-Like Events in Mouse Entorhinal CortexThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spreading depolarizations (SDs) are involved in migraine, epilepsy, stroke, traumatic brain injury, and subarachnoid hemorrhage. However, the cellular origin and specific differential mechanisms are not clear. Increased glutamatergic activity is thought to be the key factor for generating cortical spreading depression (CSD), a pathological mechanism of migraine. Here, we show that acute pharmacological activation of NaV1.1 (the main Na+ channel of interneurons) or optogenetic-induced hyperactivity of GABAergic interneurons is sufficient to ignite CSD in the neocortex by spiking-generated extracellular K+ build-up. Neither GABAergic nor glutamatergic synaptic transmission were required for CSD initiation. CSD was not generated in other brain areas, suggesting that this is a neocortex-specific mechanism of CSD initiation. Gain-of-function mutations of NaV1.1 (SCN1A) cause familial hemiplegic migraine type-3 (FHM3), a subtype of migraine with aura, of which CSD is the neurophysiological correlate. Our results provide the mechanism linking NaV1.1 gain of function to CSD generation in FHM3. Thus, we reveal the key role of hyperactivity of GABAergic interneurons in a mechanism of CSD initiation, which is relevant as a pathological mechanism of Nav1.1 FHM3 mutations, and possibly also for other types of migraine and diseases in which SDs are involved.
Indexed as
Identifiers
What OpenQuestion holds
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.