ArticleThe journal of headache and pain2025
Spreading depolarization is followed by seizure-like activation of the hippocampus: potential mechanism of migraine-aura triggered seizures.
Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Local targeted suppression of neocortical spreading depolarization amplitude by viral expression of KCa3.1 channels.Gene therapy · 2026Article
- Multifocal Initiation of Spreading Depolarization by Generalized Tonic-Clonic Seizures.International journal of molecular sciences · 2026Article
- Dual role of spreading depolarization in an epileptic focus.Epilepsia · 2026Article
- Heightened Sensitivity of the Hyperexcitable Occipital Cortex to Spreading Depression: Evidence for State-Dependent Mechanisms of Migraine Aura.Neurology international · 2026Article
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3 authors.
Funding
Abstract
backgroundPropagation of spreading depolarization (SD), a wave of transient cellular depolarization, over the cerebral cortex drives migraine aura symptoms. Growing evidence suggests that hippocampus, brain region involved in regulation of mood and cognition, also contributes to pathogenesis of migraine. Hippocampus has highly inhomogeneous functional anatomy with strong dorsoventral difference in functional and network properties. We hypothesized that cerebral dysfunction induced by SD also varies within the hippocampus and studied characteristics and effects of SD in the dorsal and ventral hippocampus of awake animals. Given high susceptibility of the hippocampus to seizures, we focused on excitatory effects of SD.
methodsUnilateral SD was induced by a pinprick of the dorsal hippocampus in freely behaving rats. In electrophysiological experiments, local field potentials were recorded bilaterally in different sites along the dorsoventral axis of the hippocampus; propagation patterns, electrographic manifestations and excitatory effects of SD were evaluated. In separate experiments, effect of hippocampal SD on behavior was assessed.
resultsSD waveforms varied depending on local cytoarchitecture of hippocampal zones (CA, dentate gyrus and fiber-rich areas), irrespectively of their dorsoventral level. In the dentate gyrus, unusual double-wave SDs were recorded. Reaching ventral hippocampus, unilateral SD triggered a bilateral seizure-like discharge recruited both ipsilateral (affected by SD) and contralateral (unaffected by SD) sides. The post-SD activation of the ventral hippocampus had striking behavioral manifestation - a bout of wet dog shakes.
conclusionsThis is the first experimental evidence that SD can trigger seizure-like activity in particular regions of awake non-epileptic brain. We suggest that the phenomenon may be relevant to mechanisms of migraine-aura triggered seizures (migralepsy).
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