Rodent and human seizures demonstrate a dynamic interplay with spreading depolarizations
Seizure termination has been linked to spreading depolarizations (SDs) in experimental models of epilepsy, and SDs have been suggested to protect against seizures. However, the precise mechanisms of seizure-associated SDs remain unclear. Additionally, the co-occurrence of SDs with human seizures rem...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125001536 |
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| Summary: | Seizure termination has been linked to spreading depolarizations (SDs) in experimental models of epilepsy, and SDs have been suggested to protect against seizures. However, the precise mechanisms of seizure-associated SDs remain unclear. Additionally, the co-occurrence of SDs with human seizures remains debated.In this study, we found that SDs are a prominent feature following ictal events in both human clinical recordings and in a rodent model of ictogenesis. Approximately one-third of rodent seizure-like events (SLEs) associated with SDs, while all human seizures analyzed associated with propagating infraslow shifts, indicative of SDs. In rodents, SDs clustered towards the end of ictal events, resulting in significantly shorter SLEs and delayed onset of subsequent SLEs. Interestingly, SLEs with SDs displayed significantly more low gamma activity during ictal events than SLEs that did not end in SDs. Furthermore, we found no significant correlation between [K+]o levels and the likelihood of SLEs ending in SDs, questioning the role of [K+]o in SD induction during seizures. Interestingly, the human data demonstrate clear SD propagation during seizures and show that SDs appear and propagate in multiple brain regions simultaneously with ictal events.Collectively, these results indicate that SDs are a hallmark of ictal activity associated with seizure termination. Furthermore, these findings provide unique insight into the neuronal dynamics that promote SD induction by showing that increased low gamma activity during SLEs is more predictive of SD induction than [K+]o levels. Taken together, these findings provide rationale for further exploration of SDs to prematurely terminate life-threatening seizures. |
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| ISSN: | 1095-953X |