Journal article
Determining the Spread: Potential Biomarkers and Treatment for Seizure-Induced-Spreading Depolarization in a Mouse Model of Genetic Epilepsy
Epilepsy currents, Vol.24(1), pp.47-49
02/2024
DOI: 10.1177/15357597231212763
PMCID: PMC10846522
PMID: 38327539
Abstract
A Hyperthermic Seizure Unleashes a Surge of Spreading Depolarizations in Scn1a-Deficient Mice
Aiba I, Ning Y, Noebels JL. JCI Insight. 2023;8(15):e170399. doi:https://doi.org/10.1172/jci.insight.170399
Spreading depolarization (SD) is a massive wave of cellular depolarization that slowly migrates across the brain gray matter. Cortical SD is frequently generated following brain injury, while less is understood about its potential contribution to genetic disorders of hyperexcitability, such as SCN1A-deficient epilepsy, in which febrile seizure often contributes to disease initiation. Here we report that spontaneous SD waves are predominant EEG abnormalities in the Scn1a-deficient mouse (Scn1a+/R1407X) and undergo sustained intensification following a single hyperthermic seizure. Chronic DC-band EEG recording detected spontaneous SDs, seizures, and seizure-SD complexes in Scn1a+/R1407X mice but not WT littermates. The SD events were infrequent, while a single hyperthermia-induced seizure robustly increased SD frequency over 4-fold during the initial postictal week. This prolonged neurological aftermath could be suppressed by memantine administration. Video, electromyogram, and EEG spectral analysis revealed distinct neurobehavioral patterns; individual seizures were associated with increased motor activities, while SDs were generally associated with immobility. We also identified a stereotypic SD prodrome, detectable over a minute before the onset of the DC potential shift, characterized by increased motor activity and bilateral EEG frequency changes. Our study suggests that cortical SD is a pathological manifestation in SCN1A-deficient epileptic encephalopathy.
Details
- Title: Subtitle
- Determining the Spread: Potential Biomarkers and Treatment for Seizure-Induced-Spreading Depolarization in a Mouse Model of Genetic Epilepsy
- Creators
- Katelyn G. Joyal - University of IowaGordon F. Buchanan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Epilepsy currents, Vol.24(1), pp.47-49
- DOI
- 10.1177/15357597231212763
- PMID
- 38327539
- PMCID
- PMC10846522
- NLM abbreviation
- Epilepsy Curr
- ISSN
- 1535-7597
- eISSN
- 1535-7511
- Language
- English
- Electronic publication date
- 11/22/2023
- Date published
- 02/2024
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984539528702771
Metrics
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