Journal article
The effect of time‐of‐day and circadian phase on vulnerability to seizure‐induced death in two mouse models
The Journal of physiology, Vol.599(6), pp.1885-1899
03/15/2021
DOI: 10.1113/JP280856
PMCID: PMC9365197
PMID: 33501667
Abstract
Key points
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of premature death in patients with refractory epilepsy.
SUDEP typically occurs during the night, although the reason for this is unclear.
We found that, in normally entrained mice, time‐of‐day alters vulnerability to seizure‐induced death.
We found that, in free‐running mice, circadian phase alters the vulnerability to seizure‐induced death.
These findings suggest that circadian rhythmicity may be responsible for the increased night‐time prevalence of SUDEP
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy‐related death. SUDEP typically occurs during the night following a seizure. Many aspects of mammalian physiology are regulated by circadian rhythms in ways that might make seizures occuring during the night more dangerous. Using two mouse models of seizure‐induced death, we demonstrate that time‐of‐day and circadian rhythms alter vulnerability to seizure‐induced death. We exposed normally entrained DBA/1 mice to a potentially seizure‐inducing acoustic stimulus at different times of day and compared the characteristics and outcomes of the seizures. Time‐of‐day did not alter the probability of a seizure but it did alter the probability of seizure‐induced death. To determine whether circadian rhythms alter vulnerability to seizure‐induced death, we induced maximal electroshock seizures in free‐running C57BL/6J mice at different circadian time points at the same time as measuring breathing via whole body plethysmography. Circadian phase did not affect seizure severity but it did alter postictal respiratory outcomes and the probability of seizure‐induced death. By contrast to our expectations, in entrained and free‐running mice, vulnerability to seizure‐induced death was greatest during the night and subjective night, respectively. These findings suggest that circadian rhythmicity may be responsible for the increased night‐time prevalence of SUDEP and that the underlying mechanism is phase conserved between nocturnal and diurnal mammals. All of the seizures in the present study were induced during wakefulness, indicating that the effect of time point on vulnerability to seizure‐induced death was not the result of sleep. Understanding why SUDEP occurs more frequently during the night may inform future preventative countermeasures.
Key points
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of premature death in patients with refractory epilepsy.
SUDEP typically occurs during the night, although the reason for this is unclear.
We found that, in normally entrained mice, time‐of‐day alters vulnerability to seizure‐induced death.
We found that, in free‐running mice, circadian phase alters the vulnerability to seizure‐induced death.
These findings suggest that circadian rhythmicity may be responsible for the increased night‐time prevalence of SUDEP
Details
- Title: Subtitle
- The effect of time‐of‐day and circadian phase on vulnerability to seizure‐induced death in two mouse models
- Creators
- Benton S Purnell - University of IowaAlexandra N Petrucci - University of IowaRui Li - University of IowaGordon F Buchanan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.599(6), pp.1885-1899
- DOI
- 10.1113/JP280856
- PMID
- 33501667
- PMCID
- PMC9365197
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Number of pages
- 15
- Grant note
- NIH/NINDS (T32NS007421; F31NS106819; R01NS095842)
- Language
- English
- Date published
- 03/15/2021
- Academic Unit
- Neurology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984070144702771
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