Journal article
Effect of adenosinergic manipulations on amygdala‐kindled seizures in mice: Implications for sudden unexpected death in epilepsy
Epilepsia (Copenhagen), Vol.65(9), pp.2812-2826
09/2024
DOI: 10.1111/epi.18059
PMCID: PMC11534534
PMID: 38980980
Appears in UI Libraries Support Open Access
Abstract
Objective Sudden unexpected death in epilepsy (SUDEP) results in more years of potential life lost than any neurological condition with the exception of stroke. It is generally agreed that SUDEP happens due to some form of respiratory, cardiac, and electrocerebral dysfunction following a seizure; however, the mechanistic cause of these perturbations is unclear. One possible explanation lies with adenosinergic signaling. Extracellular levels of the inhibitory neuromodulator adenosine rapidly rise during seizures, a countermeasure that is necessary for seizure termination. Previous evidence has suggested that excessive adenosinergic inhibition could increase the risk of SUDEP by silencing brain areas necessary for life, such as the respiratory nuclei of the brainstem. The goal of this investigation was to further clarify the role of adenosine in seizure‐induced respiratory and electrocerebral dysfunction. Methods To determine the role of adenosine in postictal physiological dysregulation, we pharmacologically manipulated adenosine signaling prior to amygdala‐kindled seizures in mice while recording electroencephalogram (EEG), electromyogram, and breathing using whole body plethysmography. The adenosinergic drugs used in this study included selective and nonselective adenosine receptor antagonists and inhibitors of adenosine metabolism. Results We found that high doses of adenosine receptor antagonists caused some seizures to result in seizure‐induced death; however, counterintuitively, animals in these conditions that did not experience seizure‐induced death had little or no postictal generalized EEG suppression. Inhibitors of adenosine metabolism had no effect on postictal breathing but did worsen some postictal electrocerebral outcomes. Significance The unexpected effect of high doses of adenosine antagonists on seizure‐induced death observed in this study may be due to the increase in seizure severity, vasoconstriction, or phosphodiesterase inhibition caused by these drugs at high doses. These findings further clarify the role of adenosine in seizure‐induced death and may have implications for the consumption of caffeine in epilepsy patients and the prevention of SUDEP.
Details
- Title: Subtitle
- Effect of adenosinergic manipulations on amygdala‐kindled seizures in mice: Implications for sudden unexpected death in epilepsy
- Creators
- Benton S. Purnell - University of IowaAlexandra N. Petrucci - University of IowaRui Li - University of Iowa, NeurologyGordon F. Buchanan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Epilepsia (Copenhagen), Vol.65(9), pp.2812-2826
- DOI
- 10.1111/epi.18059
- PMID
- 38980980
- PMCID
- PMC11534534
- NLM abbreviation
- Epilepsia
- ISSN
- 0013-9580
- eISSN
- 1528-1167
- Publisher
- Wiley
- Grant note
- National Institute of Neurological Disorders and Stroke. Grant Numbers: F31NS106819, R01NS095842, T32NS007421
- Language
- English
- Electronic publication date
- 07/09/2024
- Date published
- 09/2024
- Academic Unit
- Neurology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984656659602771
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