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Because of its involvement in breathing control and neuronal excitability, dysregulation of the serotonin (5‐HT) 2C receptor (5‐HT2C) might play a key role in sudden unexpected death in epilepsy. Seizure‐induced respiratory arrest is thus prevented by a 5‐HT2B/C agonist in different seizure model. However, the specific contribution of 5‐HT2C in chronic epilepsy‐related respiratory dysfunction remains unknown. In a rat model of temporal lobe epilepsy (EPI rats), in which we previously reported interictal respiratory dysfunctions and a reduction of brainstem 5‐HT tone, quantitative reverse transcriptase polymerase chain reaction showed overexpression of TPH2 (5‐HT synthesis enzyme), SERT (5‐HT reuptake transporter), and 5‐HT2C transcript levels in the brainstem of EPI rats, and of RNA‐specific adenosine deaminase (ADAR1, ADAR2) involved in the production of 5‐HT2C isoforms. Interictal ventilation was assessed with whole‐body plethysmography before and 2 h after administration of SB242084 (2 mg/kg), a specific antagonist of 5‐HT2C. As expected, SB242084 administration induced a progressive decrease in ventilatory parameters and an alteration of breathing stability in both control and EPI rats. However, the size of the SB242084 effect was lower in EPI rats than in controls. Increased 5‐HT2C gene expression in the brainstem of EPI rats could be part of a compensatory mechanism against epilepsy‐related low 5‐HT tone and expression of 5‐HT2C isoforms for which 5‐HT affinity might be lower. [ABSTRACT FROM AUTHOR]

Seasonal and zonal climatologies of Rayleigh–Taylor growth rates under geomagnetically quiet conditions during solar minimum and solar moderate conditions as a function of local time and altitude are calculated using open source data and software. It is under the action of the Rayleigh–Taylor instability that plumes of depleted plasma, or plasma bubbles, are understood to develop in the bottomside of the equatorial ionosphere. The growin python module utilizes other Heliophysics python modules to collate and process vertical plasma drift to drive the SAMI2 is Another Model of the Ionosphere (SAMI2) model and subsequently calculate the flux tube integrated Rayleigh–Taylor growth rate. The process is repeated for two different types of drift inputs: the Fejer–Scherliess model and measured drifts from the Communication/Navigation Outage Forecasting System (C/NOFS). These growth rates are compared to bubble occurrence frequencies obtained from a dataset of bubbles detected by the C/NOFS satellite. There is an agreement between periods of strong positive instability growth and high frequencies of bubble occurrence in both low and moderate solar activity conditions when using C/NOFS drifts. Fejer–Scherliess drifts are only in agreement with bubble occurrence frequencies during moderate solar activity conditions. Bubble occurrence frequencies are often above 25%, even when growth rates in the bottomside F region are negative. The climatological nature of the growth rates discussed here begs further study into the day-to-day variability of the growth rate and its drivers.

Although animal models have helped to elaborate meaningful hypotheses about the pathophysiology of sudden and unexpected death in epilepsy (SUDEP), specific prevention strategies are still lacking, potentially reflecting the limitations of these models and the intrinsic difficulties of investigating SUDEP. The interpretation of preclinical data and their translation to diagnostic and therapeutic developments in patients thus require a high level of confidence in their relevance to model the human situation. Preclinical models of SUDEP are heterogeneous and include rodent and nonrodent species. A critical aspect is whether the animals have isolated seizures exclusively induced by a specific trigger, such as models where seizures are elicited by electrical stimulation, pharmacological intervention, or DBA mouse strains, or whether they suffer from epilepsy with spontaneous seizures, with or without spontaneous SUDEP, either of nongenetic epilepsy etiology or from genetically based developmental and epileptic encephalopathies. All these models have advantages and potential disadvantages, but it is important to be aware of these limitations to interpret data appropriately in a translational perspective. The majority of models with spontaneous seizures are of a genetic basis, whereas SUDEP cases with a genetic basis represent only a small proportion of the total number. In almost all models, cardiorespiratory arrest occurs during the course of the seizure, contrary to that in patients observed at the time of death, potentially raising the issue of whether we are studying models of SUDEP or models of periseizure death. However, some of these limitations are impossible to avoid and can in part be dependent on specific features of SUDEP, which may be difficult to model. Several preclinical tools are available to address certain gaps in SUDEP pathophysiology, which can be used to further validate current preclinical models. [ABSTRACT FROM AUTHOR]