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. 2024 Aug:157:109848.
doi: 10.1016/j.yebeh.2024.109848. Epub 2024 May 31.

The latency to awake from induced-obstructive sleep apnea is reduced in rats with chronic epilepsy

Cláudio Quintino  1 , Milene R Malheiros-Lima  2 , Poliana Peres Ghazale  1 , Pedro Paulo Pereira Braga  1 , Octávio A C Maia  2 , Carlos Eduardo Gonçalves de Oliveira  3 , Felipe Waks Andrade  4 , Guus H Schoorlemmer  5 , Thiago S Moreira  2 , David Henriques da Matta  4 , Diego Basile Colugnati  1 , Aline Priscila Pansani  6
Affiliations

The latency to awake from induced-obstructive sleep apnea is reduced in rats with chronic epilepsy

Cláudio Quintino et al. Epilepsy Behav. 2024 Aug.

Abstract

OSA is known to increase the risk for SUDEP in persons with epilepsy, but the relationship between these two factors is not clear. Also, there is no study showing the acute responses to obstructive apnea in a chronic epilepsy model. Therefore, this study aimed to characterize cardiorespiratory responses to obstructive apnea and chemoreceptor stimulation in rats. In addition, we analyzed respiratory centers in the brain stem by immunohistochemistry. Epilepsy was induced with pilocarpine. About 30-60 days after the first spontaneous seizure, tracheal and thoracic balloons, and electrodes for recording the electroencephalogram, electromyogram, and electrocardiogram were implanted. Intermittent apneas were made by inflation of the tracheal balloon during wakefulness, NREM sleep, and REM sleep. During apnea, respiratory effort increased, and heart rate fell, especially with apneas made during wakefulness, both in control rats and rats with epilepsy. Latency to awake from apnea was longer with apneas made during REM than NREM, but rats with epilepsy awoke more rapidly than controls with apneas made during REM sleep. Rats with epilepsy also had less REM sleep. Cardiorespiratory responses to stimulation of carotid chemoreceptors with cyanide were similar in rats with epilepsy and controls. Immunohistochemical analysis of Phox2b, tryptophan hydroxylase, and NK1 in brain stem nuclei involved in breathing and sleep (retrotrapezoid nucleus, pre-Bötzinger complex, Bötzinger complex, and caudal raphe nuclei) revealed no differences between control rats and rats with epilepsy. In conclusion, our study showed that rats with epilepsy had a decrease in the latency to awaken from apneas during REM sleep, which may be related to neuroplasticity in some other brain regions related to respiratory control, awakening mechanisms, and autonomic modulation.

Keywords: Bötzinger; Peripheral chemoreflex; Pilocarpine; Pré-Bötzinger; RTN; Raphe nuclei.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.