Genetic susceptibility to epilepsy is not enough to trigger severe respiratory changes during early development in rats

Abstract

Epilepsy is a neurological disease characterized by the recurrence of seizures. Seizures are associated with respiratory suppression and apneas that can increase the risk of death. The highest prevalence of seizures occurs during childhood, however, respiratory changes related to seizures during development are unknown. It is also unknown whether genetic susceptibility to epilepsy itself induces respiratory changes. Thus, the objective of this study is to test the hypothesis that animals genetically susceptible to epilepsy (Wistar Audiogenic Rats, WAR) present respiratory alterations in the neonatal period, defined as presence of apneas and attenuation of ventilatory responses to hypercapnia and hypoxia. Specifically, we hypothesize that the respiratory alterations in these animals precede the occurrence of seizures. For this study, we used WAR and Wistar rats (males and females) in three developmental windows P1-3 (P, postnatal days), P12-14 and P21-23, and in adulthood (>60 days old). Pulmonary ventilation in room air and during hypercapnia (7%CO2) or hypoxia (10%O2) was measured by pressure (P1-3) or whole-body plethysmography (P12-14, P21- 23 and adults). Our results showed that under room air conditions, WAR animals had a higher number of apneas at P1-3 (9.60±3.0 event/15min) compared to the Wistar group (4.55±0.7 event/15min), but not at the other ages studied. The ventilatory response to hypercapnia was not significantly different between the Wistar and WAR groups during development (P1-3: 185.1±12.9 vs 170.5±8; P12-14: 174.7±8.7 vs 159.3±11.2; P21-23: 229.6±16.7 vs 221.5±25.0 VE% at baseline; Wistar vs WAR, respectively). Moreover, the ventilatory response to hypercapnia was attenuated in adult WAR animals only after seizure induced by acoustic stimuli (210±30 vs 150±30 VE% at baseline, Pre-Acoustic Stimuli vs Post Acoustic Stimuli, respectively, P<0.05). The ventilatory response to hypoxia of WAR rats was lower only at P1-3 (127.0±7.8%VE at baseline) when compared to Wistar (168.8±14.6%, P<0.05), but not at P12-14 (127.2±7.4 vs 124.0±6.4) and P21-23 (170.0±18.5 vs 175.6±16.5; Wistar vs WAR, respectively). Overall, the results suggest that genetic susceptibility to epilepsy confers respiratory alterations in early life (P1-3), such as higher occurrence of apneas and attenuated VE response to hypoxia. These alterations disappear during development. Moreover, no difference in CO2 chemoreflex was observed in WAR across ages, suggesting that the impairment of hypercapnic ventilatory responses depends on audiogenic seizure Acknowledgments: financial support; FAPEMIG and CNPq This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.