Authors :
Presenting Author: Elise Collard, PhD student – Université Catholique de Louvain
Enrique Germany Morrison, PhD – Université catholique de Louvain
Antoine Nonclercq, PhD – Université Libre de Bruxelles
Riëm El Tahry, MD, PhD – Université Catholique de Louvain, Clinique Universitaire ST Luc
Rationale:
Previous findings from our lab showed that vagus nerve activity (VNA) during absence seizures in GAERS rats varies with the cumulative effect of seizures, suggesting a potential marker for parasympathetic dysfunction (Collard et al; under revision). The autonomic nervous system—including parasympathetic output via the vagus nerve—is strongly regulated by circadian rhythms, which modulate heart rate variability, blood pressure, and respiratory patterns across the sleep–wake cycle(Baker & Kimpinski, 2021; Cabiddu et al., 2012). These rhythms are crucial for maintaining physiological homeostasis and stress resilience. In epilepsy, circadian disruption has been associated with increased seizure susceptibility and autonomic dysregulation (Karoly et al., 2017; Smyk & Luijtelaar, 2020). Moreover, hypercapnic challenges—used to model respiratory disturbances such as apnea—can unmask abnormal autonomic responses in epileptic models, potentially reflecting vagal impairment or sympathetic overcompensation, both implicated in SUDEP pathophysiology(Devinsky, 2011). Assessing VNA across sleep–wake states and following hypercapnia may thus reveal autonomic deficits, shedding light on the interaction between respiratory stress, seizure dynamics, and circadian control in epilepsy. Methods:
Freely moving healthy rats (n=7) were implanted with epidural EEG electrodes ([GND]: AP: -2, ML: +-3 [PL/PR]: AP: 5, ML: +-3 [REF]: AP: -6, ML: 0) and intraneural/control vagus nerve electrodes using PFA-coated platinum wire (segment inserted into the nerve was left uncoated) under sevoflurane anesthesia. Recordings were conducted continuously for 24h, followed by a 3-hour session including baseline, 10% CO₂ exposure, and recovery. VNA was segmented into NREM sleep and active states, and compound action potentials (CAPs) were detected via local maxima thresholding. Neural-specific spikes were isolated by excluding events shared with control electrodes. The same protocol is underway in GAERS rats (n=7).Results:
Healthy rats exhibited significantly higher CAPs density during NREM sleep compared to active periods, indicating that chronic VNA recordings can reflect circadian parasympathetic modulation. Following hypercapnia, CAPs density increased significantly during recovery, suggesting intact vagal reactivity to respiratory stress.
Conclusions:
These findings support VNA as a promising biomarker for circadian and hypercapnic-related autonomic modulation. Ongoing comparisons with GAERS rats may clarify autonomic deficits underlying SUDEP risk and help develop responsive strategies for epilepsy management in VNS-treated patients.
Funding:
Welbio, FNRS-FRIA