Chiang Chia-Chu, Kotamraju B P, Durand Dominique M
Department of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland, Ohio, USA.
Epilepsia Open. 2025 Jul 18. doi: 10.1002/epi4.70060.
Seizure-induced bradycardia and asystole have been documented by video-EEG monitoring periods in patients with epilepsy. This cardiac dysfunction during or after seizures may contribute to sudden unexpected death in epilepsy (SUDEP). Abnormal neurocardiac function during seizures could potentially be caused by seizures propagating to the brainstem, passing through the parasympathetic nerve and disrupting cardiac control networks.
We simultaneously recorded activity from the brain and vagus nerve as well as heart rate and respiration in adult Sprague-Dawley rats under urethane anesthesia. Neural activity in the brain was recorded using carbon nanotube yarn (CNTY) electrodes implanted in the hippocampal CA3 region, the motor cortex (M1), and the nucleus ambiguus in the brainstem. Additionally, two CNTY electrodes were implanted in the vagus nerve to monitor its activity. ECG electrodes and an accelerometer were also implanted to record heart rate and respiration. Seizures were induced by injecting 4-AP into the hippocampal CA3 region. Following the injection, all signals were recorded and stored for analysis to study the interactions among these regions during seizures.
Local 4-AP injection successfully induced intermittent seizures in the hippocampus and cortex, with some seizures propagating into the nucleus ambiguus. When seizures invaded the nucleus ambiguus, the heart rate dropped following the onset of the seizures and returned to baseline during the seizures. The heart rate variability also increased significantly during the seizures. Furthermore, vagus nerve activity increased significantly by 0.21 ± 0.08 μV following the seizures propagating to the brainstem.
Our findings indicate increased activity in the nucleus ambiguus during seizures can induce bradycardia through the vagus nerve. These changes in cardiac function via the autonomic nervous system could contribute to the instability of the autonomic control system during seizures and potentially explain one of the possible mechanisms underlying sudden unexpected death in epilepsy (SUDEP).
This study investigates how seizures affect heart function and may contribute to sudden unexpected death in epilepsy (SUDEP). We studied the brain, vagus nerve, and heart rate in anesthetized rats. Seizures were triggered in the hippocampus, and recordings showed that when seizures spread to the nucleus ambiguus in the brainstem region, the heart rate dropped and became more irregular. The vagus nerve, which helps regulate heart function, also became more active. These findings suggest that seizures can disrupt heart control by affecting the autonomic nervous system, which may help explain one of the possible mechanisms of how SUDEP occurs.
癫痫患者在视频脑电图监测期间已记录到癫痫发作诱发的心动过缓和心搏停止。癫痫发作期间或之后的这种心脏功能障碍可能导致癫痫性猝死（SUDEP）。癫痫发作期间异常的神经心脏功能可能是由癫痫发作传播到脑干、通过副交感神经并破坏心脏控制网络引起的。
在乌拉坦麻醉下，我们同时记录成年Sprague-Dawley大鼠的脑和迷走神经活动以及心率和呼吸。使用植入海马CA3区、运动皮层（M1）和脑干疑核的碳纳米管纱（CNTY）电极记录脑内神经活动。此外，在迷走神经中植入两个CNTY电极以监测其活动。还植入了心电图电极和加速度计以记录心率和呼吸。通过向海马CA3区注射4-氨基吡啶（4-AP）诱发癫痫发作。注射后，记录并存储所有信号以进行分析，以研究癫痫发作期间这些区域之间的相互作用。
局部注射4-AP成功诱发海马和皮层的间歇性癫痫发作，一些癫痫发作传播到疑核。当癫痫发作侵入疑核时，心率在癫痫发作开始后下降，并在癫痫发作期间恢复到基线。癫痫发作期间心率变异性也显著增加。此外，癫痫发作传播到脑干后，迷走神经活动显著增加0.21±0.08μV。
我们的研究结果表明，癫痫发作期间疑核活动增加可通过迷走神经诱发心动过缓。通过自主神经系统的这些心脏功能变化可能导致癫痫发作期间自主控制系统的不稳定，并可能解释癫痫性猝死（SUDEP）潜在的可能机制之一。
本研究调查癫痫发作如何影响心脏功能以及可能导致癫痫性猝死（SUDEP）。我们研究了麻醉大鼠的脑、迷走神经和心率。在海马中引发癫痫发作，记录显示当癫痫发作扩散到脑干区域的疑核时，心率下降且变得更加不规则。有助于调节心脏功能的迷走神经也变得更加活跃。这些发现表明癫痫发作可通过影响自主神经系统扰乱心脏控制，这可能有助于解释SUDEP发生的可能机制之一。
