Ictal central apnoea is a feature of focal temporal seizures. It is implicated as a risk factor for sudden unexpected death in epilepsy (SUDEP). Here we study seizure-related apnoeas in two different models of experimental seizures, one chronic and one acute, in adult genetically-unmodified rats, to determine mechanisms of seizure-related apnoeas. Under general anaesthesia rats receive sensors for nasal temperature, hippocampal and/or neocortical potentials, and ECG or EMG for subsequent tethered video-telemetry. Tetanus neurotoxin (TeNT), injected into hippocampus during surgery, induces a chronic epileptic focus. Other implanted rats receive intraperitoneal pentylenetetrazol (PTZ) to evoke acute seizures. In chronically epileptic rats, convulsive seizures cause apnoeas (9.9 ± 5.3 s; 331 of 730 convulsive seizures in 15 rats), associated with bradyarrhythmias. Absence of EEG and ECG biomarkers exclude obstructive apnoeas. All eight TeNT-rats with diaphragm EMG have apnoeas with no evidence of obstruction, and have apnoea EMGs significantly closer to expiratory relaxation than inspiratory contraction during pre-apnoeic respiration, which we term "atonic diaphragm". Consistent with atonic diaphragm is that the pre-apnoeic nasal airflow is expiration, as it is in human ictal central apnoea. Two cases of rat sudden death occur. One, with telemetry to the end, reveals a lethal apnoea, the other only has video during the final days, which reveals cessation of breathing shortly after the last clonic epileptic movement. Telemetry following acute systemic PTZ reveals repeated seizures and seizure-related apnoeas, culminating in lethal apnoeas; ictal apnoeas are central - in 8 of 35 cases diaphragms initially contract tonically for 8.5 ± 15.0 s before relaxing, in the 27 remaining cases diaphragms are atonic throughout apnoeas. All terminal apnoeas are atonic. Differences in types of apnoea due to systemic PTZ in rats (mainly atonic) and mice (tonic) are likely species-specific. Certain genetic mouse models have apnoeas caused by tonic contraction, potentially due to expression of epileptogenic mutations throughout the brain, including in respiratory centres, in contrast with acquired focal epilepsies. We conclude that ictal apnoeas in the rat TeNT model result from atonic diaphragms. Relaxed diaphragms could be particularly helpful for therapeutic stimulation of the diaphragm to help restore respiration.

• MeSH
• apnoe patofyziologie   MeSH
• bránice * patofyziologie   MeSH
• chronická nemoc MeSH
• elektroencefalografie MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• pentylentetrazol toxicita   MeSH
• potkani Sprague-Dawley MeSH
• relaxace svalu fyziologie   MeSH
• tetanový toxin toxicita   MeSH
• záchvaty * patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Despite extensive temporal lobe epilepsy (TLE) research, understanding the specific limbic structures' roles in seizures remains limited. This weakness can be attributed to the complex nature of TLE and the existence of various TLE subsyndromes, including non-lesional TLE. Conventional TLE models like kainate and pilocarpine hinder precise assessment of the role of individual limbic structures in TLE ictogenesis due to widespread limbic damage induced by the initial status epilepticus. In this study, we used a non-lesional TLE model characterized by the absence of initial status and cell damage to determine the spatiotemporal profile of seizure initiation and limbic structure recruitment in TLE. Epilepsy was induced by injecting a minute dose of tetanus toxin into the right dorsal hippocampus in seven animals. Following injection, animals were implanted with bipolar recording electrodes in the amygdala, dorsal hippocampus, ventral hippocampus, piriform, perirhinal, and entorhinal cortices of both hemispheres. The animals were video-EEG monitored for four weeks. In total, 140 seizures (20 seizures per animal) were analyzed. The average duration of each seizure was 53.2+/-3.9 s. Seizure could initiate in any limbic structure. Most seizures initiated in the ipsilateral (41 %) and contralateral (18 %) ventral hippocampi. These two structures displayed a significantly higher probability of seizure initiation than by chance. The involvement of limbic structures in seizure initiation varied between individual animals. Surprisingly, only 7 % of seizures initiated in the injected dorsal hippocampus. The limbic structure recruitment into the seizure activity wasn't random and displayed consistent patterns of early recruitment of hippocampi and entorhinal cortices. Although ventral hippocampus represented the primary seizure onset zone, the study demonstrated the involvement of multiple limbic structures in seizure initiation in a non-lesional TLE model. The study also revealed the dichotomy between the primary epileptogenic lesion and main seizure onset zones and points to the central role of ventral hippocampi in temporal lobe ictogenesis.

• MeSH
• elektroencefalografie MeSH
• epilepsie temporálního laloku * chemicky indukované   patofyziologie   patologie   MeSH
• hipokampus účinky léků   patologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• potkani Sprague-Dawley MeSH
• tetanový toxin * toxicita   MeSH
• záchvaty * chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH