Bence Mitlasóczki, Adrián Gutiérrez Gómez, Midia Kamali, Natalia Babushkina, Mayan Baues, Laura Kück, André Nathan Haubrich, Theodoros Tamiolakis, Annika Breuer, Simon Granak, Merlin Schwering-Sohnrey, Ingo Gerhauser, Wolfgang Baumgärtner, Martin Karl Schwarz, Laura Ewell, Thoralf Opitz, Julika Pitsch, Simon Musall, Rainer Surges, Florian Mormann, Heinz Beck, Michael Wenzel
{"title":"海马扩张性去极化作为后脑活动的驱动因素","authors":"Bence Mitlasóczki, Adrián Gutiérrez Gómez, Midia Kamali, Natalia Babushkina, Mayan Baues, Laura Kück, André Nathan Haubrich, Theodoros Tamiolakis, Annika Breuer, Simon Granak, Merlin Schwering-Sohnrey, Ingo Gerhauser, Wolfgang Baumgärtner, Martin Karl Schwarz, Laura Ewell, Thoralf Opitz, Julika Pitsch, Simon Musall, Rainer Surges, Florian Mormann, Heinz Beck, Michael Wenzel","doi":"10.1126/scitranslmed.adv3260","DOIUrl":null,"url":null,"abstract":"<div >Postseizure (postictal) symptoms are regularly encountered in epilepsy and can be life threatening, yet their neurobiological underpinnings remain understudied. Using two-photon or widefield imaging, field potential and unit recordings, optogenetics, and basic behavioral assessment under healthy conditions or viral encephalitis, we studied seizures and postictal symptoms in mice. We show a propensity of the hippocampus for seizure-associated spreading depolarization (sSD). Through optogenetic stimulation, we provide evidence that induced isolated hippocampal SD is sufficient to elicit postictal ambulation (PIA), whereas induced isolated seizure-like episodes are not. Furthermore, PIA occurred in the absence of SD progression to the neocortex. In addition, we analyzed Behnke-Fried depth-electrode recordings in four patients with focal epilepsy. Of 13 recorded seizures, we observed five slow shifts at seizure termination in the regionwise analysis that could reflect putative sSD. In support of our experiments in mice, we also found an increased vulnerability of the human temporomesial system (hippocampus and amygdala) for this phenomenon and longer recovery times of affected as compared with nonaffected brain regions. This work suggests sSD as a previously underrecognized pathoclinical entity underlying distinct postictal symptoms in epilepsy.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 816","pages":""},"PeriodicalIF":14.6000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hippocampal spreading depolarization as a driver of postictal ambulation\",\"authors\":\"Bence Mitlasóczki, Adrián Gutiérrez Gómez, Midia Kamali, Natalia Babushkina, Mayan Baues, Laura Kück, André Nathan Haubrich, Theodoros Tamiolakis, Annika Breuer, Simon Granak, Merlin Schwering-Sohnrey, Ingo Gerhauser, Wolfgang Baumgärtner, Martin Karl Schwarz, Laura Ewell, Thoralf Opitz, Julika Pitsch, Simon Musall, Rainer Surges, Florian Mormann, Heinz Beck, Michael Wenzel\",\"doi\":\"10.1126/scitranslmed.adv3260\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >Postseizure (postictal) symptoms are regularly encountered in epilepsy and can be life threatening, yet their neurobiological underpinnings remain understudied. Using two-photon or widefield imaging, field potential and unit recordings, optogenetics, and basic behavioral assessment under healthy conditions or viral encephalitis, we studied seizures and postictal symptoms in mice. We show a propensity of the hippocampus for seizure-associated spreading depolarization (sSD). Through optogenetic stimulation, we provide evidence that induced isolated hippocampal SD is sufficient to elicit postictal ambulation (PIA), whereas induced isolated seizure-like episodes are not. Furthermore, PIA occurred in the absence of SD progression to the neocortex. In addition, we analyzed Behnke-Fried depth-electrode recordings in four patients with focal epilepsy. Of 13 recorded seizures, we observed five slow shifts at seizure termination in the regionwise analysis that could reflect putative sSD. In support of our experiments in mice, we also found an increased vulnerability of the human temporomesial system (hippocampus and amygdala) for this phenomenon and longer recovery times of affected as compared with nonaffected brain regions. This work suggests sSD as a previously underrecognized pathoclinical entity underlying distinct postictal symptoms in epilepsy.</div>\",\"PeriodicalId\":21580,\"journal\":{\"name\":\"Science Translational Medicine\",\"volume\":\"17 816\",\"pages\":\"\"},\"PeriodicalIF\":14.6000,\"publicationDate\":\"2025-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/scitranslmed.adv3260\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/scitranslmed.adv3260","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Hippocampal spreading depolarization as a driver of postictal ambulation
Postseizure (postictal) symptoms are regularly encountered in epilepsy and can be life threatening, yet their neurobiological underpinnings remain understudied. Using two-photon or widefield imaging, field potential and unit recordings, optogenetics, and basic behavioral assessment under healthy conditions or viral encephalitis, we studied seizures and postictal symptoms in mice. We show a propensity of the hippocampus for seizure-associated spreading depolarization (sSD). Through optogenetic stimulation, we provide evidence that induced isolated hippocampal SD is sufficient to elicit postictal ambulation (PIA), whereas induced isolated seizure-like episodes are not. Furthermore, PIA occurred in the absence of SD progression to the neocortex. In addition, we analyzed Behnke-Fried depth-electrode recordings in four patients with focal epilepsy. Of 13 recorded seizures, we observed five slow shifts at seizure termination in the regionwise analysis that could reflect putative sSD. In support of our experiments in mice, we also found an increased vulnerability of the human temporomesial system (hippocampus and amygdala) for this phenomenon and longer recovery times of affected as compared with nonaffected brain regions. This work suggests sSD as a previously underrecognized pathoclinical entity underlying distinct postictal symptoms in epilepsy.
期刊介绍:
Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research.
The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases.
The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine.
The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.