海马扩张性去极化作为后脑活动的驱动因素

IF 14.6 1区 医学 Q1 CELL BIOLOGY
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
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引用次数: 0

摘要

癫痫发作后(后)症状是癫痫患者经常遇到的,可能危及生命,但其神经生物学基础仍未得到充分研究。利用双光子或宽视场成像、场电位和单位记录、光遗传学和基本行为评估,我们研究了健康状态或病毒性脑炎小鼠的癫痫发作和阳性症状。我们显示海马倾向于癫痫相关的扩张性去极化(sSD)。通过光遗传刺激,我们提供的证据表明,诱导的孤立海马SD足以引发后脑活动(PIA),而诱导的孤立癫痫样发作则不会。此外,PIA发生在没有SD进展到新皮层的情况下。此外,我们分析了4例局灶性癫痫患者的Behnke-Fried深度电极记录。在13例记录的癫痫发作中,我们在区域分析中观察到癫痫发作终止时的5次缓慢变化可以反映假定的sSD。为了支持我们在小鼠身上的实验,我们还发现人类颞叶系统(海马体和杏仁核)对这种现象的脆弱性增加,与未受影响的大脑区域相比,受影响的大脑区域恢复时间更长。这项工作表明,sSD是一种以前未被充分认识的癫痫患者明显阳性症状的病理临床实体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
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.
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