State-of-the-art preclinical techniques to study the impact of spreading depolarizations in awake rodents.

IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY
Alejandro Labastida-Ramirez, Neela K Codadu, Kagan Agan, Robert C Wykes
{"title":"State-of-the-art preclinical techniques to study the impact of spreading depolarizations in awake rodents.","authors":"Alejandro Labastida-Ramirez, Neela K Codadu, Kagan Agan, Robert C Wykes","doi":"10.1186/s10194-025-02121-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Understanding the mechanisms of pathological brain network activity and the efficacy of therapies requires testing hypothesis in vivo, where brain circuitry remains preserved. Therefore, animal models are a key tool in the study of primary neurological disorders such as migraine, stroke and epilepsy. These models not only have advanced our understanding of the underlying neurobiology of these disorders but have also provided novel pharmacological targets and insights on shared pathophysiological processes such as spreading depolarizations (SD). SD, the electrographic correlate of migraine with aura, are transient waves of near-complete neuroglial depolarization associated with transmembrane ionic and water shifts. BODY: Many studies investigating the impact of SD in preclinical models have done so in the presence of anesthesia. However, the use of anesthesia is a well-known confounding factor that not only influences SD threshold or frequency but also SD-evoked hemodynamic responses as common anesthetics affect cerebral blood flow and neurovascular coupling, limiting translation. Therefore, here we discuss research methods that have recently been developed or refined to allow the study of SD in awake rodents with a focus on migraine with aura. We discuss advantages, limitations and also efforts made to transition towards minimally-invasive procedures. Methods include optogenetic approaches to induce SD, multisite high-fidelity DC-coupled electrophysiological recordings, and measurements of neurovascular signals detected at both mesoscopic/macroscopic (e.g., fluorescent reporters, functional ultrasound system) and microscopic levels (e.g., two-photon microscopy, miniscopes). Additionally, we discuss continuous wireless telemetry recordings to detect spontaneous SD frequency over weeks to months in freely moving animals.</p><p><strong>Conclusion: </strong>Implementation of these methods in awake brain will close the translational gap and improve the relevance of preclinical animal models.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"188"},"PeriodicalIF":7.9000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395755/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Headache and Pain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10194-025-02121-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Understanding the mechanisms of pathological brain network activity and the efficacy of therapies requires testing hypothesis in vivo, where brain circuitry remains preserved. Therefore, animal models are a key tool in the study of primary neurological disorders such as migraine, stroke and epilepsy. These models not only have advanced our understanding of the underlying neurobiology of these disorders but have also provided novel pharmacological targets and insights on shared pathophysiological processes such as spreading depolarizations (SD). SD, the electrographic correlate of migraine with aura, are transient waves of near-complete neuroglial depolarization associated with transmembrane ionic and water shifts. BODY: Many studies investigating the impact of SD in preclinical models have done so in the presence of anesthesia. However, the use of anesthesia is a well-known confounding factor that not only influences SD threshold or frequency but also SD-evoked hemodynamic responses as common anesthetics affect cerebral blood flow and neurovascular coupling, limiting translation. Therefore, here we discuss research methods that have recently been developed or refined to allow the study of SD in awake rodents with a focus on migraine with aura. We discuss advantages, limitations and also efforts made to transition towards minimally-invasive procedures. Methods include optogenetic approaches to induce SD, multisite high-fidelity DC-coupled electrophysiological recordings, and measurements of neurovascular signals detected at both mesoscopic/macroscopic (e.g., fluorescent reporters, functional ultrasound system) and microscopic levels (e.g., two-photon microscopy, miniscopes). Additionally, we discuss continuous wireless telemetry recordings to detect spontaneous SD frequency over weeks to months in freely moving animals.

Conclusion: Implementation of these methods in awake brain will close the translational gap and improve the relevance of preclinical animal models.

Abstract Image

Abstract Image

Abstract Image

最先进的临床前技术来研究在清醒的啮齿动物中传播去极化的影响。
背景:了解病理性脑网络活动的机制和治疗效果需要在体内测试假设,其中脑回路仍然保存。因此,动物模型是研究偏头痛、中风和癫痫等原发性神经系统疾病的关键工具。这些模型不仅提高了我们对这些疾病的潜在神经生物学的理解,而且还提供了新的药理学靶点和对诸如扩张性去极化(SD)等共同病理生理过程的见解。SD,偏头痛与先兆的电图关联,是与跨膜离子和水转移相关的神经胶质近乎完全去极化的瞬态波。许多在临床前模型中研究SD影响的研究都是在麻醉的情况下进行的。然而,麻醉剂的使用是一个众所周知的混杂因素,它不仅影响SD阈值或频率,还会影响SD诱发的血流动力学反应,因为普通麻醉剂会影响脑血流和神经血管耦合,限制了翻译。因此,我们在这里讨论了最近开发或改进的研究方法,以允许对清醒啮齿动物的SD进行研究,重点是先兆偏头痛。我们讨论的优势,局限性和努力过渡到微创程序。方法包括光遗传学方法诱导SD,多位点高保真直流耦合电生理记录,以及在介观/宏观(如荧光报告,功能超声系统)和微观水平(如双光子显微镜,微型显微镜)检测到的神经血管信号的测量。此外,我们讨论了连续的无线遥测记录,以检测自由移动动物数周至数月的自发SD频率。结论:这些方法在清醒脑中的实施将弥补翻译空白,提高临床前动物模型的相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Headache and Pain
Journal of Headache and Pain 医学-临床神经学
CiteScore
11.80
自引率
13.50%
发文量
143
审稿时长
6-12 weeks
期刊介绍: The Journal of Headache and Pain, a peer-reviewed open-access journal published under the BMC brand, a part of Springer Nature, is dedicated to researchers engaged in all facets of headache and related pain syndromes. It encompasses epidemiology, public health, basic science, translational medicine, clinical trials, and real-world data. With a multidisciplinary approach, The Journal of Headache and Pain addresses headache medicine and related pain syndromes across all medical disciplines. It particularly encourages submissions in clinical, translational, and basic science fields, focusing on pain management, genetics, neurology, and internal medicine. The journal publishes research articles, reviews, letters to the Editor, as well as consensus articles and guidelines, aimed at promoting best practices in managing patients with headaches and related pain.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信