Labastida-Ramirez, Alejandro;
Codadu, Neela K;
Agan, Kagan;
Wykes, Robert C;
(2025)
State-of-the-art preclinical techniques to study the impact of spreading depolarizations in awake rodents.
The Journal of Headache and Pain
, 26
(1)
, Article 188. 10.1186/s10194-025-02121-0.
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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.
| Type: | Article |
|---|---|
| Title: | State-of-the-art preclinical techniques to study the impact of spreading depolarizations in awake rodents |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s10194-025-02121-0 |
| Publisher version: | https://doi.org/10.1186/s10194-025-02121-0 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Anesthesia, Cortical spreading depolarization, DC-coupled electrophysiology, Functional ultrasound, Migraine, Optogenetics, Wireless telemetry, Animals, Cortical Spreading Depression, Disease Models, Animal, Wakefulness, Rodentia, Brain |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10213076 |
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