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

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dc.authoridWykes, Robert/0000-0002-6141-6822;
dc.contributor.authorLabastida-Ramirez, Alejandro
dc.contributor.authorCodadu, Neela K.
dc.contributor.authorAgan, Kagan
dc.contributor.authorWykes, Robert C.
dc.date.accessioned2025-10-11T20:48:10Z
dc.date.available2025-10-11T20:48:10Z
dc.date.issued2025
dc.departmentDüzce Üniversitesien_US
dc.description.abstractBackgroundUnderstanding 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.BodyMany 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.ConclusionImplementation of these methods in awake brain will close the translational gap and improve the relevance of preclinical animal models.en_US
dc.description.sponsorshipMedical Research Councilen_US
dc.description.sponsorshipWe are customers of Open Source Instruments, Inc., with no financial or professional affiliation to the company and no conflicts of interest to declare.en_US
dc.identifier.doi10.1186/s10194-025-02121-0
dc.identifier.issn1129-2369
dc.identifier.issn1129-2377
dc.identifier.issue1en_US
dc.identifier.pmid40883680en_US
dc.identifier.scopus2-s2.0-105014719986en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1186/s10194-025-02121-0
dc.identifier.urihttps://hdl.handle.net/20.500.12684/21760
dc.identifier.volume26en_US
dc.identifier.wosWOS:001560320900001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherBmcen_US
dc.relation.ispartofJournal of Headacheand Painen_US
dc.relation.publicationcategoryDiğeren_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzKA_WOS_20250911
dc.subjectAnesthesiaen_US
dc.subjectCortical spreading depolarizationen_US
dc.subjectDC-coupled electrophysiologyen_US
dc.subjectFunctional ultrasounden_US
dc.subjectMigraineen_US
dc.subjectOptogeneticsen_US
dc.subjectWireless telemetryen_US
dc.titleState-of-the-art preclinical techniques to study the impact of spreading depolarizations in awake rodentsen_US
dc.typeReviewen_US

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