Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.11851/8966
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dc.contributor.authorHanalioglu, Sahin-
dc.contributor.authorTaskiran-Sag, Aslihan-
dc.contributor.authorKaratas, Hulya-
dc.contributor.authorDonmez-Demir, Buket-
dc.contributor.authorYilmaz-Ozcan, Sinem-
dc.contributor.authorEren-Kocak, Emine-
dc.contributor.authorDalkara, Turgay-
dc.date.accessioned2022-11-30T19:24:52Z-
dc.date.available2022-11-30T19:24:52Z-
dc.date.issued2022-
dc.identifier.issn1129-2369-
dc.identifier.issn1129-2377-
dc.identifier.urihttps://doi.org/10.1186/s10194-022-01474-0-
dc.identifier.urihttps://hdl.handle.net/20.500.11851/8966-
dc.description.abstractBackground Unlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain. Methods Cortex was made susceptible to CSD with partial inhibition of Na+/K+-ATPase by epidural application of a low concentration of Na+/K+-ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down alpha 2 subunit of Na+/K+-ATPase, which is crucial for K+ and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K+ changes were monitored in vivo electrophysiologically and a K+-sensitive fluoroprobe (IPG-4), respectively. Results After priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p < 0.001). Whisker stimulation also significantly increased the CSD incidence, albeit less effectively (14.9 vs. 2.4%, p = 0.02). Knocking-down Na+/K+-ATPase (50% decrease in mRNA) lowered the CSD threshold in all mice tested with KCl but triggered CSDs in 14.3% and 16.7% of mice with photic and whisker stimulation, respectively. Confirming Na+/K+-ATPase hypofunction, extracellular K+ significantly rose during sensory stimulation after ouabain or shRNA treatment unlike controls. In line with the higher CSD susceptibility observed, K+ rise was more prominent after ouabain. To gain insight to preventive mechanisms reducing the probability of stimulus-evoked CSDs, we applied an A1-receptor antagonist (DPCPX) to the occipital cortex, because adenosine formed during stimulation from ATP can reduce CSD susceptibility. DPCPX induced spontaneous CSDs but only small-DC shifts along with suppression of EEG spikes during photic stimulation, suggesting that the inhibition co-activated with sensory stimulation could limit CSD ignition when K+ uptake was not sufficiently suppressed as with ouabain. Conclusions Normal brain is well protected against CSD generation. For CSD to be ignited under physiological conditions, priming and predisposing factors are required as seen in migraine patients. Intense sensory stimulation has potential to trigger CSD when co-existing conditions bring extracellular K+ and glutamate concentrations over CSD-ignition threshold and stimulation-evoked inhibitory mechanisms are overcome.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey [TUBITAK-113S211]; Hacettepe University Scientific Research Projects Unit [014-D01-105-002]en_US
dc.description.sponsorshipThis study was supported by grants from The Scientific and Technological Research Council of Turkey (TUBITAK-113S211) and Hacettepe University Scientific Research Projects Unit (014-D01-105-002).en_US
dc.language.isoenen_US
dc.publisherBmcen_US
dc.relation.ispartofJournal of Headache and Painen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCortical spreading depressionen_US
dc.subjectOuabainen_US
dc.subjectAsante Potassium Green-4en_US
dc.subjectPhotic stimulationen_US
dc.subjectWhisker stimulationen_US
dc.subjectMigraineen_US
dc.subjectGlutamate Transportersen_US
dc.subjectAlpha-2 Subuniten_US
dc.subjectSusceptibilityen_US
dc.subjectAstrocytesen_US
dc.subjectInductionen_US
dc.subjectIncreasesen_US
dc.subjectImpacten_US
dc.subjectAtpaseen_US
dc.subjectCortexen_US
dc.subjectPumpen_US
dc.titleCortical Spreading Depression Can Be Triggered by Sensory Stimulation in Primed Wild Type Mouse Brain: a Mechanistic Insight To Migraine Aura Generationen_US
dc.typeArticleen_US
dc.identifier.volume23en_US
dc.identifier.issue1en_US
dc.identifier.wosWOS:000842037300001en_US
dc.identifier.scopus2-s2.0-85136937965en_US
dc.institutionauthorTaskiran Sag, Aslihan-
dc.identifier.pmid35986251en_US
dc.identifier.doi10.1186/s10194-022-01474-0-
dc.authorscopusid55801129800-
dc.authorscopusid55982279000-
dc.authorscopusid57223396104-
dc.authorscopusid56429617800-
dc.authorscopusid56364900300-
dc.authorscopusid25922160600-
dc.authorscopusid6602957844-
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.scopusqualityQ1-
dc.ozel2022v3_Editen_US
item.openairetypeArticle-
item.languageiso639-1en-
item.grantfulltextnone-
item.fulltextNo Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
Appears in Collections:Dahili Tıp Bilimleri Bölümü / Department of Internal Medical Sciences
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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