Publication:
The effect of P2X7 antagonism on subcortical spread of optogenetically-triggered cortical spreading depression and neuroinflammation

dc.contributor.coauthorUzay, Burak
dc.contributor.coauthorDonmez-Demir, Buket
dc.contributor.coauthorOzcan, Sinem Yilmaz
dc.contributor.coauthorKocak, Emine Eren
dc.contributor.coauthorYemisci, Muge
dc.contributor.coauthorDalkara, Turgay
dc.contributor.coauthorKaratas, Hulya
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorÖzdemir, Yasemin Gürsoy
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-12-29T09:38:30Z
dc.date.issued2024
dc.description.abstractMigraine is a neurological disorder characterized by episodes of severe headache. Cortical spreading depression (CSD), the electrophysiological equivalent of migraine aura, results in opening of pannexin 1 megachannels that release ATP and triggers parenchymal neuroinflammatory signaling cascade in the cortex. Migraine symptoms suggesting subcortical dysfunction bring subcortical spread of CSD under the light. Here, we investigated the role of purinergic P2X7 receptors on the subcortical spread of CSD and its consequent neuroinflammation using a potent and selective P2X7R antagonist, JNJ-47965567. P2X7R antagonism had no effect on the CSD threshold and characteristics but increased the latency to hypothalamic voltage deflection following CSD suggesting that ATP acts as a mediator in the subcortical spread. P2X7R antagonism also prevented cortical and subcortical neuronal activation following CSD, revealed by bilateral decrease in c-fos positive neuron count, and halted CSD-induced neuroinflammation revealed by decreased neuronal HMGB1 release and decreased nuclear translocation of NF-kappa B-p65 in astrocytes. In conclusion, our data suggest that P2X7R plays a role in CSD-induced neuroinflammation, subcortical spread of CSD and CSD-induced neuronal activation hence can be a potential target.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue1
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipWe thank Mesut F & imath;rat for his expert help with technical issues and Beyza Turken, MD, PhD candidate for the help of electrophysiological analysis. The authors declare no competing financial interests. Graphical depictions were prepared at Biorender.com.
dc.description.volume25
dc.identifier.doi10.1186/s10194-024-01807-1
dc.identifier.eissn1129-2377
dc.identifier.issn1129-2369
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85199265069
dc.identifier.urihttps://doi.org/10.1186/s10194-024-01807-1
dc.identifier.urihttps://hdl.handle.net/20.500.14288/22687
dc.identifier.wos1274898000001
dc.keywordsMigraine
dc.keywordsCSD
dc.keywordsSubcortical spread
dc.keywordsNeuroinflammation
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofJournal of Headache and Pain
dc.subjectClinical neurology
dc.subjectNeurosciences
dc.titleThe effect of P2X7 antagonism on subcortical spread of optogenetically-triggered cortical spreading depression and neuroinflammation
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorÖzdemir, Yasemin Gürsoy
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit2School of Medicine
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