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dc.contributor.authorChen, Bo
dc.contributor.authorNg, Gandi
dc.contributor.authorGao, Yahui
dc.contributor.authorLow, See Wee
dc.contributor.authorSandanaraj, Edwin
dc.contributor.authorRamasamy, Boominathan
dc.contributor.authorSekar, Sakthivel
dc.contributor.authorBhakoo, Kishore
dc.contributor.authorSoong, Tuck Wah
dc.contributor.authorNilius, Bernd
dc.contributor.authorTang, Carol
dc.contributor.authorRobins, Edward G
dc.contributor.authorGoggi, Julian
dc.contributor.authorLiao, Ping
dc.date.accessioned2020-01-17T01:50:51Z
dc.date.available2020-01-17T01:50:51Z
dc.date.issued2019
dc.identifier.issn1868-4483
dc.identifier.doi10.1007/s12975-018-0621-3
dc.identifier.urihttp://hdl.handle.net/10072/390575
dc.description.abstractThe transient receptor potential melastatin 4 (TRPM4) channel has been suggested to play a key role in the treatment of ischemic stroke. However, in vivo evaluation of TRPM4 channel, in particular by direct channel suppression, is lacking. In this study, we used multimodal imaging to assess edema formation and quantify the amount of metabolically functional brain salvaged after a rat model of stroke reperfusion. TRPM4 upregulation in endothelium emerges as early as 2 h post-stroke induction. Expression of TRPM4 channel was suppressed directly in vivo by treatment with siRNA; scrambled siRNA was used as a control. T2-weighted MRI suggests that TRPM4 inhibition successfully reduces edema by 30% and concomitantly salvages functionally active brain, measured by 18F-FDG-PET. These in vivo imaging results correlate well with post-mortem 2,3,5-triphenyltetrazolium chloride (TTC) staining which exhibits a 34.9% reduction in infarct volume after siRNA treatment. Furthermore, in a permanent stroke model, large areas of brain tissue displayed both edema and significant reductions in metabolic activity which was not shown in transient models with or without TRPM4 inhibition, indicating that tissue salvaged by TRPM4 inhibition during stroke reperfusion may survive. Evans Blue extravasation and hemoglobin quantification in the ipsilateral hemisphere were greatly reduced, suggesting that TRPM4 inhibition can improve BBB integrity after ischemic stroke reperfusion. Our results support the use of TRPM4 blocker for early stroke reperfusion.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofpagefrom91
dc.relation.ispartofpageto103
dc.relation.ispartofissue1
dc.relation.ispartofjournalTranslational Stroke Research
dc.relation.ispartofvolume10
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchPublic Health and Health Services
dc.subject.fieldofresearchcode1103
dc.subject.fieldofresearchcode1109
dc.subject.fieldofresearchcode1117
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsClinical Neurology
dc.subject.keywordsNeurosciences & Neurology
dc.titleNon-Invasive Multimodality Imaging Directly Shows TRPM4 Inhibition Ameliorates Stroke Reperfusion Injury
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationChen, B; Ng, G; Gao, Y; Low, SW; Sandanaraj, E; Ramasamy, B; Sekar, S; Bhakoo, K; Soong, TW; Nilius, B; Tang, C; Robins, EG; Goggi, J; Liao, P, Non-Invasive Multimodality Imaging Directly Shows TRPM4 Inhibition Ameliorates Stroke Reperfusion Injury, Translational Stroke Research, 2019, 10 (1), pp. 91-103
dcterms.dateAccepted2018-03-08
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-01-17T01:47:09Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
gro.hasfulltextFull Text
gro.griffith.authorNilius, Bernd


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