Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/106391
Title: Non-invasive multimodality imaging directly shows TRPM4 inhibition ameliorates stroke reperfusion injury
Authors: Chen, Bo
Ng, Gandi
Gao, Yahui
Low, See Wee
Sandanaraj, Edwin
Ramasamy, Boominathan
Sekar, Sakthivel
Bhakoo, Kishore
Soong, Tuck Wah
Nilius, Bernd
Tang, Carol
Robins, Edward G.
Goggi, Julian
Liao, Ping
Keywords: Stroke
Science::Biological sciences
Reperfusion
Issue Date: 2018
Source: Chen, B., Ng, G., Gao, Y., Low, S. W., Sandanaraj, E., Ramasamy, B., . . . Liao, P. (2019). Non-invasive multimodality imaging directly shows TRPM4 inhibition ameliorates stroke reperfusion injury. Translational Stroke Research, 10(1), 91-103. doi:10.1007/s12975-018-0621-3
Series/Report no.: Translational Stroke Research
Abstract: The 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.
URI: https://hdl.handle.net/10356/106391
http://hdl.handle.net/10220/49616
ISSN: 1868-4483
DOI: 10.1007/s12975-018-0621-3
Schools: School of Biological Sciences 
Rights: © 2018 The Author(s). Published by Springer US. 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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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