Please use this identifier to cite or link to this item: https://doi.org/10.1007/s12975-018-0621-3
Title: Non-Invasive Multimodality Imaging Directly Shows TRPM4 Inhibition Ameliorates Stroke Reperfusion Injury
Authors: Chen B. 
Ng G.
Gao Y.
Low S.W.
Sandanaraj E.
Ramasamy B.
Sekar S.
Bhakoo K. 
Soong T.W. 
Nilius B.
Tang C. 
Robins E.G.
Goggi J. 
Liao P. 
Keywords: claudin 1
claudin 2
Evans blue
hemoglobin
small interfering RNA
transient receptor potential channel M4
von Willebrand factor
enolase
fluorodeoxyglucose f 18
messenger RNA
small interfering RNA
transient receptor potential channel M
TRPM4 protein, rat
animal experiment
animal model
animal tissue
Article
blood brain barrier
brain capillary endothelial cell
brain edema
brain infarction
brain protection
brain tissue
cell survival
cerebrovascular accident
controlled study
extravasation
hemisphere
human
human cell
in vitro study
in vivo study
infarct volume
magnetic field
male
middle cerebral artery occlusion
motor performance
multimodal imaging
nerve cell growth
neuroimaging
non invasive procedure
nonhuman
nuclear magnetic resonance imaging
positron emission tomography
priority journal
protein expression
rat
reperfusion injury
stroke patient
animal
antagonists and inhibitors
blood brain barrier
brain edema
cerebral artery disease
complication
disease model
gene expression regulation
genetics
hemispheric dominance
image processing
metabolism
microarray analysis
multimodal imaging
pathology
pathophysiology
physiology
procedures
reperfusion injury
Wistar rat
Animals
Blood-Brain Barrier
Brain Edema
Disease Models, Animal
Fluorodeoxyglucose F18
Functional Laterality
Gene Expression Regulation
Image Processing, Computer-Assisted
Infarction, Middle Cerebral Artery
Male
Microarray Analysis
Multimodal Imaging
Phosphopyruvate Hydratase
Rats
Rats, Wistar
Reperfusion Injury
RNA, Messenger
RNA, Small Interfering
TRPM Cation Channels
von Willebrand Factor
Issue Date: 2019
Publisher: Springer
Citation: Chen B., Ng G., Gao Y., Low S.W., Sandanaraj E., Ramasamy B., Sekar S., Bhakoo K., Soong T.W., Nilius B., Tang C., Robins E.G., Goggi J., Liao P. (2019). Non-Invasive Multimodality Imaging Directly Shows TRPM4 Inhibition Ameliorates Stroke Reperfusion Injury. Translational Stroke Research 10 (1) : 91-103. ScholarBank@NUS Repository. https://doi.org/10.1007/s12975-018-0621-3
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 18 F-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. © 2018, The Author(s).
Source Title: Translational Stroke Research
URI: https://scholarbank.nus.edu.sg/handle/10635/174510
ISSN: 18684483
DOI: 10.1007/s12975-018-0621-3
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