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NADPH oxidase inhibitor regulates microRNAs with improved outcome after mechanical reperfusion
- Source :
- Journal of NeuroInterventional Surgery. 9:702-706
- Publication Year :
- 2016
- Publisher :
- BMJ, 2016.
-
Abstract
- BackgroundInhibition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) pathway improves the neurological outcome in the transient middle cerebral artery occlusion (tMCAO) animal model. In this study we analyzed the microRNAs profile targeting NOX2 and NOX4 genes and its response to NOX2/4 inhibitor VAS2870 to understand the mechanisms of this protective effect.MethodsThe intraluminal filament tMCAO model was established in hyperglycemic rats (n=106) with 5 hours ischemia followed by 19 hours reperfusion. NOX inhibitor VAS2870 was delivered intravenously before reperfusion. Infarct volume, hemorrhagic transformation, and mortality were determined at 24 hours after cerebral ischemia. MicroRNAs profile targeting NOX2 and NOX4 genes were predicted by microRNA databases and further evaluated by microRNA microarray and quantitative RT-PCR.ResultsTen microRNAs potentially targeting NOX2 and NOX4 genes (including microRNA-29a, microRNA-29c, microRNA-126a, microRNA-132, microRNA-136, microRNA-138, microRNA-139, microRNA-153, microRNA-337, and microRNA-376a) were significantly downregulated in the ischemic hemisphere in the tMCAO group compared with the sham-operated group, as shown by microRNA microarray and quantitative RT-PCR (all pConclusionsSeveral microRNAs potentially targeting NOX2 and NOX4 genes displayed altered levels in hyperglycemic rats with the tMCAO model, suggesting their regulatory roles and targeting potentials for acute ischemic stroke treatment. Targeting specific microRNAs may represent a novel intervention opportunity to improve outcome and reduce hemorrhagic transformation after mechanical reperfusion for acute ischemic stroke.
- Subjects :
- Male
0301 basic medicine
Pathology
medicine.medical_specialty
Basic science
Ischemia
Pharmacology
Brain Ischemia
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
microRNA
medicine
Animals
Stroke
Benzoxazoles
Oxidase test
NADPH oxidase
biology
business.industry
NADPH Oxidases
NOX4
Infarction, Middle Cerebral Artery
General Medicine
Triazoles
medicine.disease
Rats
MicroRNAs
Treatment Outcome
030104 developmental biology
chemistry
Reperfusion
cardiovascular system
biology.protein
Surgery
Neurology (clinical)
business
030217 neurology & neurosurgery
Nicotinamide adenine dinucleotide phosphate
Subjects
Details
- ISSN :
- 17598486 and 17598478
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of NeuroInterventional Surgery
- Accession number :
- edsair.doi.dedup.....387678930dba3257321c268e19e15889