Expression of miR-200c corresponds with increased reactive oxygen species and hypoxia markers after transient focal ischemia in mice.


Journal

Neurochemistry international
ISSN: 1872-9754
Titre abrégé: Neurochem Int
Pays: England
ID NLM: 8006959

Informations de publication

Date de publication:
10 2021
Historique:
received: 19 02 2021
revised: 24 07 2021
accepted: 26 07 2021
pubmed: 4 8 2021
medline: 5 2 2022
entrez: 3 8 2021
Statut: ppublish

Résumé

Embolic stroke results in a necrotic core of cells destined to die, but also a peri-ischemic, watershed penumbral region of potentially salvageable brain tissue. Approaches to effectively differentiate between the ischemic and peri-ischemic zones is critical for novel therapeutic discovery to improve outcomes in survivors of stroke. MicroRNAs are a class of small non-coding RNAs regulating gene translation that have region- and cell-specific expression and responses to ischemia. We have previously reported that global inhibition of cerebral microRNA-200c after experimental stroke in mice is protective, however delineating the post-stroke sub-regional and cell-type specific patterns of post-stroke miR-200c expression are necessary to minimize off-target effects and advance translational application. Here, we detail a novel protocol to visualize regional miR-200c expression after experimental stroke, complexed with visualization of regional ischemia and markers of oxidative stress in an experimental stroke model in mice. In the present study we demonstrate that the fluorescent hypoxia indicator pimonidazole hydrochloride, the reactive-oxygen-species marker 8-hydroxy-deoxyguanosine, neuronal marker MAP2 and NeuN, and the reactive astrocyte marker GFAP can be effectively complexed to determine regional differences in ischemic injury as early as 30 min post-reperfusion after experimental stroke, and can be effectively used to distinguish ischemic core from surrounding penumbral and unaffected regions for targeted therapy. This multi-dimensional post-stroke immunofluorescent imaging protocol enables a greater degree of sub-regional mechanistic investigation, with the ultimate goal of developing more effective post-stroke pharmaceutical therapy.

Identifiants

pubmed: 34343653
pii: S0197-0186(21)00192-3
doi: 10.1016/j.neuint.2021.105146
pmc: PMC8387456
mid: NIHMS1731166
pii:
doi:

Substances chimiques

MicroRNAs 0
Mirn200 microRNA, mouse 0
Reactive Oxygen Species 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

105146

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS107445
Pays : United States

Informations de copyright

Copyright © 2021. Published by Elsevier Ltd.

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Auteurs

Oiva Arvola (O)

Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; Division of Anaesthesiology, Jorvi Hospital, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Stem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Brian Griffiths (B)

Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Anand Rao (A)

Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Lijun Xu (L)

Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Iason-Alexander Pastroudis (IA)

Department of Anesthetics, Pain Medicine and Intensive Care, Imperial College London, UK.

Creed M Stary (CM)

Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: cstary@stanford.edu.

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Classifications MeSH