Journal article
miR-98 reduces endothelial dysfunction by protecting blood-brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model
Journal of cerebral blood flow and metabolism, v 40(10), pp 1953-1965
01 Oct 2020
PMID: 31601141
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Most neurological diseases, including stroke, lead to some degree of blood-brain barrier (BBB) dysfunction. A significant portion of BBB injury is caused by inflammation, due to pro-inflammatory factors produced in the brain, and by leukocyte engagement of the brain endothelium. Recently, microRNAs (miRNAs) have appeared as major regulators of inflammation-induced changes to gene expression in the microvascular endothelial cells (BMVEC) that comprise the BBB. However, miRNAs' role during cerebral ischemia/reperfusion is still underexplored. Endothelial levels of miR-98 were significantly altered following ischemia/reperfusion insults, both in vivo and in vitro, transient middle cerebral artery occlusion (tMCAO), and oxygen-glucose deprivation (OGD), respectively. Overexpression of miR-98 reduced the mouse's infarct size after tMCAO. Further, miR-98 lessened infiltration of proinflammatory Ly6C(HI) leukocytes into the brain following stroke and diminished the prevalence of M1 (activated) microglia within the impacted area. miR-98 attenuated BBB permeability, as demonstrated by changes to fluorescently-labeled dextran penetration in vivo and improved transendothelial electrical resistance (TEER) in vitro. Treatment with miR-98 improved significantly the locomotor impairment. Our study provides identification and functional assessment of miRNAs in brain endothelium and lays the groundwork for improving therapeutic approaches for patients suffering from ischemic attacks.
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Details
- Title
- miR-98 reduces endothelial dysfunction by protecting blood-brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model
- Creators
- David L. Bernstein - Temple UniversityViviana Zuluaga-Ramirez - Temple UniversitySachin Gajghate - Temple UniversityNancy L. Reichenbach - Temple UniversityBoris Polyak - Drexel UniversityYuri Persidsky - Temple UniversitySlava Rom - Temple University
- Publication Details
- Journal of cerebral blood flow and metabolism, v 40(10), pp 1953-1965
- Publisher
- Sage
- Number of pages
- 13
- Grant note
- R01NS101135; R01AA015913; R01MH115786 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R37AA015913 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) R01MH115786 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01NS101135 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Web of Science ID
- WOS:000491525300001
- Scopus ID
- 2-s2.0-85074085390
- Other Identifier
- 991019168029804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism
- Hematology
- Neurosciences