Sistema de Salut de Catalunya
Institut Català de la Salut
[Loppi S] A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Department of Immunobiology, University of Arizona, Tucson, Arizona, USA. [Korhonen P, Turunen TA, Turunen MP] A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. [Bouvy-Liivrand M] School of Medicine, University of Eastern Finland, Kuopio, Finland. [Caligola S] Department of Computer Science, University of Verona, Verona, Italy. [Rosell A, García-Berrocoso T, Montaner J] Laboratori de Malalties Neurovasculars, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
2021-05-14T12:13:22Z
2021-05-14T12:13:22Z
2021-01
Envelliment; Inflamació; MicroARN
Envejecimiento; Inflamación; MicroARN
Aging; Inflammation; MicroRNA
Ischemic stroke, the third leading cause of death in the Western world, affects mainly the elderly and is strongly associated with comorbid conditions such as atherosclerosis or diabetes, which are pathologically characterized by increased inflammation and are known to influence the outcome of stroke. Stroke incidence peaks during influenza seasons, and patients suffering from infections such as pneumonia prior to stroke exhibit a worse stroke outcome. Earlier studies have shown that comorbidities aggravate the outcome of stroke, yet the mediators of this phenomenon remain obscure. Here, we show that acute peripheral inflammation aggravates stroke‐induced neuronal damage and motor deficits specifically in aged mice. This is associated with increased levels of plasma proinflammatory cytokines, rather than with an increase of inflammatory mediators in the affected brain parenchyma. Nascent transcriptomics data with mature microRNA sequencing were used to identify the neuron‐specific miRNome, in order to decipher dysregulated miRNAs in the brains of aged animals with stroke and co‐existing inflammation. We pinpoint a previously uninvestigated miRNA in the brain, miR‐127, that is highly neuronal, to be associated with increased cell death in the aged, LPS‐injected ischemic mice. Target prediction tools indicate that miR‐127 interacts with several basally expressed neuronal genes, and of these we verify miR‐127 binding to Psmd3. Finally, we report reduced expression of miR‐127 in human stroke brains. Our results underline the impact of peripheral inflammation on the outcome of stroke in aged subjects and pinpoint molecular targets for restoring endogenous neuronal capacity to combat ischemic stroke.
This study was supported by Emil Aaltonen Foundation, Academy of Finland and Finnish Cultural Foundation.
Article
Published version
English
Isquèmia cerebral; Animals; DISEASES::Cardiovascular Diseases::Vascular Diseases::Cerebrovascular Disorders::Stroke; DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Brain Ischemia; ORGANISMS::Eukaryota::Animals; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::accidente cerebrovascular; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::isquemia cerebral; ORGANISMOS::Eukaryota::animales
Wiley
Aging Cell;20(1)
https://doi.org/10.1111/acel.13287
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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