Remote ischemic perconditioning and postconditioning reduced cerebral ischemic injury modulating inflammatory responses and metabolic pathways

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dc.contributor.authorTorres Querol, Coral
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorArque, Gloria
dc.contributor.authorPurroy Garcia, Francisco
dc.date.accessioned2026-07-08T11:37:56Z
dc.date.available2026-07-08T11:37:56Z
dc.date.issued2026
dc.description.abstractRemote ischemic conditioning (RIC) mitigates ischemic injury through transient, repetitive vascular occlusion in a limb distant from the injury site. Although its protective effects are recognized, the underlying mechanisms remain incompletely understood. This study investigated the metabolic and inflammatory changes induced by RIC to identify novel cytoprotective targets. We used a mouse model of transient focal cerebral ischemia induced by 60-min occlusion of the distal middle cerebral artery. Two RIC protocols were applied: remote ischemic perconditioning (RIPerC), consisting of three cycles of 5-min hindlimb ischemia followed by 5-min reperfusion during ischemia, and remote ischemic postconditioning (RIPostC), applied after reperfusion. Plasma cytokines were quantified using a multiplex assay, and metabolomic profiles of plasma and brain samples were analyzed by untargeted liquid chromatography-mass spectrometry (LC-MS). Data were evaluated with univariate and multivariate statistical methods. RIC induced moderate changes in the brain metabolome but significantly increased three plasma metabolites: Cer (42:3), HexCer (36:1), and TG (28:0), suggesting systemic metabolic modulation during ischemia-reperfusion. Both RIPerC and RIPostC conferred neuroprotection, likely through regulation of peripheral immune responses. These findings demonstrate that RIPerC and RIPostC protect against ischemic injury by modulating inflammatory and metabolic pathways in systemic circulation and brain, providing insights into ischemic tolerance and biomarker discovery.
dc.identifier.doihttps://doi.org/10.1177/0271678X261458135
dc.identifier.issn1559-7016
dc.identifier.issn0271-678X
dc.identifier.urihttps://hdl.handle.net/10459.1/470827
dc.language.isoen
dc.publisherSage
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1177/0271678X261458135
dc.relation.ispartofJournal of Cerebral Blood Flow & Metabolism, 2026, p. 1– 18 [Online ahead of print]
dc.rights(c) The Authors, 2026
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.subjectBrain ischemia
dc.subjectIschemic tolerance
dc.subjectLipidomics
dc.subjectMetabolomics
dc.subjectRemote ischemic conditioning
dc.titleRemote ischemic perconditioning and postconditioning reduced cerebral ischemic injury modulating inflammatory responses and metabolic pathways
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
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