{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:09:29Z","timestamp":1778616569909,"version":"3.51.4"},"reference-count":34,"publisher":"BMJ","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["AES2018"],"award-info":[{"award-number":["AES2018"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["FI18\/00319"],"award-info":[{"award-number":["FI18\/00319"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Stroke Vasc Neurol"],"accepted":{"date-parts":[[2025,12,12]]},"abstract":"<jats:p>Background: Remote ischaemic conditioning (RIC) is an endogenous neuroprotective strategy involving repeated, transient occlusion of a limb artery to reduce ischaemic injury at a distant site. We investigated the effects of RIC in a mouse model of focal cerebral ischaemia induced by distal transient middle cerebral artery occlusion (tMCAO). Animals were randomised into three groups: Stroke (tMCAO, 60\u2009min), Stroke+remote ischaemic preconditioning (RIPerC) (RIC applied during ischaemia) and Stroke+remote ischaemic postconditioning (RIPostC) (RIC initiated 10\u2009min after reperfusion). The RIC protocol consisted of three cycles of 5-minute hindlimb ischaemia followed by 5-minute reperfusion.<\/jats:p>\n                  <jats:p>Results: At 72 hours postischaemia, both RIPerC and RIPostC significantly reduced the infarct volumes in male and female mice. In males, infarct size decreased from 6.31\u202f\u00b1\u202f0.28% (Stroke) to 3.77\u202f\u00b1\u202f0.47% (RIPerC, p&lt;0.0025) and 4.00\u202f\u00b1\u202f0.40% (RIPostC, p&lt;0.0061). However, the RIPerC+RIPostC group significantly increased the infarct volume compared with the Stroke group (8.41\u00b1\u202f0.72%). In females, reductions were greater: from 6.69\u00b10.46% (Stroke)\u202fto 2.95\u202f\u00b1\u202f0.34% (RIPerC, p&lt;0.0001) and 2.96\u202f\u00b1\u202f0.32% (RIPostC, p&lt;0.0001). Functional recovery was improved, particularly with RIPostC, correlating with infarct size reduction (Pearson\u2019s r=0.5505 in males, r=0.7313 in females). Apoptosis was reduced by over 50% with both treatments, and microglial phagocytic activity (cluster of differentiation 68+\/Iba1+ (ionised calcium binding adaptor molecule 1)) increased significantly.<\/jats:p>\n                  <jats:p>Microglial depletion using PLX3397 (71.3% reduction in Iba1+ cells) worsened ischaemic injury, yet RIC preserved its protective effects, suggesting additional microglia-independent mechanisms. Furthermore, RIC enhanced neurogenesis in the subventricular zone and infarct core (doublecortin marker+ cells doubled versus Stroke), with a marked proliferative response in female hippocampi (Ki67+ cells increased by 127%).<\/jats:p>\n                  <jats:p>Conclusion: These findings reveal sex-specific efficacy of RIC, with mechanistic insights obtained in male animals suggesting a dual mode of action via modulation of microglial function and promotion of endogenous neurorepair pathways.<\/jats:p>","DOI":"10.1136\/svn-2025-004465","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:40:13Z","timestamp":1767188413000},"page":"svn-2025-004465","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["RIC-specific cytoprotective profile mediated by microglia in a mouse model of acute ischaemic stroke"],"prefix":"10.1136","author":[{"given":"Coral","family":"Torres-Querol","sequence":"first","affiliation":[{"name":"Universitat de Lleida, Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Arqu\u00e9","sequence":"additional","affiliation":[{"name":"IRBLleida, Lleida, Spain"},{"name":"Psychology Department, Universitat de Lleida, Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-5968","authenticated-orcid":false,"given":"Francisco","family":"Purroy","sequence":"additional","affiliation":[{"name":"Universitat de Lleida, Lleida, Spain"},{"name":"IRBLleida, Lleida, Spain"},{"name":"Neurology, Hospital Universitari Arnau de Vilanova de Lleida, Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"2025123105400361000_svn-2025-004465v1.1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1177\/2396987319883160","article-title":"Economic burden of stroke across Europe: A population-based cost analysis","volume":"5","author":"Luengo-Fernandez","year":"2020","journal-title":"Eur Stroke J"},{"key":"2025123105400361000_svn-2025-004465v1.2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.33588\/rn.7309.2021138","article-title":"Epidemiology of stroke in the last decade: a systematic review","volume":"73","author":"Purroy","year":"2021","journal-title":"Rev 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