{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:28:40Z","timestamp":1789939720574,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold>\n<\/jats:p>\n<jats:p>Can remote liver ischaemic preconditioning (RLIPC) protect rat brain against cerebral ischaemia\u2013reperfusion injury?<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Pretreatment with RLIPC reduced cerebral infarct volume, improved neurological outcomes and inhibited neuron apoptosis. RLIPC led to increased phosphorylation of AKT, while inhibition of AKT abolished the effects of RLIPC. Our data suggest that liver ischaemic preconditioning exerts a strong neuroprotective effect against cerebral ischaemia\u2013reperfusion injury by activating an AKT\u2010dependent pathway.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Remote limb ischaemic preconditioning has been shown to have beneficial effects in protecting brains against ischaemia\u2013reperfusion (I\/R) injury. However, little is known regarding the effect of remote liver ischaemic conditioning (RLIPC). We therefore investigated the effect of RLIPC on brain tissues suffering from I\/R injury. Rats were randomly assigned to a sham group, a control group or a RLIPC group. Rats in all groups except for the sham group received middle cerebral artery occlusion (MCAO) for 1\u00a0h, followed by 48\u00a0h of reperfusion. For the RLIPC rats, four cycles of 5\u00a0min of liver ischaemia (portal vein, hepatic arterial and venous trunk occlusion) with 5\u00a0min intermittent reperfusion were carried out before cerebral ischaemia. Infarct volume was assessed after 48\u00a0h of reperfusion. Blood samples were taken for serum lactate dehydrogenase (LDH) and creatine kinase\u2010MB (CK\u2010MB) tests. Morphological changes of cortical tissue and cellular apoptosis were determined. Right cortex tissues were taken for western blotting measurements. Our data demonstrate that RLIPC reduced cerebral I\/R injury, decreased the volume of the MCAO\u2010evoked infarct region, decreased serum levels of LDH and CK\u2010MB, and reduced neurological deficits and apoptosis after I\/R injury. Moreover, rats receiving RLIPC showed increased cortical AKT phosphorylation, but protein phosphorylation level was unchanged in the survivor activating factor enhancement (SAFE) signalling pathway. Accordingly, inhibition of AKT with wortmannin abolished the neuroprotective action of liver preconditioning. Our study showed for the first time that liver ischaemic preconditioning effectively protects brain against cerebral I\/R injury by activating an AKT\u2010dependent pathway.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep088394","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T15:34:03Z","timestamp":1583422443000},"page":"852-863","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Remote liver ischaemic preconditioning protects rat brain against cerebral ischaemia\u2013reperfusion injury by activation of an AKT\u2010dependent pathway"],"prefix":"10.1113","volume":"105","author":[{"given":"Guang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Experimental Animal Center West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Lab for Aging Research Center of Gerontology and Geriatrics West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Anesthesiology &amp; Critical Care Medicine Translational Neuroscience Center West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3642-9610","authenticated-orcid":false,"given":"Zhaoyang","family":"Hu","sequence":"additional","affiliation":[{"name":"Laboratory of Anesthesiology &amp; Critical Care Medicine Translational Neuroscience Center West China Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/hs0102.101544"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.3.H1111"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70054-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(03)00238-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2018.08.116"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.022015"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-014-0284-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP085299"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007732"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2005.03.001"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.09.024"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-017-0537-3"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165123"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13957"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202810109"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1380-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.009876"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.03.019"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.20.1.84"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196186"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.009688"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.74.5.1124"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.169953"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000353125"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004666"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.87.3.893"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1074248411409040"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00054.2009"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-017-0662-x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.4.551"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1990.47"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-011-0210-z"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2007.12.747"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0444-2"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000002674"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.3000"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00862.2016"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(00)00029-3"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2018.01.036"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27858"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.11.047"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FEP088394","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP088394","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP088394","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP088394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T21:53:07Z","timestamp":1694037187000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP088394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,3]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1113\/EP088394"],"URL":"https:\/\/doi.org\/10.1113\/ep088394","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,3]]},"assertion":[{"value":"2019-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}