{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:48:06Z","timestamp":1790758086631,"version":"4.1.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T00:00:00Z","timestamp":1576886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T00:00:00Z","timestamp":1576886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008880","name":"Kohn Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008880","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edward Bonham Carter Doctoral Scholarship","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"EPSRC\/MRC","award":["EP\/L014904\/1"],"award-info":[{"award-number":["EP\/L014904\/1"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K501311\/1"],"award-info":[{"award-number":["MR\/K501311\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl. Stroke Res."],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During recovery, stroke patients are at risk of developing long-term complications that impact quality of life, including changes in body weight and composition, depression and anxiety, as well as an increased risk of subsequent vascular events. The aetiologies and time-course of these post-stroke complications have not been extensively studied and are poorly understood. Therefore, we assessed long-term changes in body composition, metabolic markers and behaviour after middle cerebral artery occlusion in mice. These outcomes were also studied in the context of obesity, a common stroke co-morbidity proposed to protect against post-stroke weight loss in patients. We found that stroke induced long-term changes in body composition, characterised by a sustained loss of fat mass with a recovery of lean weight loss. These global changes in response to stroke were accompanied by an altered lipid profile (increased plasma free fatty acids and triglycerides) and increased adipokine release at 60\u00a0days. After stroke, the liver also showed histological changes indicative of liver damage and a decrease in plasma alanine aminotransferase (ALT) was observed. Stroke induced depression and anxiety-like behaviours in mice, illustrated by deficits in exploration, nest building and burrowing behaviours. When initial infarct volumes were matched between mice with and without comorbid obesity, these outcomes were not drastically altered. Overall, we found that stroke induced long-term changes in depressive\/anxiety-like behaviours, and changes in plasma lipids, adipokines and the liver that may impact negatively on future vascular health.<\/jats:p>","DOI":"10.1007\/s12975-019-00763-2","type":"journal-article","created":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T14:02:20Z","timestamp":1576936940000},"page":"837-850","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice"],"prefix":"10.1007","volume":"11","author":[{"given":"Michael J.","family":"Haley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire S.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"O\u2019Toole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona J.","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Rivers-Auty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"O\u2019Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Lane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Heaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M.","family":"Allan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2372-2968","authenticated-orcid":false,"given":"Catherine B.","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,21]]},"reference":[{"key":"763_CR1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000478851","volume":"7","author":"AE Nakling","year":"2017","unstructured":"Nakling AE, Aarsland D, N\u00e6ss H, Wollschlaeger D, Fladby T, Hofstad H, et al. Cognitive deficits in chronic stroke patients: neuropsychological assessment, depression, and self-reports. Dement Geriatr Cogn Dis Extra. 2017;7:283\u201396.","journal-title":"Dement Geriatr Cogn Dis Extra"},{"key":"763_CR2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1136\/svn-2017-000123","volume":"3","author":"K Shi","year":"2018","unstructured":"Shi K, Wood K, Shi F-D, Wang X, Liu Q. Stroke-induced immunosuppression and poststroke infection. Stroke Vasc Neurol. 2018;3:34\u201341.","journal-title":"Stroke Vasc Neurol"},{"key":"763_CR3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jpsychores.2012.04.001","volume":"73","author":"F Duncan","year":"2012","unstructured":"Duncan F, Wu S, Mead GE. Frequency and natural history of fatigue after stroke: a systematic review of longitudinal studies. J Psychosom Res. 2012;73:18\u201327.","journal-title":"J Psychosom Res"},{"key":"763_CR4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1192\/bjp.bp.111.107664","volume":"202","author":"L Ayerbe","year":"2013","unstructured":"Ayerbe L, Ayis S, Wolfe CDA, Rudd AG. Natural history, predictors and outcomes of depression after stroke: systematic review and meta-analysis. Br J Psychiatry. 2013;202:14\u201321.","journal-title":"Br J Psychiatry"},{"key":"763_CR5","doi-asserted-by":"crossref","first-page":"e695","DOI":"10.1212\/WNL.0000000000007935","volume":"93","author":"M Boulanger","year":"2019","unstructured":"Boulanger M, Li L, Lyons S, Lovett NG, Kubiak MM, Silver L, et al. Effect of coexisting vascular disease on long-term risk of recurrent events after TIA or stroke. Neurology. 2019;93:e695\u2013707.","journal-title":"Neurology."},{"key":"763_CR6","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/ana.22091","volume":"68","author":"J Putaala","year":"2010","unstructured":"Putaala J, Haapaniemi E, Metso AJ, Metso TM, Artto V, Kaste M, et al. Recurrent ischemic events in young adults after first-ever ischemic stroke. Ann Neurol. 2010;68:661\u201371.","journal-title":"Ann Neurol"},{"key":"763_CR7","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/jcsm.12400","volume":"10","author":"N Scherbakov","year":"2019","unstructured":"Scherbakov N, Pietrock C, Sandek A, Ebner N, Valentova M, Springer J, et al. Body weight changes and incidence of cachexia after stroke. J Cachexia Sarcopenia Muscle. 2019;10:611\u201320.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"763_CR8","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1161\/STROKEAHA.107.497602","volume":"39","author":"A-C J\u00f6nsson","year":"2008","unstructured":"J\u00f6nsson A-C, Lindgren I, Norrving B, Lindgren A. Weight loss after stroke: a population-based study from the Lund Stroke Register. Stroke. 2008;39:918\u201323.","journal-title":"Stroke."},{"issue":"Suppl A100","key":"763_CR9","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/ijs.12554","volume":"10","author":"Y Kim","year":"2015","unstructured":"Kim Y, Kim CK, Jung S, Ko S-B, Lee S-H, Yoon B-W. Prognostic importance of weight change on short-term functional outcome in acute ischemic stroke. Int J Stroke. 2015;10(Suppl A100):62\u20138.","journal-title":"Int J Stroke"},{"key":"763_CR10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jstrokecerebrovasdis.2015.08.033","volume":"25","author":"M Nii","year":"2016","unstructured":"Nii M, Maeda K, Wakabayashi H, Nishioka S, Tanaka A. Nutritional improvement and energy intake are associated with functional recovery in patients after cerebrovascular disorders. J Stroke Cerebrovasc Dis. 2016;25:57\u201362.","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"763_CR11","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.04.012","volume":"28","author":"M Sato","year":"2019","unstructured":"Sato M, Ido Y, Yoshimura Y, Mutai H. Relationship of malnutrition during hospitalization with functional recovery and postdischarge destination in elderly stroke patients. J Stroke Cerebrovasc Dis. 2019;28:1866\u201372.","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"763_CR12","doi-asserted-by":"crossref","unstructured":"Desai R, Amraotkar AR. Letter to the editor regarding \u201crelationship of malnutrition during hospitalization with functional recovery and postdischarge destination in elderly stroke patients\u201d. J Stroke Cerebrovasc Dis 2019;104347.","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104347"},{"key":"763_CR13","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.jstrokecerebrovasdis.2015.12.017","volume":"25","author":"F Gomes","year":"2016","unstructured":"Gomes F, Emery PW, Weekes CE. Risk of malnutrition is an independent predictor of mortality, length of hospital stay, and hospitalization costs in stroke patients. J Stroke Cerebrovasc Dis. 2016;25:799\u2013806.","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"763_CR14","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/eurheartj\/ehs340","volume":"34","author":"W Doehner","year":"2013","unstructured":"Doehner W, Schenkel J, Anker SD, Springer J, Audebert HJ. Overweight and obesity are associated with improved survival, functional outcome, and stroke recurrence after acute stroke or transient ischaemic attack: observations from the TEMPiS trial. Eur Heart J. 2013;34:268\u201377.","journal-title":"Eur Heart J"},{"key":"763_CR15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/ijs.12016","volume":"10","author":"KK Andersen","year":"2015","unstructured":"Andersen KK, Olsen TS. The obesity paradox in stroke: lower mortality and lower risk of readmission for recurrent stroke in obese stroke patients. Int J Stroke. 2015;10:99\u2013104.","journal-title":"Int J Stroke"},{"key":"763_CR16","doi-asserted-by":"crossref","first-page":"e0123516","DOI":"10.1371\/journal.pone.0123516","volume":"10","author":"H-J Wang","year":"2015","unstructured":"Wang H-J, Si Q-J, Shan Z-L, Guo Y-T, Lin K, Zhao X-N, et al. Effects of body mass index on risks for ischemic stroke, thromboembolism, and mortality in Chinese atrial fibrillation patients: a single-center experience. Folli F. PLoS One. 2015;10:e0123516.","journal-title":"PLoS One"},{"key":"763_CR17","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000118945","volume":"30","author":"TS Olsen","year":"2008","unstructured":"Olsen TS, Dehlendorff C, Petersen HG, Andersen KK. Body mass index and poststroke mortality. Neuroepidemiology. 2008;30:93\u2013100.","journal-title":"Neuroepidemiology."},{"key":"763_CR18","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1242\/dmm.030411","volume":"10","author":"MJ Haley","year":"2017","unstructured":"Haley MJ, Mullard G, Hollywood KA, Cooper GJ, Dunn WB, Lawrence CB. Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice. Dis Model Mech. 2017;10:1229\u201343.","journal-title":"Dis Model Mech"},{"key":"763_CR19","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1515\/revneuro-2016-0055","volume":"28","author":"J Gairolla","year":"2017","unstructured":"Gairolla J, Kler R, Modi M, Khurana D. Leptin and adiponectin: pathophysiological role and possible therapeutic target of inflammation in ischemic stroke. Rev Neurosci. 2017;28:295\u2013306.","journal-title":"Rev Neurosci"},{"key":"763_CR20","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.biopha.2017.12.074","volume":"98","author":"R Opatrilova","year":"2018","unstructured":"Opatrilova R, Caprnda M, Kubatka P, Valentova V, Uramova S, Nosal V, et al. Adipokines in neurovascular diseases. Biomed Pharmacother. 2018;98:424\u201332.","journal-title":"Biomed Pharmacother"},{"key":"763_CR21","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2340\/16501977-0269","volume":"40","author":"AG Karatepe","year":"2008","unstructured":"Karatepe AG, Gunaydin R, Kaya T, Turkmen G. Comorbidity in patients after stroke: impact on functional outcome. J Rehabil Med. 2008;40:831\u20135.","journal-title":"J Rehabil Med"},{"key":"763_CR22","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0140-6736(10)60834-3","volume":"376","author":"MJ O'Donnell","year":"2010","unstructured":"O'Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376:112\u201323.","journal-title":"Lancet."},{"key":"763_CR23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/j.2048-7940.2006.tb00004.x","volume":"31","author":"SK Ostwald","year":"2006","unstructured":"Ostwald SK, Wasserman J, Davis S. Medications, comorbidities, and medical complications in stroke survivors: the CAReS study. Rehabil Nurs. 2006;31:10\u20134.","journal-title":"Rehabil Nurs"},{"key":"763_CR24","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.4103\/1673-5374.165208","volume":"10","author":"RE Sandu","year":"2015","unstructured":"Sandu RE, Buga A-M, Uzoni A, Petcu EB, Popa-Wagner A. Neuroinflammation and comorbidities are frequently ignored factors in CNS pathology. Neural Regen Res. 2015;10:1349\u201355.","journal-title":"Neural Regen Res"},{"key":"763_CR25","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12974-015-0359-8","volume":"12","author":"S Maysami","year":"2015","unstructured":"Maysami S, Haley MJ, Gorenkova N, Krishnan S, McColl BW, Lawrence CB. Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke. J Neuroinflammation. 2015;12:140.","journal-title":"J Neuroinflammation"},{"key":"763_CR26","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1177\/0271678X16629976","volume":"37","author":"MJ Haley","year":"2017","unstructured":"Haley MJ, Lawrence CB. The blood-brain barrier after stroke: structural studies and the role of transcytotic vesicles. J Cereb Blood Flow Metab. 2017;37:456\u201370.","journal-title":"J Cereb Blood Flow Metab"},{"key":"763_CR27","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/jcbfm.2009.217","volume":"30","author":"BW McColl","year":"2010","unstructured":"McColl BW, Rose N, Robson FH, Rothwell NJ, Lawrence CB. Increased brain microvascular MMP-9 and incidence of haemorrhagic transformation in obese mice after experimental stroke. J Cereb Blood Flow Metab. 2010;30:267\u201372.","journal-title":"J Cereb Blood Flow Metab"},{"key":"763_CR28","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1177\/0271678X16670411","volume":"36","author":"MJ Haley","year":"2016","unstructured":"Haley MJ, Lawrence CB. Obesity and stroke: can we translate from rodents to patients? J Cereb Blood Flow Metab. 2016;36:2007\u201321.","journal-title":"J Cereb Blood Flow Metab"},{"key":"763_CR29","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1161\/STROKEAHA.110.593434","volume":"42","author":"K Vemmos","year":"2011","unstructured":"Vemmos K, Ntaios G, Spengos K, Savvari P, Vemmou A, Pappa T, et al. Association between obesity and mortality after acute first-ever stroke: the obesity-stroke paradox. Stroke. 2011;42:30\u20136.","journal-title":"Stroke."},{"key":"763_CR30","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.1161\/STROKEAHA.111.619163","volume":"42","author":"N Scherbakov","year":"2011","unstructured":"Scherbakov N, Dirnagl U, Doehner W. Body weight after stroke: lessons from the obesity paradox. Stroke. 2011;42:3646\u201350.","journal-title":"Stroke."},{"key":"763_CR31","doi-asserted-by":"crossref","unstructured":"Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010. p. e1000412.","DOI":"10.1371\/journal.pbio.1000412"},{"key":"763_CR32","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1161\/01.STR.20.1.84","volume":"20","author":"EZ Longa","year":"1989","unstructured":"Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20:84\u201391.","journal-title":"Stroke."},{"key":"763_CR33","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jneumeth.2011.01.010","volume":"196","author":"A Encarnacion","year":"2011","unstructured":"Encarnacion A, Horie N, Keren-Gill H, Bliss TM, Steinberg GK, Shamloo M. Long-term behavioral assessment of function in an experimental model for ischemic stroke. J Neurosci Methods. 2011;196:247\u201357.","journal-title":"J Neurosci Methods"},{"key":"763_CR34","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1177\/0271678X17709185","volume":"37","author":"N Percie du Sert","year":"2017","unstructured":"Percie du Sert N, Alfieri A, Allan SM, Carswell HV, Deuchar GA, Farr TD, et al. The IMPROVE Guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments). J Cereb Blood Flow Metab. 2017;37:3488\u2013517.","journal-title":"J Cereb Blood Flow Metab"},{"key":"763_CR35","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nprot.2006.19","volume":"1","author":"RMJ Deacon","year":"2006","unstructured":"Deacon RMJ. Burrowing in rodents: a sensitive method for detecting behavioral dysfunction. Nat Protoc. 2006;1:118\u201321.","journal-title":"Nat Protoc"},{"key":"763_CR36","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/nprot.2006.170","volume":"1","author":"RMJ Deacon","year":"2006","unstructured":"Deacon RMJ. Assessing nest building in mice. Nat Protoc. 2006;1:1117\u20139.","journal-title":"Nat Protoc"},{"key":"763_CR37","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","volume":"41","author":"DE Kleiner","year":"2005","unstructured":"Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313\u201321.","journal-title":"Hepatology."},{"key":"763_CR38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","volume":"67","author":"D Bates","year":"2015","unstructured":"Bates D, M\u00e4chler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67:1\u201348.","journal-title":"J Stat Softw"},{"key":"763_CR39","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/10556788.2011.597854","volume":"27","author":"DA Fournier","year":"2012","unstructured":"Fournier DA, Skaug HJ, Ancheta J, Ianelli J, Magnusson A, Maunder MN, et al. AD model builder: using automatic differentiation for statistical inference of highly parameterized complex nonlinear models. Optim Method Softw. 2012;27:233\u201349.","journal-title":"Optim Method Softw"},{"key":"763_CR40","unstructured":"Skaug HJ, Fournier DA, Bolker B, Magnusson A, Nielsen A. Generalized linear mixed models using AD model builder using AD model builder. R Package Version 2016."},{"key":"763_CR41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v069.i01","volume":"69","author":"RV Lenth","year":"2016","unstructured":"Lenth RV. Least-squares means: the RPackage lsmeans. J Stat Softw. 2016;69:1\u201333.","journal-title":"J Stat Softw"},{"key":"763_CR42","unstructured":"R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. R Foundation for Statistical Computing. 2018."},{"key":"763_CR43","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1097\/00001756-200107030-00052","volume":"12","author":"RM Deacon","year":"2001","unstructured":"Deacon RM, Raley JM, Perry VH, Rawlins JN. Burrowing into prion disease. Neuroreport. 2001;12:2053\u20137.","journal-title":"Neuroreport."},{"key":"763_CR44","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.bbi.2007.01.012","volume":"21","author":"JL Teeling","year":"2007","unstructured":"Teeling JL, Felton LM, Deacon RMJ, Cunningham C, Rawlins JNP, Perry VH. Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines. Brain Behav Immun. 2007;21:836\u201350.","journal-title":"Brain Behav Immun"},{"key":"763_CR45","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bbr.2007.12.024","volume":"189","author":"RMJ Deacon","year":"2008","unstructured":"Deacon RMJ, Cholerton LL, Talbot K, Nair-Roberts RG, Sanderson DJ, Romberg C, et al. Age-dependent and -independent behavioral deficits in Tg2576 mice. Behav Brain Res. 2008;189:126\u201338.","journal-title":"Behav Brain Res"},{"key":"763_CR46","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1038\/npp.2013.38","volume":"38","author":"K Takao","year":"2013","unstructured":"Takao K, Kobayashi K, Hagihara H, Ohira K, Shoji H, Hattori S, et al. Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia. Neuropsychopharmacology. 2013;38:1409\u201325.","journal-title":"Neuropsychopharmacology."},{"key":"763_CR47","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bbr.2014.07.023","volume":"273","author":"CS Pedersen","year":"2014","unstructured":"Pedersen CS, S\u00f8rensen DB, Parachikova AI, Plath N. PCP-induced deficits in murine nest building activity: employment of an ethological rodent behavior to mimic negative-like symptoms of schizophrenia. Behav Brain Res. 2014;273:63\u201372.","journal-title":"Behav Brain Res"},{"key":"763_CR48","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s13311-016-0451-5","volume":"13","author":"KJ Becker","year":"2016","unstructured":"Becker KJ. Inflammation and the silent sequelae of stroke. Neurotherapeutics. 2016;13:801\u201310.","journal-title":"Neurotherapeutics."},{"key":"763_CR49","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/1741-7015-10-66","volume":"10","author":"M Maes","year":"2012","unstructured":"Maes M, Berk M, Goehler L, Song C, Anderson G, Ga\u0142ecki P, et al. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med. 2012;10:66.","journal-title":"BMC Med"},{"key":"763_CR50","doi-asserted-by":"crossref","first-page":"e0179588","DOI":"10.1371\/journal.pone.0179588","volume":"12","author":"K Hohlbaum","year":"2017","unstructured":"Hohlbaum K, Bert B, Dietze S, Palme R, Fink H, Th\u00f6ne-Reineke C. Severity classification of repeated isoflurane anesthesia in C57BL\/6JRj mice-assessing the degree of distress. Xie Z, editor. PLoS One. 2017;12:e0179588.","journal-title":"PLoS One"},{"key":"763_CR51","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jamda.2014.12.007","volume":"16","author":"N Scherbakov","year":"2015","unstructured":"Scherbakov N, Sandek A, Doehner W. Stroke-related sarcopenia: specific characteristics. J Am Med Dir Assoc. 2015;16:272\u20136.","journal-title":"J Am Med Dir Assoc"},{"key":"763_CR52","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/00006199-200409000-00001","volume":"53","author":"M-A Choe","year":"2004","unstructured":"Choe M-A, An GJ, Lee Y-K, Im JH, Choi-Kwon S, Heitkemper M. Effect of inactivity and undernutrition after acute ischemic stroke in a rat hindlimb muscle model. Nurs Res. 2004;53:283\u201392.","journal-title":"Nurs Res"},{"key":"763_CR53","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4077\/CJP.2010.AMK080","volume":"53","author":"H-C Chang","year":"2010","unstructured":"Chang H-C, Yang Y-R, Wang PS, Kuo C-H, Wang R-Y. Effects of insulin-like growth factor 1 on muscle atrophy and motor function in rats with brain ischemia. Chin J Physiol. 2010;53:337\u201348.","journal-title":"Chin J Physiol"},{"key":"763_CR54","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1161\/STROKEAHA.114.006258","volume":"45","author":"J Springer","year":"2014","unstructured":"Springer J, Schust S, Peske K, Tschirner A, Rex A, Engel O, et al. Catabolic signaling and muscle wasting after acute ischemic stroke in mice: indication for a stroke-specific sarcopenia. Stroke. 2014;45:3675\u201383.","journal-title":"Stroke."},{"key":"763_CR55","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1161\/STROKEAHA.114.008574","volume":"46","author":"MM Desgeorges","year":"2015","unstructured":"Desgeorges MM, Devillard X, Toutain J, Divoux D, Castells J, Bernaudin M, et al. Molecular mechanisms of skeletal muscle atrophy in a mouse model of cerebral ischemia. Stroke. 2015;46:1673\u201380.","journal-title":"Stroke."},{"key":"763_CR56","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0022-510X(96)00220-1","volume":"144","author":"T Ansved","year":"1996","unstructured":"Ansved T, Ohlsson AL, Jakobsson F, Johansson BB. Enzyme-histochemical and morphological characteristics of fast- and slow-twitch skeletal muscle after brain infarction in the rat. J Neurol Sci. 1996;144:14\u201320.","journal-title":"J Neurol Sci"},{"key":"763_CR57","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1080\/02699050410001672305","volume":"18","author":"M Abo","year":"2004","unstructured":"Abo M, Miyano S, Eun SS, Yamauchi H. Histochemical characterization of skeletal muscles in rats with photochemically-induced stroke. Brain Inj. 2004;18:1017\u201324.","journal-title":"Brain Inj"},{"key":"763_CR58","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1179\/1743132815Y.0000000033","volume":"37","author":"L Cai","year":"2015","unstructured":"Cai L, Geng X, Hussain M, Liu Z, Gao Z, Liu S, et al. Weight loss: indication of brain damage and effect of combined normobaric oxygen and ethanol therapy after stroke. Neurol Res. 2015;37:441\u20136.","journal-title":"Neurol Res"},{"key":"763_CR59","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s12975-011-0102-4","volume":"2","author":"RC Trueman","year":"2011","unstructured":"Trueman RC, Harrison DJ, Dwyer DM, Dunnett SB, Hoehn M, Farr TD. A critical re-examination of the intraluminal filament MCAO model: impact of external carotid artery transection. Transl Stroke Res. 2011;2:651\u201361.","journal-title":"Transl Stroke Res"},{"key":"763_CR60","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1242\/dmm.029108","volume":"10","author":"M Trotman-Lucas","year":"2017","unstructured":"Trotman-Lucas M, Kelly ME, Janus J, Fern R, Gibson CL. An alternative surgical approach reduces variability following filament induction of experimental stroke in mice. Dis Model Mech. 2017;10:931\u20138.","journal-title":"Dis Model Mech"},{"key":"763_CR61","doi-asserted-by":"crossref","first-page":"eaao1313","DOI":"10.1126\/scitranslmed.aao1313","volume":"10","author":"S Roth","year":"2018","unstructured":"Roth S, Singh V, Tiedt S, Schindler L, Huber G, Geerlof A, et al. Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke. Sci Transl Med. 2018;10:eaao1313.","journal-title":"Sci Transl Med"},{"key":"763_CR62","first-page":"603","volume":"33","author":"J Kochanowski","year":"2012","unstructured":"Kochanowski J, Grudniak M, Baranowska-Bik A, Wolinska-Witort E, Kalisz M, Baranowska B, et al. Resistin levels in women with ischemic stroke. Neuro Endocrinol Lett. 2012;33:603\u20137.","journal-title":"Neuro Endocrinol Lett"},{"key":"763_CR63","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.7754\/Clin.Lab.2016.160307","volume":"62","author":"E Perovic","year":"2016","unstructured":"Perovic E, Mrdjen A, Harapin M, Simundic A-M. Short term changes of serum lipids in acute ischemic stroke. Clin Lab. 2016;62:2107\u201313.","journal-title":"Clin Lab"},{"key":"763_CR64","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1080\/10749357.2017.1367454","volume":"24","author":"E Perovic","year":"2017","unstructured":"Perovic E, Mrdjen A, Harapin M, Tesija Kuna A, Simundic A-M. Diagnostic and prognostic role of resistin and copeptin in acute ischemic stroke. Top Stroke Rehabil. 2017;24:614\u20138.","journal-title":"Top Stroke Rehabil"},{"key":"763_CR65","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1161\/STROKEAHA.115.011164","volume":"46","author":"S Yaghi","year":"2015","unstructured":"Yaghi S, Elkind MSV. Lipids and cerebrovascular disease: research and practice. Stroke. 2015;46:3322\u20138.","journal-title":"Stroke."},{"key":"763_CR66","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.atherosclerosis.2013.02.018","volume":"228","author":"G Hao","year":"2013","unstructured":"Hao G, Li W, Guo R, Yang J-G, Wang Y, Tian Y, et al. Serum total adiponectin level and the risk of cardiovascular disease in general population: a meta-analysis of 17 prospective studies. Atherosclerosis. 2013;228:29\u201335.","journal-title":"Atherosclerosis."},{"key":"763_CR67","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.3748\/wjg.v18.i35.4934","volume":"18","author":"W-H Gong","year":"2012","unstructured":"Gong W-H. Coexistence of hyperlipidemia and acute cerebral ischemia\/reperfusion induces severe liver damage in a rat model. WJG. 2012;18:4934.","journal-title":"WJG"},{"key":"763_CR68","doi-asserted-by":"crossref","first-page":"e0184161","DOI":"10.1371\/journal.pone.0184161","volume":"12","author":"M Shaqura","year":"2017","unstructured":"Shaqura M, Mohamed DM, Aboryag NB, Bedewi L, Dehe L, Treskatsch S, et al. Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats. Pant AB, editor. PLoS One. 2017;12:e0184161.","journal-title":"PLoS One"},{"key":"763_CR69","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1210\/en.2013-1593","volume":"155","author":"Y-Y Wang","year":"2014","unstructured":"Wang Y-Y, Lin S-Y, Chuang Y-H, Sheu WH-H, Tung K-C, Chen C-J. Activation of hepatic inflammatory pathways by catecholamines is associated with hepatic insulin resistance in male ischemic stroke rats. Endocrinology. 2014;155:1235\u201346.","journal-title":"Endocrinology."},{"key":"763_CR70","first-page":"1118","volume":"24","author":"X-F Yang","year":"2003","unstructured":"Yang X-F, He W, Lu W-H, Zeng F-D. Effects of scutellarin on liver function after brain ischemia\/reperfusion in rats. Acta Pharmacol Sin. 2003;24:1118\u201324.","journal-title":"Acta Pharmacol Sin"},{"key":"763_CR71","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1111\/j.1532-5415.2006.00921.x","volume":"54","author":"E Elinav","year":"2006","unstructured":"Elinav E, Ackerman Z, Maaravi Y, Ben-Dov IZ, Ein-Mor E, Stessman J. Low alanine aminotransferase activity in older people is associated with greater long-term mortality. J Am Geriatr Soc. 2006;54:1719\u201324.","journal-title":"J Am Geriatr Soc"},{"key":"763_CR72","first-page":"919","volume":"25","author":"E Ramaty","year":"2014","unstructured":"Ramaty E, Maor E, Peltz-Sinvani N, Brom A, Grinfeld A, Kivity S, et al. Low ALT blood levels predict long-term all-cause mortality among adults. A historical prospective cohort study. Eur. J Intern Med. 2014;25:919\u201321.","journal-title":"J Intern Med"},{"key":"763_CR73","first-page":"89\u201393","volume":"154","author":"E Ramati","year":"2015","unstructured":"Ramati E, Israel A, Kessler T, Petz-Sinuani N, Sela BA, Goren I, et al. Low ALT activity amongst patients hospitalized in internal medicine wards is a widespread phenomenon associated with low vitamin B6 levels in their blood. Harefuah. 2015;154:89\u201393\u2013137.","journal-title":"Harefuah"},{"key":"763_CR74","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11606-015-3480-6","volume":"31","author":"N Peltz-Sinvani","year":"2016","unstructured":"Peltz-Sinvani N, Klempfner R, Ramaty E, Sela BA, Goldenberg I, Segal G. Low ALT levels independently associated with 22-year all-cause mortality among coronary heart disease patients. J Gen Intern Med. 2016;31:209\u201314.","journal-title":"J Gen Intern Med"},{"key":"763_CR75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jesf.2017.11.002","volume":"16","author":"M Kogan","year":"2018","unstructured":"Kogan M, Klempfner R, Lotan D, Wasserstrum Y, Goldenberg I, Segal G. Low ALT blood levels are associated with lower baseline fitness amongst participants of a cardiac rehabilitation program. J Exerc Sci Fit. 2018;16:1\u20134.","journal-title":"J Exerc Sci Fit"},{"key":"763_CR76","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1515\/cclm-2017-0311","volume":"56","author":"M Edvardsson","year":"2018","unstructured":"Edvardsson M, Sund-Levander M, Milberg A, Wressle E, Marcusson J, Grodzinsky E. Differences in levels of albumin, ALT, AST, \u03b3-GT and creatinine in frail, moderately healthy and healthy elderly individuals. Clin Chem Lab Med. 2018;56:471\u20138.","journal-title":"Clin Chem Lab Med"},{"key":"763_CR77","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.atherosclerosis.2017.02.005","volume":"260","author":"SU Kim","year":"2017","unstructured":"Kim SU, Song D, Heo JH, Yoo J, Kim BK, Park JY, et al. Liver fibrosis assessed with transient elastography is an independent risk factor for ischemic stroke. Atherosclerosis. 2017;260:156\u201362.","journal-title":"Atherosclerosis"},{"key":"763_CR78","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/MEG.0000000000001011","volume":"30","author":"X Zhang","year":"2018","unstructured":"Zhang X, Qi X, Yoshida EM, M\u00e9ndez-S\u00e1nchez N, Hou F, Deng H, et al. Ischemic stroke in liver cirrhosis: epidemiology, risk factors, and in-hospital outcomes. Eur J Gastroenterol Hepatol. 2018;30:233\u201340.","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"763_CR79","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2147\/NDT.S139316","volume":"13","author":"F Gao","year":"2017","unstructured":"Gao F, Chen C, Lu J, Zheng J, Ma X-C, Yuan X-Y, et al. De Ritis ratio (AST\/ALT) as an independent predictor of poor outcome in patients with acute ischemic stroke. Neuropsychiatr Dis Treat. 2017;13:1551\u20137.","journal-title":"Neuropsychiatr Dis Treat"},{"key":"763_CR80","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1001\/jamaneurol.2014.1017","volume":"71","author":"C Dehlendorff","year":"2014","unstructured":"Dehlendorff C, Andersen KK, Olsen TS. Body mass index and death by stroke: no obesity paradox. JAMA Neurol. 2014;71:978\u201384.","journal-title":"JAMA Neurol"},{"key":"763_CR81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jstrokecerebrovasdis.2012.04.001","volume":"23","author":"RCS Seet","year":"2014","unstructured":"Seet RCS, Zhang Y, Wijdicks EFM, Rabinstein AA. Thrombolysis outcomes among obese and overweight stroke patients: an age- and National Institutes of Health Stroke Scale-matched comparison. J Stroke Cerebrovasc Dis. 2014;23:1\u20136.","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"763_CR82","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1242\/dmm.009068","volume":"5","author":"CB Lawrence","year":"2012","unstructured":"Lawrence CB, Brough D, Knight EM. Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide. Dis Model Mech. 2012;5:649\u201359.","journal-title":"Dis Model Mech"}],"container-title":["Translational Stroke Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-019-00763-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12975-019-00763-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-019-00763-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T00:25:19Z","timestamp":1608423919000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12975-019-00763-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,21]]},"references-count":82,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["763"],"URL":"https:\/\/doi.org\/10.1007\/s12975-019-00763-2","relation":{},"ISSN":["1868-4483","1868-601X"],"issn-type":[{"value":"1868-4483","type":"print"},{"value":"1868-601X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,21]]},"assertion":[{"value":"19 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All scientific procedures using animals were performed in accordance with the Animals (Scientific Procedures) Act 1986 under relevant UK Home Office licences and approved by the local Animal Welfare and Ethical Review Board (University of Manchester, UK). This article does not contain any studies with human participants performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}