{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:45:17Z","timestamp":1793911517699,"version":"4.8.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T00:00:00Z","timestamp":1649289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Shanghai Committee of Science and Technology Project","award":["19140900205"],"award-info":[{"award-number":["19140900205"]}]},{"name":"Shanghai Municipal Health Commission Project","award":["20194Y0444"],"award-info":[{"award-number":["20194Y0444"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1312604"],"award-info":[{"award-number":["2018YFC1312604"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021ZD0201704"],"award-info":[{"award-number":["2021ZD0201704"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008750","name":"Shanghai Hospital Development Center","doi-asserted-by":"publisher","award":["SHDC2020CR3021A"],"award-info":[{"award-number":["SHDC2020CR3021A"]}],"id":[{"id":"10.13039\/501100008750","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuroinflammation is a crucial factor in the development of secondary brain injury after intracerebral hemorrhage (ICH). Irisin is a newly identified myokine that confers strong neuroprotective effects in experimental ischemic stroke. However, whether this myokine can exert neuroprotection effects after ICH remains unknown. This study aimed to investigate the impact of irisin treatment on neuroinflammation and neuronal apoptosis and the underlying mechanism involving integrin \u03b1V\u03b25\/AMPK pathway after ICH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two hundred and eighty-five adult (8-week-old) male C57BL\/6 mice were randomly assigned to sham and ICH surgery groups. ICH was induced via intrastriatal injection of autologous blood. Irisin was administered intranasally at 30\u00a0min after ICH. To elucidate the underlying mechanism, cilengitide (a selective integrin \u03b1V\u03b25 inhibitor) and dorsomorphin (a selective phosphorylated AMPK inhibitor) were administered before irisin treatment. The short- and long-term neurobehavior tests, brain edema, quantitative-PCR, western blotting, Fluoro-Jade C, TUNEL, and immunofluorescence staining were performed to assess the neurofunctional outcome at the level of molecular, cell, histology, and function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Endogenous irisin and its receptor, integrin \u03b1V\u03b25, were increased, peaked at 24\u00a0h after ICH. irisin post-treatment improved both short- and long-term neurological functions, reduced brain edema after ICH. Interestingly, integrin \u03b1V\u03b25 was mainly located in the microglia after ICH, and irisin post-treatment inhibited microglia\/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization. Moreover, irisin treatment inhibited neutrophil infiltration and suppressed neuronal apoptotic cell death in perihematomal areas after ICH. Mechanistically, irisin post-treatment significantly increased the expression of integrin \u03b1V\u03b25, p-AMPK and Bcl-2, and decreased the expression of IL-1\u03b2, TNF-\u03b1, MPO, and Bax following ICH. The neuroprotective effects of irisin were abolished by both integrin \u03b1V\u03b25 inhibitor cilengitide and AMPK inhibitor dorsomorphin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrated that irisin post-treatment ameliorated neurological deficits, reduced brain edema, and ameliorated neuroinflammation and neuronal apoptosis, at least in part, through the integrin \u03b1V\u03b25\/AMPK signaling pathway after ICH. Thus, irisin post-treatment may provide a promising therapeutic approach for the early management of ICH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-022-02438-6","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T04:03:51Z","timestamp":1649304231000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":219,"title":["Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin \u03b1V\u03b25\/AMPK signaling pathway after intracerebral hemorrhage in mice"],"prefix":"10.1186","volume":"19","author":[{"given":"Yao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaocheng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuewen","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuixiang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,7]]},"reference":[{"issue":"8","key":"2438_CR1","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/S1474-4422(12)70104-7","volume":"11","author":"RF Keep","year":"2012","unstructured":"Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720\u201331.","journal-title":"Lancet Neurol"},{"issue":"4","key":"2438_CR2","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s12975-016-0518-y","volume":"8","author":"PA Lapchak","year":"2017","unstructured":"Lapchak PA, Zhang JH. The high cost of stroke and stroke cytoprotection research. Transl Stroke Res. 2017;8(4):307\u201317.","journal-title":"Transl Stroke Res"},{"key":"2438_CR3","doi-asserted-by":"publisher","first-page":"175628642110492","DOI":"10.1177\/17562864211049208","volume":"14","author":"W Bautista","year":"2021","unstructured":"Bautista W, Adelson PD, Bicher N, Themistocleous M, Tsivgoulis G, Chang JJ. Secondary mechanisms of injury and viable pathophysiological targets in intracerebral hemorrhage. Ther Adv Neurol Disord. 2021;14:17562864211049208.","journal-title":"Ther Adv Neurol Disord"},{"key":"2438_CR4","doi-asserted-by":"publisher","first-page":"S142","DOI":"10.1227\/NEU.0000000000000221","volume":"74","author":"M Dey","year":"2014","unstructured":"Dey M, Stadnik A, Awad IA. Spontaneous intracerebral and intraventricular hemorrhage: advances in minimally invasive surgery and thrombolytic evacuation, and lessons learned in recent trials. Neurosurgery. 2014;74:S142\u201350.","journal-title":"Neurosurgery"},{"issue":"1","key":"2438_CR5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1177\/0271678X16679169","volume":"38","author":"A Manaenko","year":"2018","unstructured":"Manaenko A, Yang P, Nowrangi D, Budbazar E, Hartman RE, Obenaus A, Pearce WJ, Zhang JH, Tang J. Inhibition of stress fiber formation preserves blood-brain barrier after intracerebral hemorrhage in mice. J Cereb Blood Flow Metab. 2018;38(1):87\u2013102.","journal-title":"J Cereb Blood Flow Metab"},{"key":"2438_CR6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.5853\/jos.2019.02236","volume":"22","author":"C Tschoe","year":"2020","unstructured":"Tschoe C, Bushnell CD, Duncan PW, Alexander-Miller MA, Wolfe SQ. Neuroinflammation after intracerebral hemorrhage and potential therapeutic targets. J Stroke. 2020;22:29\u201346.","journal-title":"J Stroke"},{"key":"2438_CR7","doi-asserted-by":"publisher","first-page":"101610","DOI":"10.1016\/j.pneurobio.2019.03.003","volume":"178","author":"H Zhu","year":"2019","unstructured":"Zhu H, Wang Z, Yu J, Yang X, He F, Liu Z, Che F, Chen X, Ren H, Hong M, Wang J. Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage. Prog Neurobiol. 2019;178:101610.","journal-title":"Prog Neurobiol"},{"issue":"5","key":"2438_CR8","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1007\/s12975-019-00768-x","volume":"11","author":"X Wu","year":"2020","unstructured":"Wu X, Luo J, Liu H, Cui W, Guo K, Zhao L, Bai H, Guo W, Guo H, Feng D, Qu Y. Recombinant adiponectin peptide ameliorates brain injury following intracerebral hemorrhage by suppressing astrocyte-derived inflammation via the inhibition of Drp1-mediated mitochondrial fission. Transl Stroke Res. 2020;11(5):924\u201339.","journal-title":"Transl Stroke Res"},{"issue":"1","key":"2438_CR9","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s12974-019-1591-4","volume":"16","author":"X Wu","year":"2019","unstructured":"Wu X, Fu S, Liu Y, Luo H, Li F, Wang Y, Gao M, Cheng Y, Xie Z. NDP-MSH binding melanocortin-1 receptor ameliorates neuroinflammation and BBB disruption through CREB\/Nr4a1\/NF-\u03baB pathway after intracerebral hemorrhage in mice. J Neuroinflammation. 2019;16(1):192.","journal-title":"J Neuroinflammation"},{"key":"2438_CR10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.pneurobio.2013.11.003","volume":"115","author":"Y Zhou","year":"2014","unstructured":"Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol. 2014;115:25\u201344.","journal-title":"Prog Neurobiol"},{"key":"2438_CR11","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s12974-017-1005-4","volume":"14","author":"CH Wu","year":"2017","unstructured":"Wu CH, Shyue SK, Hung TH, Wen S, Lin CC, Chang CF, Chen SF. Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase reduces brain damage and attenuates neuroinflammation after intracerebral hemorrhage. J Neuroinflammation. 2017;14:230.","journal-title":"J Neuroinflammation"},{"key":"2438_CR12","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s12975-014-0384-4","volume":"6","author":"S Chen","year":"2015","unstructured":"Chen S, Yang Q, Chen G, Zhang JH. An update on inflammation in the acute phase of intracerebral hemorrhage. Transl Stroke Res. 2015;6:4\u20138.","journal-title":"Transl Stroke Res"},{"key":"2438_CR13","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/nri2215","volume":"8","author":"H Kono","year":"2008","unstructured":"Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 2008;8:279\u201389.","journal-title":"Nat Rev Immunol"},{"issue":"4","key":"2438_CR14","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/j.cmet.2015.08.001","volume":"22","author":"MP Jedrychowski","year":"2015","unstructured":"Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM, Nair KS, Gygi SP, Spiegelman BM. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 2015;22(4):734\u201340.","journal-title":"Cell Metab"},{"issue":"7382","key":"2438_CR15","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/nature10777","volume":"481","author":"P Bostr\u00f6m","year":"2012","unstructured":"Bostr\u00f6m P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostr\u00f6m EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, H\u00f8jlund K, Gygi SP, Spiegelman BM. A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463\u20138.","journal-title":"Nature"},{"issue":"5","key":"2438_CR16","doi-asserted-by":"publisher","first-page":"E512","DOI":"10.1152\/ajpendo.00308.2013","volume":"306","author":"MK Piya","year":"2014","unstructured":"Piya MK, Harte AL, Sivakumar K, Tripathi G, Voyias PD, James S, Sabico S, Al-Daghri NM, Saravanan P, Barber TM, Kumar S, Vatish M, McTernan PG. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. Am J Physiol Endocrinol Metab. 2014;306(5):E512\u20138.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"5","key":"2438_CR17","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","volume":"18","author":"CD Wrann","year":"2013","unstructured":"Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM. Exercise induces hippocampal BDNF through a PGC-1\u03b1\/FNDC5 pathway. Cell Metab. 2013;18(5):649\u201359.","journal-title":"Cell Metab"},{"key":"2438_CR18","doi-asserted-by":"publisher","first-page":"9070341","DOI":"10.1155\/2018\/9070341","volume":"2018","author":"K Wang","year":"2018","unstructured":"Wang K, Li H, Wang H, Wang JH, Song F, Sun Y. Irisin exerts neuroprotective effects on cultured neurons by regulating astrocytes. Mediators Inflamm. 2018;2018:9070341.","journal-title":"Mediators Inflamm"},{"issue":"8","key":"2438_CR19","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1038\/s42255-021-00438-z","volume":"3","author":"MR Islam","year":"2021","unstructured":"Islam MR, Valaris S, Young MF, Haley EB, Luo R, Bond SF, Mazuera S, Kitchen RR, Caldarone BJ, Bettio LEB, Christie BR, Schmider AB, Soberman RJ, Besnard A, Jedrychowski MP, Kim H, Tu H, Kim E, Choi SH, Tanzi RE, Spiegelman BM, Wrann CD. Exercise hormone irisin is a critical regulator of cognitive function. Nat Metab. 2021;3(8):1058\u201370.","journal-title":"Nat Metab"},{"issue":"1","key":"2438_CR20","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41591-018-0275-4","volume":"25","author":"MV Lourenco","year":"2019","unstructured":"Lourenco MV, Frozza RL, de Freitas GB, Zhang H, Kincheski GC, Ribeiro FC, Gon\u00e7alves RA, Clarke JR, Beckman D, Staniszewski A, Berman H, Guerra LA, Forny-Germano L, Meier S, Wilcock DM, de Souza JM, Alves-Leon S, Prado VF, Prado MAM, Abisambra JF, Tovar-Moll F, Mattos P, Arancio O, Ferreira ST, De Felice FG. Exercise-linked FNDC5\/irisin rescues synaptic plasticity and memory defects in Alzheimer\u2019s models. Nat Med. 2019;25(1):165\u201375.","journal-title":"Nat Med"},{"key":"2438_CR21","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.metabol.2016.12.003","volume":"68","author":"DJ Li","year":"2017","unstructured":"Li DJ, Li YH, Yuan HB, Qu LF, Wang P. The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1\/2 signaling pathways and contributes to the neuroprotection of physical exercise in cerebral ischemia. Metabolism. 2017;68:31\u201342.","journal-title":"Metabolism"},{"key":"2438_CR22","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.phrs.2018.01.012","volume":"129","author":"H Askari","year":"2018","unstructured":"Askari H, Rajani SF, Poorebrahim M, Haghi-Aminjan H, Raeis-Abdollahi E, Abdollahi M. A glance at the therapeutic potential of irisin against diseases involving inflammation, oxidative stress, and apoptosis: an introductory review. Pharmacol Res. 2018;129:44\u201355.","journal-title":"Pharmacol Res"},{"issue":"2","key":"2438_CR23","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.cell.2019.06.028","volume":"178","author":"H Kim","year":"2019","unstructured":"Kim H, Wrann CD, Jedrychowski M, Vidoni S, Kitase Y, Nagano K, Zhou C, Chou J, Parkman VA, Novick SJ, Strutzenberg TS, Pascal BD, Le PT, Brooks DJ, Roche AM, Gerber KK, Mattheis L, Chen W, Tu H, Bouxsein ML, Griffin PR, Baron R, Rosen CJ, Bonewald LF, Spiegelman BM. Irisin mediates effects on bone and fat via \u03b1V integrin receptors. Cell. 2019;178(2):507\u20138.","journal-title":"Cell"},{"issue":"1","key":"2438_CR24","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1111\/jcmm.14811","volume":"24","author":"J Bi","year":"2020","unstructured":"Bi J, Zhang J, Ren Y, Du Z, Li T, Wang T, Zhang L, Wang M, Wu Z, Lv Y, Wu R. Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin \u03b1V\u03b25 receptor. J Cell Mol Med. 2020;24(1):996\u20131009.","journal-title":"J Cell Mol Med"},{"key":"2438_CR25","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/1742-2094-8-157","volume":"8","author":"JV Welser-Alves","year":"2011","unstructured":"Welser-Alves JV, Boroujerdi A, Tigges U, Milner R. Microglia use multiple mechanisms to mediate interactions with vitronectin; non-essential roles for the highly-expressed \u03b1v\u03b23 and \u03b1v\u03b25 integrins. J Neuroinflammation. 2011;8:157.","journal-title":"J Neuroinflammation"},{"key":"2438_CR26","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.redox.2017.12.019","volume":"15","author":"H Zhou","year":"2018","unstructured":"Zhou H, Wang S, Zhu P, Hu S, Chen Y, Ren J. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission. Redox Biol. 2018;15:335\u201346.","journal-title":"Redox Biol"},{"issue":"2","key":"2438_CR27","doi-asserted-by":"publisher","first-page":"e12542","DOI":"10.1111\/jpi.12542","volume":"66","author":"Y Zhang","year":"2019","unstructured":"Zhang Y, Wang Y, Xu J, Tian F, Hu S, Chen Y, Fu Z. Melatonin attenuates myocardial ischemia-reperfusion injury via improving mitochondrial fusion\/mitophagy and activating the AMPK-OPA1 signaling pathways. J Pineal Res. 2019;66(2):e12542.","journal-title":"J Pineal Res"},{"issue":"16","key":"2438_CR28","doi-asserted-by":"publisher","first-page":"4535","DOI":"10.7150\/thno.25674","volume":"8","author":"S Jiang","year":"2018","unstructured":"Jiang S, Li T, Ji T, Yi W, Yang Z, Wang S, Yang Y, Gu C. AMPK: potential therapeutic target for ischemic stroke. Theranostics. 2018;8(16):4535\u201351.","journal-title":"Theranostics"},{"key":"2438_CR29","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3389\/fimmu.2020.00041","volume":"11","author":"B Liu","year":"2020","unstructured":"Liu B, Huang B, Hu G, He D, Li Y, Ran X, Du J, Fu S, Liu D. Isovitexin-mediated regulation of microglial polarization in lipopolysaccharide-induced neuroinflammation via activation of the CaMKK\u03b2\/AMPK-PGC-1\u03b1 signaling axis. Front Immunol. 2020;11:41.","journal-title":"Front Immunol"},{"issue":"12","key":"2438_CR30","doi-asserted-by":"publisher","first-page":"6009","DOI":"10.4049\/jimmunol.1303492","volume":"192","author":"L Xie","year":"2014","unstructured":"Xie L, Sun F, Wang J, Mao X, Xie L, Yang SH, Su DM, Simpkins JW, Greenberg DA, Jin K. mTOR signaling inhibition modulates macrophage\/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia. J Immunol. 2014;192(12):6009\u201319.","journal-title":"J Immunol"},{"issue":"10","key":"2438_CR31","doi-asserted-by":"publisher","first-page":"3388","DOI":"10.1096\/fj.201600495R","volume":"30","author":"D Li","year":"2016","unstructured":"Li D, Wang C, Yao Y, Chen L, Liu G, Zhang R, Liu Q, Shi FD, Hao J. mTORC1 pathway disruption ameliorates brain inflammation following stroke via a shift in microglia phenotype from M1 type to M2 type. FASEB J. 2016;30(10):3388\u201399.","journal-title":"FASEB J"},{"issue":"2","key":"2438_CR32","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrm.2017.95","volume":"19","author":"S Herzig","year":"2018","unstructured":"Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018;19(2):121\u201335.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"13","key":"2438_CR33","doi-asserted-by":"publisher","first-page":"e136277","DOI":"10.1172\/jci.insight.136277","volume":"5","author":"J Bi","year":"2020","unstructured":"Bi J, Zhang J, Ren Y, Du Z, Zhang Y, Liu C, Wang Y, Zhang L, Shi Z, Wu Z, Lv Y, Wu R. Exercise hormone irisin mitigates endothelial barrier dysfunction and microvascular leakage-related diseases. JCI Insight. 2020;5(13):e136277.","journal-title":"JCI Insight."},{"issue":"3","key":"2438_CR34","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1007\/s13311-019-00821-5","volume":"17","author":"J Yan","year":"2020","unstructured":"Yan J, Zuo G, Sherchan P, Huang L, Ocak U, Xu W, Travis ZD, Wang W, Zhang JH, Tang J. CCR1 activation promotes neuroinflammation through CCR1\/TPR1\/ERK1\/2 signaling pathway after intracerebral hemorrhage in mice. Neurotherapeutics. 2020;17(3):1170\u201383.","journal-title":"Neurotherapeutics"},{"key":"2438_CR35","doi-asserted-by":"publisher","first-page":"640215","DOI":"10.3389\/fnagi.2021.640215","volume":"13","author":"T Tu","year":"2021","unstructured":"Tu T, Yin S, Pang J, Zhang X, Zhang L, Zhang Y, Xie Y, Guo K, Chen L, Peng J, Jiang Y. Irisin contributes to neuroprotection by promoting mitochondrial biogenesis after experimental subarachnoid hemorrhage. Front Aging Neurosci. 2021;13:640215.","journal-title":"Front Aging Neurosci."},{"issue":"7","key":"2438_CR36","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1007\/s00221-021-06111-x","volume":"239","author":"J Wang","year":"2021","unstructured":"Wang J, Wang Y, Zuo Y, Duan J, Pan A, Li JM, Yan XX, Liu F. MFGE8 mitigates brain injury in a rat model of SAH by maintaining vascular endothelial integrity via TIG\u03b25\/PI3K\/CXCL12 signaling. Exp Brain Res. 2021;239(7):2193\u2013205.","journal-title":"Exp Brain Res"},{"issue":"1","key":"2438_CR37","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/s12974-018-1256-8","volume":"15","author":"L Zhao","year":"2018","unstructured":"Zhao L, Chen S, Sherchan P, Ding Y, Zhao W, Guo Z, Yu J, Tang J, Zhang JH. Recombinant CTRP9 administration attenuates neuroinflammation via activating adiponectin receptor 1 after intracerebral hemorrhage in mice. J Neuroinflammation. 2018;15(1):215.","journal-title":"J Neuroinflammation"},{"issue":"12","key":"2438_CR38","doi-asserted-by":"publisher","first-page":"4021","DOI":"10.1161\/STROKEAHA.120.033285","volume":"52","author":"J Yan","year":"2021","unstructured":"Yan J, Xu W, Lenahan C, Huang L, Wen J, Li G, Hu X, Zheng W, Zhang JH, Tang J. CCR5 activation promotes NLRP1-dependent neuronal pyroptosis via CCR5\/PKA\/CREB pathway after intracerebral hemorrhage. Stroke. 2021;52(12):4021\u201332.","journal-title":"Stroke"},{"key":"2438_CR39","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1177\/0271678X16658490","volume":"37","author":"LS Tong","year":"2017","unstructured":"Tong LS, Shao AW, Ou YB, Guo ZN, Manaenko A, Dixon BJ, Tang J, Lou M, Zhang JH. Recombinant Gas6 augments Axl and facilitates immune restoration in an intracerebral hemorrhage mouse model. J Cereb Blood Flow Metab. 2017;37:1971\u201381.","journal-title":"J Cereb Blood Flow Metab"},{"key":"2438_CR40","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.1161\/STROKEAHA.118.022155","volume":"49","author":"G Wang","year":"2018","unstructured":"Wang G, Guo Z, Tong L, Xue F, Krafft PR, Budbazar E, Zhang JH, Tang J. TLR7 (Toll-like receptor 7) facilitates heme scavenging through the BTK (Bruton Tyrosine Kinase)-CRT (Calreticulin)-LRP1 (Low-Density Lipoprotein Receptor-Related Protein-1)-Hx (Hemopexin) pathway in murine intracerebral hemorrhage. Stroke. 2018;49:3020\u20139.","journal-title":"Stroke"},{"issue":"6","key":"2438_CR41","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101\u20138.","journal-title":"Nat Protoc"},{"issue":"1","key":"2438_CR42","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12974-018-1140-6","volume":"15","author":"S Chen","year":"2018","unstructured":"Chen S, Zhao L, Sherchan P, Ding Y, Yu J, Nowrangi D, Tang J, Xia Y, Zhang JH. Activation of melanocortin receptor 4 with RO27-3225 attenuates neuroinflammation through AMPK\/JNK\/p38 MAPK pathway after intracerebral hemorrhage in mice. J Neuroinflammation. 2018;15(1):106.","journal-title":"J Neuroinflammation"},{"key":"2438_CR43","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.redox.2018.09.022","volume":"20","author":"J Mo","year":"2019","unstructured":"Mo J, Enkhjargal B, Travis ZD, Zhou K, Wu P, Zhang G, Zhu Q, Zhang T, Peng J, Xu W, Ocak U, Chen Y, Tang J, Zhang J, Zhang JH. AVE 0991 attenuates oxidative stress and neuronal apoptosis via Mas\/PKA\/CREB\/UCP-2 pathway after subarachnoid hemorrhage in rats. Redox Biol. 2019;20:75\u201386.","journal-title":"Redox Biol"},{"key":"2438_CR44","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.freeradbiomed.2019.09.002","volume":"143","author":"G Zuo","year":"2019","unstructured":"Zuo G, Zhang T, Huang L, Araujo C, Peng J, Travis Z, Okada T, Ocak U, Zhang G, Tang J, Lu X, Zhang JH. Activation of TGR5 with INT-777 attenuates oxidative stress and neuronal apoptosis via cAMP\/PKC\u03b5\/ALDH2 pathway after subarachnoid hemorrhage in rats. Free Radical Biol Med. 2019;143:441\u201353.","journal-title":"Free Radical Biol Med"},{"key":"2438_CR45","doi-asserted-by":"publisher","first-page":"118813","DOI":"10.1016\/j.ijpharm.2019.118813","volume":"572","author":"Y Lobaina Mato","year":"2019","unstructured":"Lobaina Mato Y. Nasal route for vaccine and drug delivery: features and current opportunities. Int J Pharm. 2019;572:118813.","journal-title":"Int J Pharm"},{"key":"2438_CR46","doi-asserted-by":"publisher","first-page":"588958","DOI":"10.3389\/fnagi.2020.588958","volume":"12","author":"Y Liu","year":"2020","unstructured":"Liu Y, Zhu C, Guo J, Chen Y, Meng C. The neuroprotective effect of irisin in ischemic stroke. Front Aging Neurosci. 2020;12:588958.","journal-title":"Front Aging Neurosci."},{"issue":"8","key":"2438_CR47","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1007\/s11064-018-2569-9","volume":"43","author":"Y Asadi","year":"2018","unstructured":"Asadi Y, Gorjipour F, Behrouzifar S, Vakili A. Irisin peptide protects brain against ischemic injury through reducing apoptosis and enhancing BDNF in a rodent model of stroke. Neurochem Res. 2018;43(8):1549\u201360.","journal-title":"Neurochem Res"},{"issue":"1","key":"2438_CR48","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12974-018-1177-6","volume":"15","author":"WJ Tu","year":"2018","unstructured":"Tu WJ, Qiu HC, Liu Q, Li X, Zhao JZ, Zeng X. Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population. J Neuroinflammation. 2018;15(1):133.","journal-title":"J Neuroinflammation"},{"issue":"4","key":"2438_CR49","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1007\/s13311-018-0651-2","volume":"15","author":"WJ Tu","year":"2018","unstructured":"Tu WJ, Qiu HC, Cao JL, Liu Q, Zeng XW, Zhao JZ. Decreased concentration of irisin is associated with poor functional outcome in ischemic stroke. Neurotherapeutics. 2018;15(4):1158\u201367.","journal-title":"Neurotherapeutics"},{"issue":"3","key":"2438_CR50","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1590\/1516-4446-2013-1233","volume":"36","author":"F Dal-Pizzol","year":"2014","unstructured":"Dal-Pizzol F, Tomasi CD, Ritter C. Septic encephalopathy: does inflammation drive the brain crazy? Braz J Psychiatry. 2014;36(3):251\u20138.","journal-title":"Braz J Psychiatry"},{"issue":"4","key":"2438_CR51","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1007\/s13311-016-0463-1","volume":"13","author":"E Kim","year":"2016","unstructured":"Kim E, Cho S. Microglia and monocyte-derived macrophages in stroke. Neurotherapeutics. 2016;13(4):702\u201318.","journal-title":"Neurotherapeutics"},{"key":"2438_CR52","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.nbd.2017.03.016","volume":"103","author":"CF Chang","year":"2017","unstructured":"Chang CF, Wan J, Li Q, Renfroe SC, Heller NM, Wang J. Alternative activation-skewed microglia\/macrophages promote hematoma resolution in experimental intracerebral hemorrhage. Neurobiol Dis. 2017;103:54\u201369.","journal-title":"Neurobiol Dis"},{"issue":"8","key":"2438_CR53","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1038\/nn.4338","volume":"19","author":"RM Ransohoff","year":"2016","unstructured":"Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci. 2016;19(8):987\u201391.","journal-title":"Nat Neurosci"},{"issue":"1","key":"2438_CR54","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1172\/JCI88647","volume":"127","author":"RA Taylor","year":"2017","unstructured":"Taylor RA, Chang CF, Goods BA, Hammond MD, Mac Grory B, Ai Y, Steinschneider AF, Renfroe SC, Askenase MH, McCullough LD, Kasner SE, Mullen MT, Hafler DA, Love JC, Sansing LH. TGF-\u03b21 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage. J Clin Invest. 2017;127(1):280\u201392.","journal-title":"J Clin Invest"},{"issue":"7","key":"2438_CR55","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/nrneurol.2017.69","volume":"13","author":"X Lan","year":"2017","unstructured":"Lan X, Han X, Li Q, Yang QW, Wang J. Modulators of microglial activation and polarization after intracerebral haemorrhage. Nat Rev Neurol. 2017;13(7):420\u201333.","journal-title":"Nat Rev Neurol"},{"key":"2438_CR56","doi-asserted-by":"publisher","first-page":"584","DOI":"10.4049\/jimmunol.1401024","volume":"194","author":"YP Zhu","year":"2015","unstructured":"Zhu YP, Brown JR, Sag D, Zhang L, Suttles J. Adenosine 5\u2032-monophosphate-activated protein kinase regulates IL-10-mediated anti-inflammatory signaling pathways in macrophages. J Immunol. 2015;194:584\u201394.","journal-title":"J Immunol"},{"key":"2438_CR57","doi-asserted-by":"publisher","first-page":"3725","DOI":"10.1161\/STROKEAHA.114.005377","volume":"45","author":"PD Hurn","year":"2014","unstructured":"Hurn PD. 2014 Thomas Willis Award Lecture: sex, stroke, and innovation. Stroke. 2014;45:3725\u20139.","journal-title":"Stroke"},{"key":"2438_CR58","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1161\/01.STR.0000145485.67827.d0","volume":"35","author":"Y Gong","year":"2004","unstructured":"Gong Y, Hua Y, Keep RF, Hoff JT, Xi G. Intracerebral hemorrhage: effects of aging on brain edema and neurological deficits. Stroke. 2004;35:2571\u20135.","journal-title":"Stroke"},{"key":"2438_CR59","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3171\/jns.2005.103.1.0097","volume":"103","author":"T Nakamura","year":"2005","unstructured":"Nakamura T, Hua Y, Keep RF, Park JW, Xi G, Hoff JT. Estrogen therapy for experimental intracerebral hemorrhage in rats. J Neurosurg. 2005;103:97\u2013103.","journal-title":"J Neurosurg"},{"issue":"2","key":"2438_CR60","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s12975-018-0633-z","volume":"10","author":"Y Xie","year":"2019","unstructured":"Xie Y, Li YJ, Lei B, Kernagis D, Liu WW, Bennett ER, Venkatraman T, Lascola CD, Laskowitz DT, Warner DS, James ML. Sex differences in gene and protein expression after intracerebral hemorrhage in mice. Transl Stroke Res. 2019;10(2):231\u20139.","journal-title":"Transl Stroke Res"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02438-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-022-02438-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02438-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T06:10:14Z","timestamp":1666419014000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-022-02438-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,7]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2438"],"URL":"https:\/\/doi.org\/10.1186\/s12974-022-02438-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1345807\/v1","asserted-by":"object"}]},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,7]]},"assertion":[{"value":"10 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments in the study were approved by the Animal Care and Use Committee of Shanghai Medical College, Fudan University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"82"}}