{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:45:49Z","timestamp":1787622349954,"version":"build-2736575974"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,7]],"date-time":"2019-01-07T00:00:00Z","timestamp":1546819200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Science Fund for Distinguished Young Scholars","award":["81625012"],"award-info":[{"award-number":["81625012"]}]},{"name":"the Science Fund for Creative Research Groups of the National Natural Science Foundation of China","award":["61721092"],"award-info":[{"award-number":["61721092"]}]},{"name":"Program for HUST Academic Frontier Youth Team"},{"name":"the Fundamental Research Funds for the Central Universities","award":["2015ZDTD014, 2018KFYXKJC040"],"award-info":[{"award-number":["2015ZDTD014, 2018KFYXKJC040"]}]},{"name":"the Director Fund of WNLO"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s12974-018-1389-9","type":"journal-article","created":{"date-parts":[[2019,1,7]],"date-time":"2019-01-07T15:54:23Z","timestamp":1546876463000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Long-term characterization of activated microglia\/macrophages facilitating the development of experimental brain metastasis through intravital microscopic imaging"],"prefix":"10.1186","volume":"16","author":[{"given":"Sha","family":"Qiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5227-8926","authenticated-orcid":false,"given":"Zhihong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,7]]},"reference":[{"key":"1389_CR1","first-page":"49","volume":"2017","author":"FJ Lowery","year":"1867","unstructured":"Lowery FJ, Yu D. Brain metastasis: unique challenges and open opportunities. Biochim Biophys Acta. 1867;2017:49\u201357.","journal-title":"Biochim Biophys Acta"},{"key":"1389_CR2","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s00401-011-0933-9","volume":"123","author":"M Preusser","year":"2012","unstructured":"Preusser M, Capper D, Ilhan-Mutlu A, Berghoff AS, Birner P, Bartsch R, et al. Brain metastases: pathobiology and emerging targeted therapies. Acta Neuropathol. 2012;123:205\u201322.","journal-title":"Acta Neuropathol"},{"key":"1389_CR3","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/nrc3053","volume":"11","author":"PS Steeg","year":"2011","unstructured":"Steeg PS, Camphausen KA, Smith QR. Brain metastases as preventive and therapeutic targets. Nat Rev Cancer. 2011;11:352\u201363.","journal-title":"Nat Rev Cancer"},{"key":"1389_CR4","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1038\/nn1997","volume":"10","author":"U-K Hanisch","year":"2007","unstructured":"Hanisch U-K, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10:1387\u201394.","journal-title":"Nat Neurosci"},{"key":"1389_CR5","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1146\/annurev-immunol-032713-120240","volume":"32","author":"D Nayak","year":"2014","unstructured":"Nayak D, Roth TL, McGavern DB. Microglia development and function. Annu Rev Immunol. 2014;32:367\u2013402.","journal-title":"Annu Rev Immunol"},{"key":"1389_CR6","first-page":"198","volume":"8","author":"C Sousa","year":"2017","unstructured":"Sousa C, Biber K, Michelucci A. Cellular and molecular characterization of microglia: a unique immune cell population. Front Immunol. 2017;8:198.","journal-title":"Front Immunol"},{"key":"1389_CR7","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1146\/annurev-physiol-022516-034406","volume":"79","author":"SA Wolf","year":"2017","unstructured":"Wolf SA, Boddeke HWGM, Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol. 2017;79:619\u201343.","journal-title":"Annu Rev Physiol"},{"key":"1389_CR8","first-page":"21","volume":"41","author":"B Kwon","year":"2017","unstructured":"Kwon B. IFN-\u03b3 in tissue-immune homeostasis and antitumor immunity. Cell Mol Immunol. 2017;41:21.","journal-title":"Cell Mol Immunol"},{"key":"1389_CR9","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/nn.4185","volume":"19","author":"D Hambardzumyan","year":"2016","unstructured":"Hambardzumyan D, Gutmann DH, Kettenmann H. The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci. 2016;19:20\u20137.","journal-title":"Nat Neurosci"},{"key":"1389_CR10","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.jneuroim.2008.04.016","volume":"198","author":"C Liu","year":"2008","unstructured":"Liu C, Luo D, Streit WJ, Harrison JK. CX3CL1 and CX3CR1 in the GL261 murine model of glioma: CX3CR1 deficiency does not impact tumor growth or infiltration of microglia and lymphocytes. J Neuroimmunol. 2008;198:98\u2013105.","journal-title":"J Neuroimmunol"},{"key":"1389_CR11","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1111\/pcmr.12538","volume":"29","author":"JV Cohen","year":"2016","unstructured":"Cohen JV, Tawbi H, Margolin KA, Amravadi R, Bosenberg M, Brastianos PK, et al. Melanoma central nervous system metastases: current approaches, challenges, and opportunities. Pigment Cell Melanoma Res. 2016;29:627\u201342.","journal-title":"Pigment Cell Melanoma Res"},{"key":"1389_CR12","doi-asserted-by":"publisher","first-page":"2904","DOI":"10.1007\/s11095-016-2012-3","volume":"33","author":"R Samala","year":"2016","unstructured":"Samala R, Thorsheim HR, Goda S, Taskar K, Gril B, Steeg PS, et al. Vinorelbine delivery and efficacy in the MDA-MB-231BR preclinical model of brain metastases of breast cancer. Pharm Res. 2016;33:2904\u201319.","journal-title":"Pharm Res"},{"key":"1389_CR13","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nrneurol.2014.207","volume":"11","author":"X Hu","year":"2015","unstructured":"Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, et al. Microglial and macrophage polarization\u2014new prospects for brain repair. Nat Rev Neurol. 2015;11:56\u201364.","journal-title":"Nat Rev Neurol"},{"key":"1389_CR14","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/nrn3722","volume":"15","author":"M Prinz","year":"2014","unstructured":"Prinz M, Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci. 2014;15:300\u201312.","journal-title":"Nat Rev Neurosci"},{"key":"1389_CR15","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1002\/glia.21022","volume":"58","author":"T Pukrop","year":"2010","unstructured":"Pukrop T, Dehghani F, Chuang H-N, Lohaus R, Bayanga K, Heermann S, et al. Microglia promote colonization of brain tissue by breast cancer cells in a Wnt-dependent way. Glia. 2010;58:1477\u201389.","journal-title":"Glia"},{"key":"1389_CR16","doi-asserted-by":"publisher","first-page":"161","DOI":"10.2119\/2006-00033.He","volume":"12","author":"BP He","year":"2006","unstructured":"He BP, Wang JJ, Zhang X, Wu Y, Wang M, Bay B-H, Chang AY-C. Differential reactions of microglia to brain metastasis of lung cancer. Mol Med. 2006;12:161\u201370.","journal-title":"Mol Med"},{"key":"1389_CR17","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1593\/tlo.10208","volume":"3","author":"EC Brantley","year":"2010","unstructured":"Brantley EC, Guo L, Zhang C, Lin Q, Yokoi K, Langley RR, et al. Nitric oxide-mediated tumoricidal activity of murine microglial cells. Transl Oncol. 2010;3:380\u20138.","journal-title":"Transl Oncol"},{"key":"1389_CR18","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/nri3086","volume":"11","author":"K Saijo","year":"2011","unstructured":"Saijo K, Glass CK. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol. 2011;11:775\u201387.","journal-title":"Nat Rev Immunol"},{"key":"1389_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fncel.2013.00003","volume":"7","author":"A Karperien","year":"2013","unstructured":"Karperien A, Ahammer H, Jelinek HF. Quantitating the subtleties of microglial morphology with fractal analysis. Front Cell Neurosci. 2013;7:3.","journal-title":"Front Cell Neurosci"},{"key":"1389_CR20","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1002\/glia.23046","volume":"64","author":"A Sierra","year":"2016","unstructured":"Sierra A, de Castro F, del R\u00edo-Hortega J, Rafael Iglesias-Rozas J, Garrosa M, Kettenmann H. The \u201cbig-bang\u201d for modern glial biology: translation and comments on P\u00edo del R\u00edo-Hortega 1919 series of papers on microglia. Glia. 2016;64:1801\u201340.","journal-title":"Glia"},{"key":"1389_CR21","doi-asserted-by":"publisher","first-page":"275","DOI":"10.2967\/jnumed.113.127449","volume":"55","author":"ER O'Brien","year":"2014","unstructured":"O'Brien ER, Kersemans V, Tredwell M, Checa B, Serres S, Soto MS, et al. Glial activation in the early stages of brain metastasis: TSPO as a diagnostic biomarker. J Nucl Med. 2014;55:275\u201380.","journal-title":"J Nucl Med"},{"key":"1389_CR22","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1002\/glia.22998","volume":"64","author":"GA Garden","year":"2016","unstructured":"Garden GA, Campbell BM. Glial biomarkers in human central nervous system disease. Glia. 2016;64:1755\u201371.","journal-title":"Glia"},{"key":"1389_CR23","doi-asserted-by":"publisher","first-page":"10954","DOI":"10.1073\/pnas.97.20.10954","volume":"97","author":"R Wada","year":"2000","unstructured":"Wada R, Tifft CJ, Proia RL. Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. Proc Natl Acad Sci U S A. 2000;97:10954\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1389_CR24","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1126\/science.1110647","volume":"308","author":"A Nimmerjahn","year":"2005","unstructured":"Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308:1314\u20138.","journal-title":"Science"},{"key":"1389_CR25","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1002\/1098-1136(200103)33:3<256::AID-GLIA1024>3.0.CO;2-J","volume":"33","author":"N Stence","year":"2001","unstructured":"Stence N, Waite M, Dailey ME. Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal slices. Glia. 2001;33:256\u201366.","journal-title":"Glia"},{"key":"1389_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/cmi.2014.83","volume":"12","author":"Y Liu","year":"2015","unstructured":"Liu Y, Cao X. The origin and function of tumor-associated macrophages. Cell Mol Immunol. 2015;12:1\u20134.","journal-title":"Cell Mol Immunol"},{"key":"1389_CR27","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s10585-005-8115-6","volume":"22","author":"O Mendes","year":"2005","unstructured":"Mendes O, Kim H-T, Stoica G. Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model. Clin Exp Metastasis. 2005;22:237\u201346.","journal-title":"Clin Exp Metastasis"},{"key":"1389_CR28","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s10585-007-9071-0","volume":"24","author":"O Mendes","year":"2007","unstructured":"Mendes O, Kim H-T, Lungu G, Stoica G. MMP2 role in breast cancer brain metastasis development and its regulation by TIMP2 and ERK1\/2. Clin Exp Metastasis. 2007;24:341\u201351.","journal-title":"Clin Exp Metastasis"},{"key":"1389_CR29","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s11060-006-9207-0","volume":"81","author":"AM Stark","year":"2007","unstructured":"Stark AM, Anuszkiewicz B, Mentlein R, Yoneda T, Mehdorn HM, Held-Feindt J. Differential expression of matrix metalloproteinases in brain- and bone-seeking clones of metastatic MDA-MB-231 breast cancer cells. J Neuro-Oncol. 2007;81:39\u201348.","journal-title":"J Neuro-Oncol"},{"key":"1389_CR30","doi-asserted-by":"crossref","unstructured":"Semyachkina-Glushkovskaya OV, Abdurashitov AS, Saranceva EI, Borisova EG, Shirokov AA, Navolokin NV. Blood-brain barrier and laser technology for drug brain delivery. J Innov Opt Health Sciences. 2017;10(5):1730011.","DOI":"10.1142\/S1793545817300117"},{"key":"1389_CR31","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrn2038","volume":"8","author":"ML Block","year":"2007","unstructured":"Block ML, Zecca L, Hong J-S. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007;8:57\u201369.","journal-title":"Nat Rev Neurosci"},{"key":"1389_CR32","doi-asserted-by":"publisher","first-page":"370526","DOI":"10.1155\/2013\/370526","volume":"2013","author":"YC Chung","year":"2013","unstructured":"Chung YC, Kim Y-S, Bok E, Yune TY, Maeng S, Jin BK. MMP-3 contributes to nigrostriatal dopaminergic neuronal loss, BBB damage, and neuroinflammation in an MPTP mouse model of Parkinson\u2019s disease. Mediat Inflamm. 2013;2013:370526.","journal-title":"Mediat Inflamm"},{"key":"1389_CR33","doi-asserted-by":"publisher","first-page":"E486","DOI":"10.1016\/S1470-2045(15)00141-2","volume":"16","author":"T Ajithkumar","year":"2015","unstructured":"Ajithkumar T, Parkinson C, Fife K, Corrie P, Jeff S. Evolving treatment options for melanoma brain metastases. Lancet Oncol. 2015;16:E486\u201397.","journal-title":"Lancet Oncol"},{"key":"1389_CR34","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1016\/S0140-6736(12)60398-5","volume":"379","author":"GS Falchook","year":"2012","unstructured":"Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau TH, Brown MP, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet. 2012;379:1893\u2013901.","journal-title":"Lancet"},{"key":"1389_CR35","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1038\/nn1472","volume":"8","author":"D Davalos","year":"2005","unstructured":"Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005;8:752\u20138.","journal-title":"Nat Neurosci"},{"key":"1389_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11499","volume":"7","author":"G Szalay","year":"2016","unstructured":"Szalay G, Martinecz B, L\u00e9n\u00e1rt N, K\u00f6rnyei Z, Orsolits B, Jud\u00e1k L, et al. Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke. Nat Commun. 2016;7:11499.","journal-title":"Nat Commun"},{"key":"1389_CR37","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s10585-013-9566-9","volume":"30","author":"I Daphu","year":"2013","unstructured":"Daphu I, Sundstr\u00f8m T, Horn S, Huszthy PC, Niclou SP, Sakariassen P\u00d8, et al. In vivo animal models for studying brain metastasis: value and limitations. Clin Exp Metastasis. 2013;30:695\u2013710.","journal-title":"Clin Exp Metastasis"},{"key":"1389_CR38","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1111\/cas.12600","volume":"106","author":"S Nanjo","year":"2015","unstructured":"Nanjo S, Nakagawa T, Takeuchi S, Kita K, Fukuda K, Nakada M, et al. In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line. Cancer Sci. 2015;106:244\u201352.","journal-title":"Cancer Sci"},{"key":"1389_CR39","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/aps.2016.107","volume":"38","author":"S-R Zhang","year":"2017","unstructured":"Zhang S-R, Zhu L-C, Jiang Y-P, Zhang J, Xu R-J, Xu Y-S, et al. Efficacy of afatinib, an irreversible ErbB family blocker, in the treatment of intracerebral metastases of non-small cell lung cancer in mice. Acta Pharmacol Sin. 2017;38:233\u201340.","journal-title":"Acta Pharmacol Sin"},{"key":"1389_CR40","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1002\/ijc.2910440524","volume":"44","author":"G Schackert","year":"1989","unstructured":"Schackert G, Price JE, Bucana CD, Fidler IJ. Unique patterns of brain metastasis produced by different human carcinomas in athymic nude mice. Int J Cancer. 1989;44:892\u20137.","journal-title":"Int J Cancer"},{"key":"1389_CR41","first-page":"3478","volume":"48","author":"G Schackert","year":"1988","unstructured":"Schackert G, Fidler IJ. Site-specific metastasis of mouse melanomas and a fibrosarcoma in the brain or meninges of syngeneic animals. Cancer Res. 1988;48:3478\u201384.","journal-title":"Cancer Res"},{"key":"1389_CR42","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.7150\/thno.14145","volume":"6","author":"F Yang","year":"2016","unstructured":"Yang F, Liu S, Liu X, Liu L, Luo M, Qi S, et al. In vivo visualization of tumor antigen-containing microparticles generated in fluorescent-protein-elicited immunity. Theranostics. 2016;6:1453\u201366.","journal-title":"Theranostics"},{"key":"1389_CR43","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1101\/pdb.prot069617","volume":"2012","author":"A Holtmaat","year":"2012","unstructured":"Holtmaat A, de Paola V, Wilbrecht L, Trachtenberg JT, Svoboda K, Portera-Cailliau C. Imaging neocortical neurons through a chronic cranial window. Cold Spring Harb Protoc. 2012;2012:694\u2013701.","journal-title":"Cold Spring Harb Protoc"},{"key":"1389_CR44","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.neuron.2014.02.040","volume":"82","author":"MRP Elmore","year":"2014","unstructured":"Elmore MRP, Najafi AR, Koike MA, Dagher NN, Spangenberg EE, Rice RA, et al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron. 2014;82:380\u201397.","journal-title":"Neuron"},{"key":"1389_CR45","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1021\/tx500046k","volume":"27","author":"V Singh","year":"2014","unstructured":"Singh V, Mitra S, Sharma AK, Gera R, Ghosh D. Isolation and characterization of microglia from adult mouse brain: selected applications for ex vivo evaluation of immunotoxicological alterations following in vivo xenobiotic exposure. Chem Res Toxicol. 2014;27:895\u2013903.","journal-title":"Chem Res Toxicol"},{"key":"1389_CR46","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1161\/01.CIR.0000014686.73212.DA","volume":"105","author":"AL Chancey","year":"2002","unstructured":"Chancey AL, Brower GL, Peterson JT, Janicki JS. Effects of matrix metalloproteinase inhibition on ventricular remodeling due to volume overload. Circulation. 2002;105:1983\u20138.","journal-title":"Circulation"},{"key":"1389_CR47","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.neuron.2010.09.043","volume":"68","author":"RD Bell","year":"2010","unstructured":"Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010;68:409\u201327.","journal-title":"Neuron"},{"key":"1389_CR48","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1038\/nn1805","volume":"9","author":"SE Haynes","year":"2006","unstructured":"Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan W-B, et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci. 2006;9:1512\u20139.","journal-title":"Nat Neurosci"},{"key":"1389_CR49","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.joca.2016.09.007","volume":"25","author":"PB Tran","year":"2017","unstructured":"Tran PB, Miller RE, Ishihara S, Miller RJ, Malfait AM. Spinal microglial activation in a murine surgical model of knee osteoarthritis. Osteoarthr Cartil. 2017;25:718\u201326.","journal-title":"Osteoarthr Cartil"},{"key":"1389_CR50","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1002\/glia.10149","volume":"40","author":"Y Imai","year":"2002","unstructured":"Imai Y, Kohsaka S. Intracellular signaling in M-CSF-induced microglia activation: role of Iba1. Glia. 2002;40:164\u201374.","journal-title":"Glia"},{"key":"1389_CR51","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;19:987\u201391.","journal-title":"Nat Neurosci"},{"key":"1389_CR52","first-page":"3160","volume":"5","author":"S Qi","year":"2016","unstructured":"Qi S, Li H, Lu L, Qi Z, Liu L, Chen L, et al. Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy. Elife. 2016;5:3160.","journal-title":"Elife"},{"key":"1389_CR53","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1038\/nri2638","volume":"9","author":"JB Beltman","year":"2009","unstructured":"Beltman JB, Mar\u00e9e AFM, de Boer RJ. Analysing immune cell migration. Nat Rev Immunol. 2009;9:789\u201398.","journal-title":"Nat Rev Immunol"},{"key":"1389_CR54","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/nn.4132","volume":"18","author":"H Asai","year":"2015","unstructured":"Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015;18:1584\u201393.","journal-title":"Nat Neurosci"},{"key":"1389_CR55","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nrclinonc.2011.58","volume":"8","author":"AF Eichler","year":"2011","unstructured":"Eichler AF, Chung E, Kodack DP, Loeffler JS, Fukumura D, Jain RK. The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol. 2011;8:344\u201356.","journal-title":"Nat Rev Clin Oncol"},{"key":"1389_CR56","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.semcancer.2010.12.009","volume":"21","author":"IJ Fidler","year":"2011","unstructured":"Fidler IJ. The role of the organ microenvironment in brain metastasis. Semin Cancer Biol. 2011;21:107\u201312.","journal-title":"Semin Cancer Biol"},{"key":"1389_CR57","doi-asserted-by":"publisher","first-page":"6716","DOI":"10.1038\/ncomms7716","volume":"6","author":"N Tominaga","year":"2015","unstructured":"Tominaga N, Kosaka N, Ono M, Katsuda T, Yoshioka Y, Tamura K, et al. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat Commun. 2015;6:6716.","journal-title":"Nat Commun"},{"key":"1389_CR58","doi-asserted-by":"publisher","first-page":"9842","DOI":"10.1074\/jbc.M114.602185","volume":"290","author":"K Wu","year":"2015","unstructured":"Wu K, Fukuda K, Xing F, Zhang Y, Sharma S, Liu Y, et al. Roles of the cyclooxygenase 2 matrix metalloproteinase 1 pathway in brain metastasis of breast cancer. J Biol Chem. 2015;290:9842\u201354.","journal-title":"J Biol Chem"},{"key":"1389_CR59","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s10549-014-2854-5","volume":"144","author":"J Do","year":"2014","unstructured":"Do J, Foster D, Renier C, Vogel H, Rosenblum S, Doyle TC, et al. Ex vivo Evans blue assessment of the blood brain barrier in three breast cancer brain metastasis models. Breast Cancer Res Treat. 2014;144:93\u2013101.","journal-title":"Breast Cancer Res Treat"},{"key":"1389_CR60","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0166-2236(97)01169-7","volume":"21","author":"VW Yong","year":"1998","unstructured":"Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR. Matrix metalloproteinases and diseases of the CNS. Trends Neurosci. 1998;21:75\u201380.","journal-title":"Trends Neurosci"},{"key":"1389_CR61","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","volume":"141","author":"B-Z Qian","year":"2010","unstructured":"Qian B-Z, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141:39\u201351.","journal-title":"Cell"},{"key":"1389_CR62","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.it.2015.02.004","volume":"36","author":"R Ostuni","year":"2015","unstructured":"Ostuni R, Kratochvill F, Murray PJ, Natoli G. Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol. 2015;36:229\u201339.","journal-title":"Trends Immunol"},{"key":"1389_CR63","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s00401-015-1529-6","volume":"131","author":"S Brandenburg","year":"2016","unstructured":"Brandenburg S, M\u00fcller A, Turkowski K, Radev YT, Rot S, Schmidt C, et al. Resident microglia rather than peripheral macrophages promote vascularization in brain tumors and are source of alternative pro-angiogenic factors. Acta Neuropathol. 2016;131:365\u201378.","journal-title":"Acta Neuropathol"},{"key":"1389_CR64","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1126\/science.1227901","volume":"339","author":"A Aguzzi","year":"2013","unstructured":"Aguzzi A, Barres BA, Bennett ML. Microglia: scapegoat, saboteur, or something else? Science. 2013;339:156\u201361.","journal-title":"Science"},{"key":"1389_CR65","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nri3175","volume":"12","author":"DI Gabrilovich","year":"2012","unstructured":"Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12:253\u201368.","journal-title":"Nat Rev Immunol"},{"key":"1389_CR66","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.biomaterials.2016.05.008","volume":"98","author":"Y Qian","year":"2016","unstructured":"Qian Y, Jin H, Qiao S, Dai Y, Huang C, Lu L, et al. Targeting dendritic cells in lymph node with an antigen peptide-based nanovaccine for cancer immunotherapy. Biomaterials. 2016;98:171\u201383.","journal-title":"Biomaterials"},{"key":"1389_CR67","doi-asserted-by":"publisher","first-page":"9171","DOI":"10.1002\/anie.200903112","volume":"48","author":"Z Zhang","year":"2009","unstructured":"Zhang Z, Cao W, Jin H, Lovell JF, Yang M, Ding L, et al. Biomimetic nanocarrier for direct cytosolic drug delivery. Angew Chem Int Ed Engl. 2009;48:9171\u20135.","journal-title":"Angew Chem Int Ed Engl"},{"key":"1389_CR68","doi-asserted-by":"publisher","first-page":"9536","DOI":"10.1021\/acsnano.7b05465","volume":"11","author":"Y Qian","year":"2017","unstructured":"Qian Y, Qiao S, Dai Y, Xu G, Dai B, Lu L, et al. Molecular-targeted immunotherapeutic strategy for melanoma via dual-targeting nanoparticles delivering small interfering RNA to tumor-associated macrophages. ACS Nano. 2017;11:9536\u201349.","journal-title":"ACS Nano"},{"key":"1389_CR69","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1096\/fj.06-5865com","volume":"21","author":"Y-S Kim","year":"2007","unstructured":"Kim Y-S, Choi DH, Block ML, Lorenzl S, Yang L, Kim YJ, et al. A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation. FASEB J. 2007;21:179\u201387.","journal-title":"FASEB J"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-018-1389-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12974-018-1389-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-018-1389-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T19:17:02Z","timestamp":1578338222000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-018-1389-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,7]]},"references-count":69,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1389"],"URL":"https:\/\/doi.org\/10.1186\/s12974-018-1389-9","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,7]]},"assertion":[{"value":"28 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal studies were conducted in compliance with protocols approved by the Hubei Provincial Animal Care and Use Committee and in compliance with the experimental guidelines of the Animal Experimentation Ethics Committee of Huazhong University of Science and Technology.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"4"}}