{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:37:25Z","timestamp":1787020645319,"version":"build-2736575974"},"reference-count":125,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:00:00Z","timestamp":1602028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RTG 1715"],"award-info":[{"award-number":["RTG 1715"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RTG 1715"],"award-info":[{"award-number":["RTG 1715"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["RTG 1715"],"award-info":[{"award-number":["RTG 1715"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND","award":["609020-Scientia Fellows"],"award-info":[{"award-number":["609020-Scientia Fellows"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Sepsis-associated encephalopathy (SAE) is an early and frequent event of infection-induced systemic inflammatory response syndrome. Phosphoinositide 3-kinase \u03b3 (PI3K\u03b3) is linked to neuroinflammation and inflammation-related microglial activity. In homeotherms, variations in ambient temperature (T\n                      <jats:sub>a<\/jats:sub>\n                      ) outside the thermoneutral zone lead to thermoregulatory responses, mainly driven by a gradually increasing sympathetic activity, and may affect disease severity. We hypothesized that thermoregulatory response to hypothermia (reduced T\n                      <jats:sub>a<\/jats:sub>\n                      ) aggravates SAE in PI3K\u03b3-dependent manner.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Experiments were performed in wild-type, PI3K\u03b3 knockout, and PI3K\u03b3 kinase-dead mice, which were kept at neutral (30 \u00b1 0.5\u2009\u00b0C) or moderately lowered (26 \u00b1 0.5\u2009\u00b0C) T\n                      <jats:sub>a<\/jats:sub>\n                      . Mice were exposed to lipopolysaccharide (LPS, 10\u2009\u03bcg\/g, from\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      serotype 055:B5, single intraperitoneal injection)\u2014evoked systemic inflammatory response (SIR) and monitored 24\u2009h for thermoregulatory response and blood\u2013brain barrier integrity. Primary microglial cells and brain tissue derived from treated mice were analyzed for inflammatory responses and related cell functions. Comparisons between groups were made with one-way or two-way analysis of variance, as appropriate. Post hoc comparisons were made with the Holm\u2013Sidak test or\n                      <jats:italic>t<\/jats:italic>\n                      tests with Bonferroni\u2019s correction for adjustments of multiple comparisons. Data not following normal distribution was tested with Kruskal-Wallis test followed by Dunn\u2019s multiple comparisons test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that a moderate reduction of ambient temperature triggers enhanced hypothermia of mice undergoing LPS-induced systemic inflammation by aggravated SAE. PI3K\u03b3 deficiency enhances blood\u2013brain barrier injury and upregulation of matrix metalloproteinases (MMPs) as well as an impaired microglial phagocytic activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Thermoregulatory adaptation in response to ambient temperatures below the thermoneutral range exacerbates LPS-induced blood\u2013brain barrier injury and neuroinflammation. PI3K\u03b3 serves a protective role in suppressing release of MMPs, maintaining microglial motility and reinforcing phagocytosis leading to improved brain tissue integrity. Thus, preclinical research targeting severe brain inflammation responses is seriously biased when basic physiological prerequisites of mammal species such as preferred ambient temperature are ignored.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-020-01954-7","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:05:50Z","timestamp":1602029150000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Impact of ambient temperature on inflammation-induced encephalopathy in endotoxemic mice\u2014role of phosphoinositide 3-kinase gamma"],"prefix":"10.1186","volume":"17","author":[{"given":"Guang-Ping","family":"Lang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadin","family":"Ndongson-Dongmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trim","family":"Lajqi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brodhun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Wetzker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Frasch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4294-3758","authenticated-orcid":false,"given":"Reinhard","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,7]]},"reference":[{"key":"1954_CR1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1080\/14787210.2017.1265448","volume":"15","author":"SC Tauber","year":"2017","unstructured":"Tauber SC, Eiffert H, Bruck W, Nau R. Septic encephalopathy and septic encephalitis. Expert Rev Anti Infect Ther. 2017;15:121\u201332.","journal-title":"Expert Rev Anti Infect Ther"},{"key":"1954_CR2","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nrneurol.2012.183","volume":"8","author":"TE Gofton","year":"2012","unstructured":"Gofton TE, Young GB. Sepsis-associated encephalopathy. Nat Rev Neurol. 2012;8:557\u201366.","journal-title":"Nat Rev Neurol"},{"key":"1954_CR3","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/S2213-2600(14)70246-2","volume":"3","author":"D Annane","year":"2015","unstructured":"Annane D, Sharshar T. Cognitive decline after sepsis. Lancet Respir Med. 2015;3:61\u20139.","journal-title":"Lancet Respir Med"},{"key":"1954_CR4","doi-asserted-by":"publisher","first-page":"597","DOI":"10.3389\/fimmu.2017.00597","volume":"8","author":"SJ Kuperberg","year":"2017","unstructured":"Kuperberg SJ, Wadgaonkar R. Sepsis-associated encephalopathy: the blood-brain barrier and the sphingolipid rheostat. Front Immunol. 2017;8:597.","journal-title":"Front Immunol"},{"key":"1954_CR5","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1007\/s12017-014-8320-z","volume":"16","author":"A Frister","year":"2014","unstructured":"Frister A, Schmidt C, Schneble N, Brodhun M, Gonnert FA, Bauer M, Hirsch E, Muller JP, Wetzker R, Bauer R. Phosphoinositide 3-kinase gamma affects LPS-induced disturbance of blood-brain barrier via lipid kinase-independent control of cAMP in microglial cells. Neuromolecular Med. 2014;16:704\u201313.","journal-title":"Neuromolecular Med"},{"key":"1954_CR6","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.cell.2019.08.053","volume":"179","author":"M Prinz","year":"2019","unstructured":"Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts. Cell. 2019;179:292\u2013311.","journal-title":"Cell"},{"key":"1954_CR7","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41586-018-0023-4","volume":"556","author":"AC Wendeln","year":"2018","unstructured":"Wendeln AC, Degenhardt K, Kaurani L, Gertig M, Ulas T, Jain G, Wagner J, Hasler LM, Wild K, Skodras A, et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature. 2018;556:332\u20138.","journal-title":"Nature"},{"key":"1954_CR8","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.3389\/fimmu.2019.02492","volume":"10","author":"T Lajqi","year":"2019","unstructured":"Lajqi T, Lang GP, Haas F, Williams DL, Hudalla H, Bauer M, Groth M, Wetzker R, Bauer R. Memory-like inflammatory responses of microglia to rising doses of LPS: key role of PI3Kgamma. Front Immunol. 2019;10:2492.","journal-title":"Front Immunol"},{"key":"1954_CR9","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.cellimm.2018.01.004","volume":"330","author":"D Low","year":"2018","unstructured":"Low D, Ginhoux F. Recent advances in the understanding of microglial development and homeostasis. Cell Immunol. 2018;330:68\u201378.","journal-title":"Cell Immunol"},{"key":"1954_CR10","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1113\/JP272134","volume":"595","author":"TL Tay","year":"2017","unstructured":"Tay TL, Savage JC, Hui CW, Bisht K, Tremblay ME. Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. J Physiol. 2017;595:1929\u201345.","journal-title":"J Physiol"},{"key":"1954_CR11","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":"1954_CR12","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1038\/nn1997","volume":"10","author":"UK Hanisch","year":"2007","unstructured":"Hanisch UK, 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":"1954_CR13","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1038\/nm.4397","volume":"23","author":"MW Salter","year":"2017","unstructured":"Salter MW, Stevens B. Microglia emerge as central players in brain disease. Nat Med. 2017;23:1018\u201327.","journal-title":"Nat Med"},{"key":"1954_CR14","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1152\/physrev.00011.2010","volume":"91","author":"H Kettenmann","year":"2011","unstructured":"Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91:461\u2013553.","journal-title":"Physiol Rev"},{"key":"1954_CR15","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nature09615","volume":"468","author":"RM Ransohoff","year":"2010","unstructured":"Ransohoff RM, Cardona AE. The myeloid cells of the central nervous system parenchyma. Nature. 2010;468:253\u201362.","journal-title":"Nature"},{"key":"1954_CR16","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, Littman DR, Dustin ML, Gan WB. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005;8:752\u20138.","journal-title":"Nat Neurosci"},{"key":"1954_CR17","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/scientificamerican1195-54","volume":"273","author":"WJ Streit","year":"1995","unstructured":"Streit WJ, Kincaid-Colton CA. The brain\u2019s immune system. Sci Am. 1995;273:54\u20135 58-61.","journal-title":"Sci Am"},{"key":"1954_CR18","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 HW, Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol. 2017;79:619\u201343.","journal-title":"Annu Rev Physiol"},{"key":"1954_CR19","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":"1954_CR20","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3389\/fncel.2014.00101","volume":"8","author":"U Gertig","year":"2014","unstructured":"Gertig U, Hanisch UK. Microglial diversity by responses and responders. Front Cell Neurosci. 2014;8:101.","journal-title":"Front Cell Neurosci"},{"key":"1954_CR21","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1007\/s11481-013-9490-4","volume":"8","author":"BJ Eggen","year":"2013","unstructured":"Eggen BJ, Raj D, Hanisch UK, Boddeke HW. Microglial phenotype and adaptation. J Neuroimmune Pharmacol. 2013;8:807\u201323.","journal-title":"J Neuroimmune Pharmacol"},{"key":"1954_CR22","doi-asserted-by":"publisher","first-page":"R1207","DOI":"10.1152\/ajpregu.00109.2011","volume":"301","author":"K Nakamura","year":"2011","unstructured":"Nakamura K. Central circuitries for body temperature regulation and fever. Am J Physiol Regul Integr Comp Physiol. 2011;301:R1207\u201328.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1954_CR23","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s00424-017-2090-z","volume":"470","author":"Y Nakamura","year":"2018","unstructured":"Nakamura Y, Nakamura K. Central regulation of brown adipose tissue thermogenesis and energy homeostasis dependent on food availability. Pflugers Arch. 2018;470:823\u201337.","journal-title":"Pflugers Arch"},{"key":"1954_CR24","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1097\/00003246-199210000-00006","volume":"20","author":"TP Clemmer","year":"1992","unstructured":"Clemmer TP, Fisher CJ Jr, Bone RC, Slotman GJ, Metz CA, Thomas FO. Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group. Crit Care Med. 1992;20:1395\u2013401.","journal-title":"Crit Care Med"},{"key":"1954_CR25","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s00134-012-2478-3","volume":"38","author":"PJ Young","year":"2012","unstructured":"Young PJ, Saxena M, Beasley R, Bellomo R, Bailey M, Pilcher D, Finfer S, Harrison D, Myburgh J, Rowan K. Early peak temperature and mortality in critically ill patients with or without infection. Intensive Care Med. 2012;38:437\u201344.","journal-title":"Intensive Care Med"},{"key":"1954_CR26","first-page":"1254","volume":"78","author":"F Schortgen","year":"2012","unstructured":"Schortgen F. Fever in sepsis. Minerva Anestesiol. 2012;78:1254\u201364.","journal-title":"Minerva Anestesiol"},{"key":"1954_CR27","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1097\/00005373-200103000-00016","volume":"50","author":"J Cumming","year":"2001","unstructured":"Cumming J, Purdue GF, Hunt JL, O'Keefe GE. Objective estimates of the incidence and consequences of multiple organ dysfunction and sepsis after burn trauma. J Trauma. 2001;50:510\u20135.","journal-title":"J Trauma"},{"key":"1954_CR28","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.injury.2012.12.027","volume":"45","author":"K Soreide","year":"2014","unstructured":"Soreide K. Clinical and translational aspects of hypothermia in major trauma patients: from pathophysiology to prevention, prognosis and potential preservation. Injury. 2014;45:647\u201354.","journal-title":"Injury"},{"issue":"Suppl 2","key":"1954_CR29","doi-asserted-by":"publisher","first-page":"S53","DOI":"10.1038\/ijo.2010.240","volume":"34","author":"JM Overton","year":"2010","unstructured":"Overton JM. Phenotyping small animals as models for the human metabolic syndrome: thermoneutrality matters. Int J Obes (Lond). 2010;34(Suppl 2):S53\u20138.","journal-title":"Int J Obes (Lond)"},{"key":"1954_CR30","unstructured":"EP. C: Directive 2010\/63\/EU of the European Parliament and of the council on the protection of animals used for scientific purposes. . Off J Euro Union L 2010, 276:33\u201379."},{"key":"1954_CR31","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1126\/science.287.5455.1049","volume":"287","author":"E Hirsch","year":"2000","unstructured":"Hirsch E, Katanaev VL, Garlanda C, Azzolino O, Pirola L, Silengo L, Sozzani S, Mantovani A, Altruda F, Wymann MP. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science. 2000;287:1049\u201353.","journal-title":"Science"},{"key":"1954_CR32","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.cell.2004.07.017","volume":"118","author":"E Patrucco","year":"2004","unstructured":"Patrucco E, Notte A, Barberis L, Selvetella G, Maffei A, Brancaccio M, Marengo S, Russo G, Azzolino O, Rybalkin SD, et al. PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Cell. 2004;118:375\u201387.","journal-title":"Cell"},{"key":"1954_CR33","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1093\/ilar.47.4.364","volume":"47","author":"JA Obernier","year":"2006","unstructured":"Obernier JA, Baldwin RL. Establishing an appropriate period of acclimatization following transportation of laboratory animals. ILAR J. 2006;47:364\u20139.","journal-title":"ILAR J"},{"key":"1954_CR34","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S0031-9384(98)00148-6","volume":"65","author":"CJ Gordon","year":"1998","unstructured":"Gordon CJ, Becker P, Ali JS. Behavioral thermoregulatory responses of single- and group-housed mice. Physiol Behav. 1998;65:255\u201362.","journal-title":"Physiol Behav"},{"key":"1954_CR35","doi-asserted-by":"publisher","first-page":"e123","DOI":"10.1016\/j.jss.2011.05.019","volume":"170","author":"FA Gonnert","year":"2011","unstructured":"Gonnert FA, Recknagel P, Seidel M, Jbeily N, Dahlke K, Bockmeyer CL, Winning J, Losche W, Claus RA, Bauer M. Characteristics of clinical sepsis reflected in a reliable and reproducible rodent sepsis model. J Surg Res. 2011;170:e123\u201334.","journal-title":"J Surg Res"},{"key":"1954_CR36","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s00134-011-2151-2","volume":"37","author":"CM Comim","year":"2011","unstructured":"Comim CM, Vilela MC, Constantino LS, Petronilho F, Vuolo F, Lacerda-Queiroz N, Rodrigues DH, da Rocha JL, Teixeira AL, Quevedo J, Dal-Pizzol F. Traffic of leukocytes and cytokine up-regulation in the central nervous system in sepsis. Intensive Care Med. 2011;37:711\u20138.","journal-title":"Intensive Care Med"},{"key":"1954_CR37","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1523\/JNEUROSCI.06-08-02163.1986","volume":"6","author":"D Giulian","year":"1986","unstructured":"Giulian D, Baker TJ. Characterization of ameboid microglia isolated from developing mammalian brain. J Neurosci. 1986;6:2163\u201378.","journal-title":"J Neurosci"},{"key":"1954_CR38","doi-asserted-by":"crossref","unstructured":"Lian H, Roy E, Zheng H. Protocol for primary microglial culture preparation. Bio Protoc. 2016;6.","DOI":"10.21769\/BioProtoc.1989"},{"key":"1954_CR39","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402\u20138.","journal-title":"Methods"},{"key":"1954_CR40","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1002\/glia.23100","volume":"65","author":"N Schneble","year":"2017","unstructured":"Schneble N, Muller J, Kliche S, Bauer R, Wetzker R, Bohmer FD, Wang ZQ, Muller JP. The protein-tyrosine phosphatase DEP-1 promotes migration and phagocytic activity of microglial cells in part through negative regulation of fyn tyrosine kinase. Glia. 2017;65:416\u201328.","journal-title":"Glia"},{"key":"1954_CR41","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/1742-2094-9-164","volume":"9","author":"JW Seo","year":"2012","unstructured":"Seo JW, Kim JH, Kim JH, Seo M, Han HS, Park J, Suk K. Time-dependent effects of hypothermia on microglial activation and migration. J Neuroinflammation. 2012;9:164.","journal-title":"J Neuroinflammation"},{"key":"1954_CR42","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.3382\/ps.2007-00202","volume":"87","author":"SF Sun","year":"2008","unstructured":"Sun SF, Pan QZ, Hui X, Zhang BL, Wu HM, Li H, Xu W, Zhang Q, Li JY, Deng XM, et al. Stronger in vitro phagocytosis by monocytes-macrophages is indicative of greater pathogen clearance and antibody levels in vivo. Poult Sci. 2008;87:1725\u201333.","journal-title":"Poult Sci"},{"key":"1954_CR43","volume-title":"The mouse brain in stereotaxic coordinates","author":"G Paxinos","year":"2001","unstructured":"Paxinos G, Franklin KBJ. The mouse brain in stereotaxic coordinates. San Diego: Academic Press; 2001."},{"key":"1954_CR44","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1007\/s004010000290","volume":"101","author":"M Brodhun","year":"2001","unstructured":"Brodhun M, Fritz H, Walter B, Antonow-Schlorke I, Reinhart K, Zwiener U, Bauer R, Patt S. Immunomorphological sequelae of severe brain injury induced by fluid-percussion in juvenile pigs--effects of mild hypothermia. Acta Neuropathol. 2001;101:424\u201334.","journal-title":"Acta Neuropathol"},{"key":"1954_CR45","first-page":"15","volume":"4","author":"F Zhang","year":"2008","unstructured":"Zhang F, Vadakkan KI, Kim SS, Wu LJ, Shang Y, Zhuo M. Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse. Mol Pain. 2008;4:15.","journal-title":"Mol Pain"},{"key":"1954_CR46","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0149-7634(05)80098-3","volume":"15","author":"CJ Gordon","year":"1991","unstructured":"Gordon CJ. Toxic-induced hypothermia and hypometabolism: do they increase uncertainty in the extrapolation of toxicological data from experimental animals to humans? Neurosci Biobehav Rev. 1991;15:95\u20138.","journal-title":"Neurosci Biobehav Rev"},{"key":"1954_CR47","volume-title":"Council of the National Academy of Science. Volume 8th ed. Nat. Res","author":"NRC: Guide for the care and use of laboratory animals","year":"2011","unstructured":"NRC: Guide for the care and use of laboratory animals. Council of the National Academy of Science. Volume 8th ed. Nat. Res. Washington,DC: The National Academy Press; 2011."},{"key":"1954_CR48","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1097\/SHK.0000000000001243","volume":"51","author":"B Zingarelli","year":"2019","unstructured":"Zingarelli B, Coopersmith CM, Drechsler S, Efron P, Marshall JC, Moldawer L, Wiersinga WJ, Xiao X, Osuchowski MF, Thiemermann C. Part I: minimum quality threshold in preclinical sepsis studies (MQTiPSS) for study design and humane modeling endpoints. Shock. 2019;51:10\u201322.","journal-title":"Shock"},{"key":"1954_CR49","doi-asserted-by":"publisher","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, Flecknell P, Gallagher L, Gibson CL, Haley MJ, 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":"1954_CR50","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/nrneurol.2013.232","volume":"10","author":"DW Howells","year":"2014","unstructured":"Howells DW, Sena ES, Macleod MR. Bringing rigour to translational medicine. Nat Rev Neurol. 2014;10:37\u201343.","journal-title":"Nat Rev Neurol"},{"key":"1954_CR51","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1161\/STROKEAHA.116.013643","volume":"47","author":"F Vahidy","year":"2016","unstructured":"Vahidy F, Schabitz WR, Fisher M, Aronowski J. Reporting standards for preclinical studies of stroke therapy. Stroke. 2016;47:2435\u20138.","journal-title":"Stroke"},{"key":"1954_CR52","doi-asserted-by":"publisher","first-page":"425","DOI":"10.30802\/AALAS-CM-18-000049","volume":"68","author":"FC Hankenson","year":"2018","unstructured":"Hankenson FC, Marx JO, Gordon CJ, David JM. Effects of rodent thermoregulation on animal models in the research environment. Comp Med. 2018;68:425\u201338.","journal-title":"Comp Med"},{"key":"1954_CR53","doi-asserted-by":"publisher","first-page":"631","DOI":"10.4049\/jimmunol.1800621","volume":"202","author":"BL Hylander","year":"2019","unstructured":"Hylander BL, Gordon CJ, Repasky EA. Manipulation of ambient housing temperature to study the impact of chronic stress on immunity and cancer in mice. J Immunol. 2019;202:631\u20136.","journal-title":"J Immunol"},{"key":"1954_CR54","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s40635-015-0048-z","volume":"3","author":"S Drechsler","year":"2015","unstructured":"Drechsler S, Weixelbaumer KM, Weidinger A, Raeven P, Khadem A, Redl H, van Griensven M, Bahrami S, Remick D, Kozlov A, Osuchowski MF. Why do they die? Comparison of selected aspects of organ injury and dysfunction in mice surviving and dying in acute abdominal sepsis. Intensive Care Med Exp. 2015;3:48.","journal-title":"Intensive Care Med Exp"},{"key":"1954_CR55","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1097\/SHK.0000000000001007","volume":"50","author":"O Laitano","year":"2018","unstructured":"Laitano O, Van Steenbergen D, Mattingly AJ, Garcia CK, Robinson GP, Murray KO, Clanton TL, Nunamaker EA. Xiphoid surface temperature predicts mortality in a murine model of septic shock. Shock. 2018;50:226\u201332.","journal-title":"Shock"},{"key":"1954_CR56","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.jss.2012.05.078","volume":"181","author":"P Miao","year":"2013","unstructured":"Miao P, Kong Y, Ma Y, Zeng H, Yu Z. Hypothermia predicts the prognosis in colon ascendens stent peritonitis mice. J Surg Res. 2013;181:129\u201335.","journal-title":"J Surg Res"},{"key":"1954_CR57","first-page":"S67","volume":"43","author":"P Rothe","year":"2015","unstructured":"Rothe P, Sommerfeld O, Queissner CH, Otto GP, Sossdorf M, Richter A, Claus RA. Continuous non-invasive infrared monitoring in animal research during infectious diseases. Infection. 2015;43:S67\u20138.","journal-title":"Infection"},{"key":"1954_CR58","first-page":"492","volume":"61","author":"RA Trammell","year":"2011","unstructured":"Trammell RA, Toth LA. Markers for predicting death as an outcome for mice used in infectious disease research. Comp Med. 2011;61:492\u20138.","journal-title":"Comp Med"},{"key":"1954_CR59","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1093\/qjmed\/95.12.775","volume":"95","author":"ML Mallet","year":"2002","unstructured":"Mallet ML. Pathophysiology of accidental hypothermia. QJM. 2002;95:775\u201385.","journal-title":"QJM"},{"key":"1954_CR60","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s00395-019-0734-1","volume":"114","author":"B Ndongson-Dongmo","year":"2019","unstructured":"Ndongson-Dongmo B, Lang GP, Mece O, Hechaichi N, Lajqi T, Hoyer D, Brodhun M, Heller R, Wetzker R, Franz M, et al. Reduced ambient temperature exacerbates SIRS-induced cardiac autonomic dysregulation and myocardial dysfunction in mice. Basic Res Cardiol. 2019;114:26.","journal-title":"Basic Res Cardiol"},{"key":"1954_CR61","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.physbeh.2017.05.026","volume":"179","author":"CJ Gordon","year":"2017","unstructured":"Gordon CJ. The mouse thermoregulatory system: its impact on translating biomedical data to humans. Physiol Behav. 2017;179:55\u201366.","journal-title":"Physiol Behav"},{"key":"1954_CR62","first-page":"R693","volume":"270","author":"AA Romanovsky","year":"1996","unstructured":"Romanovsky AA, Shido O, Sakurada S, Sugimoto N, Nagasaka T. Endotoxin shock: thermoregulatory mechanisms. Am J Physiol. 1996;270:R693\u2013703.","journal-title":"Am J Physiol"},{"key":"1954_CR63","doi-asserted-by":"publisher","first-page":"R1244","DOI":"10.1152\/ajpregu.00370.2005","volume":"289","author":"AY Rudaya","year":"2005","unstructured":"Rudaya AY, Steiner AA, Robbins JR, Dragic AS, Romanovsky AA. Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the dose and ambient temperature. Am J Physiol Regul Integr Comp Physiol. 2005;289:R1244\u201352.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1954_CR64","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/2052-0492-2-14","volume":"2","author":"S Kushimoto","year":"2014","unstructured":"Kushimoto S, Yamanouchi S, Endo T, Sato T, Nomura R, Fujita M, Kudo D, Omura T, Miyagawa N, Sato T. Body temperature abnormalities in non-neurological critically ill patients: a review of the literature. J Intensive Care. 2014;2:14.","journal-title":"J Intensive Care"},{"key":"1954_CR65","doi-asserted-by":"crossref","unstructured":"Romanovsky AA, Shido O, Sakurada S, Sugimoto N, Nagasaka T: Endotoxin shock-associated hypothermia. How and why does it occur? Ann N Y Acad Sci 1997, 813:733-737.","DOI":"10.1111\/j.1749-6632.1997.tb51775.x"},{"key":"1954_CR66","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.2741\/1381","volume":"9","author":"LR Leon","year":"2004","unstructured":"Leon LR. Hypothermia in systemic inflammation: role of cytokines. Front Biosci. 2004;9:1877\u201388.","journal-title":"Front Biosci"},{"key":"1954_CR67","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/0006-8993(95)01474-8","volume":"713","author":"CD Breder","year":"1996","unstructured":"Breder CD, Saper CB. Expression of inducible cyclooxygenase mRNA in the mouse brain after systemic administration of bacterial lipopolysaccharide. Brain Res. 1996;713:64\u20139.","journal-title":"Brain Res"},{"key":"1954_CR68","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1002\/(SICI)1096-9861(19970505)381:2<119::AID-CNE1>3.0.CO;2-6","volume":"381","author":"JK Elmquist","year":"1997","unstructured":"Elmquist JK, Breder CD, Sherin JE, Scammell TE, Hickey WF, Dewitt D, Saper CB. Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages. J Comp Neurol. 1997;381:119\u201329.","journal-title":"J Comp Neurol"},{"key":"1954_CR69","doi-asserted-by":"publisher","first-page":"8103","DOI":"10.4049\/jimmunol.177.11.8103","volume":"177","author":"H Zhou","year":"2006","unstructured":"Zhou H, Lapointe BM, Clark SR, Zbytnuik L, Kubes P. A requirement for microglial TLR4 in leukocyte recruitment into brain in response to lipopolysaccharide. J Immunol. 2006;177:8103\u201310.","journal-title":"J Immunol"},{"key":"1954_CR70","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.1523\/JNEUROSCI.21-08-02669.2001","volume":"21","author":"K Yamagata","year":"2001","unstructured":"Yamagata K, Matsumura K, Inoue W, Shiraki T, Suzuki K, Yasuda S, Sugiura H, Cao C, Watanabe Y, Kobayashi S. Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endothelial cells of rats during endotoxin-induced fever. J Neurosci. 2001;21:2669\u201377.","journal-title":"J Neurosci"},{"key":"1954_CR71","doi-asserted-by":"publisher","first-page":"6279","DOI":"10.1523\/JNEUROSCI.18-16-06279.1998","volume":"18","author":"K Matsumura","year":"1998","unstructured":"Matsumura K, Cao C, Ozaki M, Morii H, Nakadate K, Watanabe Y. Brain endothelial cells express cyclooxygenase-2 during lipopolysaccharide-induced fever: light and electron microscopic immunocytochemical studies. J Neurosci. 1998;18:6279\u201389.","journal-title":"J Neurosci"},{"key":"1954_CR72","first-page":"R1712","volume":"272","author":"C Cao","year":"1997","unstructured":"Cao C, Matsumura K, Yamagata K, Watanabe Y. Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain. Am J Physiol. 1997;272:R1712\u201325.","journal-title":"Am J Physiol"},{"key":"1954_CR73","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.bbi.2012.11.015","volume":"28","author":"H Al-Saffar","year":"2013","unstructured":"Al-Saffar H, Lewis K, Liu E, Schober A, Corrigan JJ, Shibata K, Steiner AA. Lipopolysaccharide-induced hypothermia and hypotension are associated with inflammatory signaling that is triggered outside the brain. Brain Behav Immun. 2013;28:188\u201395.","journal-title":"Brain Behav Immun"},{"key":"1954_CR74","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/B978-0-444-64074-1.00034-3","volume":"157","author":"A Garami","year":"2018","unstructured":"Garami A, Steiner AA, Romanovsky AA. Fever and hypothermia in systemic inflammation. Handb Clin Neurol. 2018;157:565\u201397.","journal-title":"Handb Clin Neurol"},{"key":"1954_CR75","doi-asserted-by":"publisher","first-page":"3901","DOI":"10.1113\/jphysiol.2014.277277","volume":"592","author":"JJ Corrigan","year":"2014","unstructured":"Corrigan JJ, Fonseca MT, Flatow EA, Lewis K, Steiner AA. Hypometabolism and hypothermia in the rat model of endotoxic shock: independence of circulatory hypoxia. J Physiol. 2014;592:3901\u201316.","journal-title":"J Physiol"},{"key":"1954_CR76","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1242\/jeb.050989","volume":"214","author":"B Cannon","year":"2011","unstructured":"Cannon B, Nedergaard J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol. 2011;214:242\u201353.","journal-title":"J Exp Biol"},{"key":"1954_CR77","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.bbi.2007.03.007","volume":"21","author":"KA Jhaveri","year":"2007","unstructured":"Jhaveri KA, Trammell RA, Toth LA. Effect of environmental temperature on sleep, locomotor activity, core body temperature and immune responses of C57BL\/6\u2009J mice. Brain Behav Immun. 2007;21:975\u201387.","journal-title":"Brain Behav Immun"},{"key":"1954_CR78","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.bbi.2013.11.017","volume":"36","author":"E Szentirmai","year":"2014","unstructured":"Szentirmai E, Krueger JM. Sickness behaviour after lipopolysaccharide treatment in ghrelin deficient mice. Brain Behav Immun. 2014;36:200\u20136.","journal-title":"Brain Behav Immun"},{"key":"1954_CR79","doi-asserted-by":"publisher","first-page":"26476","DOI":"10.1074\/jbc.M115.677724","volume":"290","author":"M Okla","year":"2015","unstructured":"Okla M, Wang W, Kang I, Pashaj A, Carr T, Chung S. Activation of Toll-like receptor 4 (TLR4) attenuates adaptive thermogenesis via endoplasmic reticulum stress. J Biol Chem. 2015;290:26476\u201390.","journal-title":"J Biol Chem"},{"key":"1954_CR80","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1038\/jcbfm.2011.197","volume":"32","author":"GA Rosenberg","year":"2012","unstructured":"Rosenberg GA. Neurological diseases in relation to the blood-brain barrier. J Cereb Blood Flow Metab. 2012;32:1139\u201351.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1954_CR81","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.neuroscience.2008.06.025","volume":"158","author":"E Candelario-Jalil","year":"2009","unstructured":"Candelario-Jalil E, Yang Y, Rosenberg GA. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience. 2009;158:983\u201394.","journal-title":"Neuroscience"},{"key":"1954_CR82","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1126\/science.1073634","volume":"297","author":"Z Gu","year":"2002","unstructured":"Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA. S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science. 2002;297:1186\u201390.","journal-title":"Science"},{"key":"1954_CR83","doi-asserted-by":"crossref","unstructured":"Perino A, Beretta M, Kilic A, Ghigo A, Carnevale D, Repetto IE, Braccini L, Longo D, Liebig-Gonglach M, Zaglia T, et al: Combined inhibition of PI3Kbeta and PI3Kgamma reduces fat mass by enhancing alpha-MSH-dependent sympathetic drive. Sci Signal 2014, 7:ra110.","DOI":"10.1126\/scisignal.2005485"},{"key":"1954_CR84","first-page":"123","volume":"9","author":"NR Saunders","year":"2015","unstructured":"Saunders NR, Dziegielewska KM, Mollgard K, Habgood MD, Wakefield MJ, Lindsay H, Stratzielle N, Ghersi-Egea JF, Liddelow SA. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study. Front Neurosci. 2015;9:123.","journal-title":"Front Neurosci"},{"key":"1954_CR85","doi-asserted-by":"publisher","first-page":"7628037","DOI":"10.1155\/2018\/7628037","volume":"2018","author":"L Yao","year":"2018","unstructured":"Yao L, Xue X, Yu P, Ni Y, Chen F. Evans blue dye: a revisit of its applications in biomedicine. Contrast Media Mol Imaging. 2018;2018:7628037.","journal-title":"Contrast Media Mol Imaging"},{"key":"1954_CR86","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1097\/00004647-200207000-00011","volume":"22","author":"AB Singhal","year":"2002","unstructured":"Singhal AB, Wang X, Sumii T, Mori T, Lo EH. Effects of normobaric hyperoxia in a rat model of focal cerebral ischemia-reperfusion. J Cereb Blood Flow Metab. 2002;22:861\u20138.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1954_CR87","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/BF00691332","volume":"54","author":"M Wolman","year":"1981","unstructured":"Wolman M, Klatzo I, Chui E, Wilmes F, Nishimoto K, Fujiwara K, Spatz M. Evaluation of the dye-protein tracers in pathophysiology of the blood-brain barrier. Acta Neuropathol. 1981;54:55\u201361.","journal-title":"Acta Neuropathol"},{"key":"1954_CR88","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1152\/ajplegacy.1947.151.1.26","volume":"151","author":"VH Le","year":"1947","unstructured":"Le VH, Fishman WH. Combination of Evans blue with plasma protein; its significance in capillary permeability studies, blood dye disappearance curves, and its use as a protein tag. Am J Physiol. 1947;151:26\u201333.","journal-title":"Am J Physiol"},{"key":"1954_CR89","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1007\/BF00343123","volume":"57","author":"M Emmett","year":"1985","unstructured":"Emmett M, Cerniglia CE, Crowle AJ. Differential serum protein binding of benzidine- and benzidine-congener based dyes and their derivatives. Arch Toxicol. 1985;57:130\u20135.","journal-title":"Arch Toxicol"},{"key":"1954_CR90","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1152\/ajplegacy.1950.161.3.473","volume":"161","author":"TH Allen","year":"1950","unstructured":"Allen TH, Orahovats PD. Combination of toluidine dye isomers with plasma albumin. Am J Physiol. 1950;161:473\u201382.","journal-title":"Am J Physiol"},{"key":"1954_CR91","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068595","volume":"8","author":"LF Yen","year":"2013","unstructured":"Yen LF, Wei VC, Kuo EY, Lai TW. Distinct patterns of cerebral extravasation by Evans blue and sodium fluorescein in rats. PLoS One. 2013;8:e68595.","journal-title":"PLoS One"},{"key":"1954_CR92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mcn.2016.11.002","volume":"78","author":"N Schneble","year":"2017","unstructured":"Schneble N, Schmidt C, Bauer R, Muller JP, Monajembashi S, Wetzker R. Phosphoinositide 3-kinase gamma ties chemoattractant- and adrenergic control of microglial motility. Mol Cell Neurosci. 2017;78:1\u20138.","journal-title":"Mol Cell Neurosci"},{"key":"1954_CR93","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1093\/brain\/awn109","volume":"132","author":"H Neumann","year":"2009","unstructured":"Neumann H, Kotter MR, Franklin RJ. Debris clearance by microglia: an essential link between degeneration and regeneration. Brain. 2009;132:288\u201395.","journal-title":"Brain"},{"key":"1954_CR94","doi-asserted-by":"publisher","first-page":"5468","DOI":"10.1007\/s12035-015-9472-z","volume":"53","author":"C Schmidt","year":"2016","unstructured":"Schmidt C, Frahm C, Schneble N, Muller JP, Brodhun M, Franco I, Witte OW, Hirsch E, Wetzker R, Bauer R. Phosphoinositide 3-kinase gamma restrains neurotoxic effects of microglia after focal brain ischemia. Mol Neurobiol. 2016;53:5468\u201379.","journal-title":"Mol Neurobiol"},{"key":"1954_CR95","doi-asserted-by":"publisher","first-page":"E1738","DOI":"10.1073\/pnas.1525528113","volume":"113","author":"ML Bennett","year":"2016","unstructured":"Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, Mulinyawe SB, Bohlen CJ, Adil A, Tucker A, et al. New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A. 2016;113:E1738\u201346.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1954_CR96","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.neuron.2017.04.043","volume":"94","author":"CJ Bohlen","year":"2017","unstructured":"Bohlen CJ, Bennett FC, Tucker AF, Collins HY, Mulinyawe SB, Barres BA. Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures. Neuron. 2017;94:759\u201373 e758.","journal-title":"Neuron"},{"key":"1954_CR97","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/1742-2094-9-115","volume":"9","author":"B Stansley","year":"2012","unstructured":"Stansley B, Post J, Hensley K. A comparative review of cell culture systems for the study of microglial biology in Alzheimer\u2019s disease. J Neuroinflammation. 2012;9:115.","journal-title":"J Neuroinflammation"},{"key":"1954_CR98","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1146\/annurev.immunol.021908.132528","volume":"27","author":"RM Ransohoff","year":"2009","unstructured":"Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009;27:119\u201345.","journal-title":"Annu Rev Immunol"},{"key":"1954_CR99","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/978-1-61779-170-3_4","volume":"758","author":"A Witting","year":"2011","unstructured":"Witting A, Moller T. Microglia cell culture: a primer for the novice. Methods Mol Biol. 2011;758:49\u201366.","journal-title":"Methods Mol Biol"},{"key":"1954_CR100","volume-title":"The principles of humane experimental technique. In","author":"WMS Russell","year":"1959","unstructured":"Russell WMS, Burch RL. The principles of humane experimental technique. In. London, UK: Methuen; 1959."},{"key":"1954_CR101","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/laban.1220","volume":"46","author":"H Wurbel","year":"2017","unstructured":"Wurbel H. More than 3Rs: the importance of scientific validity for harm-benefit analysis of animal research. Lab Anim (NY). 2017;46:164\u20136.","journal-title":"Lab Anim (NY)"},{"key":"1954_CR102","unstructured":"Roque PJ, Costa LG: Co-culture of neurons and microglia. Curr Protoc Toxicol 2017, 74:11 24 11-11 24 17."},{"key":"1954_CR103","doi-asserted-by":"crossref","unstructured":"Ni M, Aschner M: Neonatal rat primary microglia: isolation, culturing, and selected applications. Curr Protoc Toxicol 2010, Chapter 12:Unit 12 17.","DOI":"10.1002\/0471140856.tx1217s43"},{"key":"1954_CR104","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.jneumeth.2007.04.018","volume":"164","author":"AM Floden","year":"2007","unstructured":"Floden AM, Combs CK. Microglia repetitively isolated from in vitro mixed glial cultures retain their initial phenotype. J Neurosci Methods. 2007;164:218\u201324.","journal-title":"J Neurosci Methods"},{"key":"1954_CR105","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ddmod.2008.07.006","volume":"5","author":"MJ Carson","year":"2008","unstructured":"Carson MJ, Crane J, Xie AX. Modeling CNS microglia: the quest to identify predictive models. Drug Discov Today Dis Models. 2008;5:19\u201325.","journal-title":"Drug Discov Today Dis Models"},{"key":"1954_CR106","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.reprotox.2014.04.002","volume":"48","author":"AA Baburamani","year":"2014","unstructured":"Baburamani AA, Supramaniam VG, Hagberg H, Mallard C. Microglia toxicity in preterm brain injury. Reprod Toxicol. 2014;48:106\u201312.","journal-title":"Reprod Toxicol"},{"key":"1954_CR107","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s12974-015-0299-3","volume":"12","author":"FL Cardoso","year":"2015","unstructured":"Cardoso FL, Herz J, Fernandes A, Rocha J, Sepodes B, Brito MA, McGavern DB, Brites D. Systemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects. J Neuroinflammation. 2015;12:82.","journal-title":"J Neuroinflammation"},{"key":"1954_CR108","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":"1954_CR109","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s12974-017-0877-7","volume":"14","author":"L Lin","year":"2017","unstructured":"Lin L, Desai R, Wang X, Lo EH, Xing C. Characteristics of primary rat microglia isolated from mixed cultures using two different methods. J Neuroinflammation. 2017;14:101.","journal-title":"J Neuroinflammation"},{"key":"1954_CR110","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12974-017-0844-3","volume":"14","author":"P Shrivastava","year":"2017","unstructured":"Shrivastava P, Cabrera MA, Chastain LG, Boyadjieva NI, Jabbar S, Franklin T, Sarkar DK. Mu-opioid receptor and delta-opioid receptor differentially regulate microglial inflammatory response to control proopiomelanocortin neuronal apoptosis in the hypothalamus: effects of neonatal alcohol. J Neuroinflammation. 2017;14:83.","journal-title":"J Neuroinflammation"},{"key":"1954_CR111","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12974-017-0859-9","volume":"14","author":"B Vuong","year":"2017","unstructured":"Vuong B, Odero G, Rozbacher S, Stevenson M, Kereliuk SM, Pereira TJ, Dolinsky VW, Kauppinen TM. Exposure to gestational diabetes mellitus induces neuroinflammation, derangement of hippocampal neurons, and cognitive changes in rat offspring. J Neuroinflammation. 2017;14:80.","journal-title":"J Neuroinflammation"},{"key":"1954_CR112","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/s12974-018-1201-x","volume":"15","author":"J Sun","year":"2018","unstructured":"Sun J, Pan X, Christiansen LI, Yuan XL, Skovgaard K, Chatterton DEW, Kaalund SS, Gao F, Sangild PT, Pankratova S. Necrotizing enterocolitis is associated with acute brain responses in preterm pigs. J Neuroinflammation. 2018;15:180.","journal-title":"J Neuroinflammation"},{"key":"1954_CR113","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12974-019-1457-9","volume":"16","author":"XF Mao","year":"2019","unstructured":"Mao XF, Wu HY, Tang XQ, Ali U, Liu H, Wang YX. Activation of GPR40 produces mechanical antiallodynia via the spinal glial interleukin-10\/beta-endorphin pathway. J Neuroinflammation. 2019;16:84.","journal-title":"J Neuroinflammation"},{"key":"1954_CR114","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.tins.2019.09.004","volume":"42","author":"A Sierra","year":"2019","unstructured":"Sierra A, Paolicelli RC, Kettenmann H. Cien Anos de microglia: milestones in a century of microglial research. Trends Neurosci. 2019;42:778\u201392.","journal-title":"Trends Neurosci"},{"key":"1954_CR115","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 Rio-Hortega J, Rafael Iglesias-Rozas J, Garrosa M, Kettenmann H. The \u201cBig-Bang\u201d for modern glial biology: translation and comments on Pio del Rio-Hortega 1919 series of papers on microglia. Glia. 2016;64:1801\u201340.","journal-title":"Glia"},{"key":"1954_CR116","unstructured":"R\u0131o-Hortega P: El \u201ctercer elemento de los centros nerviosos\u201d. II. Intervenci on de la microgl\u0131a en los procesos patologicos (celulas en bastoncito y cuerpos granuloadiposos. Bol Soc Esp Biol 1919, VIII:91\u2013103."},{"key":"1954_CR117","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/1742-2094-8-125","volume":"8","author":"M Karlstetter","year":"2011","unstructured":"Karlstetter M, Lippe E, Walczak Y, Moehle C, Aslanidis A, Mirza M, Langmann T. Curcumin is a potent modulator of microglial gene expression and migration. J Neuroinflammation. 2011;8:125.","journal-title":"J Neuroinflammation"},{"key":"1954_CR118","first-page":"39","volume":"9","author":"S Lin","year":"2012","unstructured":"Lin S, Liang Y, Zhang J, Bian C, Zhou H, Guo Q, Xiong Y, Li S, Su B. Microglial TIR-domain-containing adapter-inducing interferon-beta (TRIF) deficiency promotes retinal ganglion cell survival and axon regeneration via nuclear factor-kappaB. J Neuroinflammation. 2012;9:39.","journal-title":"J Neuroinflammation"},{"key":"1954_CR119","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12974-014-0226-z","volume":"12","author":"Y Yuan","year":"2015","unstructured":"Yuan Y, Rangarajan P, Kan EM, Wu Y, Wu C, Ling EA. Scutellarin regulates the Notch pathway and affects the migration and morphological transformation of activated microglia in experimentally induced cerebral ischemia in rats and in activated BV-2 microglia. J Neuroinflammation. 2015;12:11.","journal-title":"J Neuroinflammation"},{"key":"1954_CR120","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/1742-2094-9-149","volume":"9","author":"H Jeon","year":"2012","unstructured":"Jeon H, Kim JH, Kim JH, Lee WH, Lee MS, Suk K. Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity. J Neuroinflammation. 2012;9:149.","journal-title":"J Neuroinflammation"},{"key":"1954_CR121","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/1742-2094-9-227","volume":"9","author":"M Horiuchi","year":"2012","unstructured":"Horiuchi M, Wakayama K, Itoh A, Kawai K, Pleasure D, Ozato K, Itoh T. Interferon regulatory factor 8\/interferon consensus sequence binding protein is a critical transcription factor for the physiological phenotype of microglia. J Neuroinflammation. 2012;9:227.","journal-title":"J Neuroinflammation"},{"key":"1954_CR122","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.neuroscience.2012.12.036","volume":"233","author":"C Schmidt","year":"2013","unstructured":"Schmidt C, Schneble N, Muller JP, Bauer R, Perino A, Marone R, Rybalkin SD, Wymann MP, Hirsch E, Wetzker R. Phosphoinositide 3-kinase gamma mediates microglial phagocytosis via lipid kinase-independent control of cAMP. Neuroscience. 2013;233:44\u201353.","journal-title":"Neuroscience"},{"key":"1954_CR123","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.bbrc.2010.07.116","volume":"399","author":"R Jin","year":"2010","unstructured":"Jin R, Yu S, Song Z, Quillin JW, Deasis DP, Penninger JM, Nanda A, Granger DN, Li G. Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and contributes to ischemia-induced microglial activation in acute experimental stroke. Biochem Biophys Res Commun. 2010;399:458\u201364.","journal-title":"Biochem Biophys Res Commun"},{"key":"1954_CR124","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.neuroscience.2019.06.001","volume":"415","author":"S Shang","year":"2019","unstructured":"Shang S, Liu L, Wu X, Fan F, Hu E, Wang L, Ding Y, Zhang Y, Lu X. Inhibition of PI3Kgamma by AS605240 protects tMCAO mice by attenuating pro-inflammatory signaling and cytokine release in reactive astrocytes. Neuroscience. 2019;415:107\u201320.","journal-title":"Neuroscience"},{"key":"1954_CR125","doi-asserted-by":"publisher","first-page":"e12","DOI":"10.1093\/cvr\/cvx085","volume":"113","author":"N Smart","year":"2017","unstructured":"Smart N, Pries AR, Dirnagl U. Dr Smart talks to Prof Pries and Prof Dirnagl on animal experimentation in biomedical research. Cardiovasc Res. 2017;113:e12\u20135.","journal-title":"Cardiovasc Res"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01954-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-020-01954-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01954-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T22:41:58Z","timestamp":1633560118000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-01954-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,7]]},"references-count":125,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1954"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-01954-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-21417\/v1","asserted-by":"object"}]},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,7]]},"assertion":[{"value":"4 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study involves animal experiment and includes a statement on ethics approval.","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"}}],"article-number":"292"}}