{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:18:10Z","timestamp":1792736290056,"version":"4.5.0"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS104083"],"award-info":[{"award-number":["NS104083"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601051"],"award-info":[{"award-number":["81601051"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hypoxic-ischemic encephalopathy (HIE) is a life-threatening cerebrovascular disease. Neuroinflammation plays an important role in the pathogenesis of HIE, in which microglia are key cellular mediators in the regulation of neuroinflammatory processes. Colony-stimulating factor 1 (CSF1), a specific endogenous ligand of CSF1 receptor (CSF1R), is crucial in microglial growth, differentiation, and proliferation. Recent studies showed that the activation of CSF1R with CSF1 exerted anti-inflammatory effects in a variety of nervous system diseases. This study aimed to investigate the anti-inflammatory effects of recombinant human CSF1 (rh-CSF1) and the underlying mechanisms in a rat model of HIE.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A total of 202 10-day old Sprague Dawley rat pups were used. HI was induced by the right common carotid artery ligation with subsequent exposure of 2.5-h hypoxia. At 1\u2009h and 24\u2009h after HI induction, exogenous rh-CSF1 was administered intranasally. To explore the underlying mechanism, CSF1R inhibitor, BLZ945, and phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, were injected intraperitoneally at 1\u2009h before HI induction, respectively. Brain infarct area, brain water content, neurobehavioral tests, western blot, and immunofluorescence staining were performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The expressions of endogenous CSF1, CSF1R, PLCG2, protein kinase C epsilon type (PKC\u03b5), and cAMP response element-binding protein (CREB) were gradually increased after HIE. Rh-CSF1 significantly improved the neurological deficits at 48\u2009h and 4\u2009weeks after HI, which was accompanied by a reduction in the brain infarct area, brain edema, brain atrophy, and neuroinflammation. Moreover, activation of CSF1R by rh-CSF1 significantly increased the expressions of p-PLCG2, p-PKC\u03b5, and p-CREB, but inhibited the activation of neutrophil infiltration, and downregulated the expressions of IL-1\u03b2 and TNF-\u03b1. Inhibition of CSF1R and PLCG2 abolished these neuroprotective effects of rh-CSF1 after HI.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings demonstrated that the activation of CSF1R by rh-CSF1 attenuated neuroinflammation and improved neurological deficits after HI. The anti-inflammatory effects of rh-CSF1 partially acted through activating the CSF1R\/PLCG2\/PKC\u03b5<jats:bold>\/<\/jats:bold>CREB signaling pathway after HI. These results suggest that rh-CSF1 may serve as a potential therapeutic approach to ameliorate injury in HIE patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-020-01862-w","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T07:02:50Z","timestamp":1591772570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Rh-CSF1 attenuates neuroinflammation via the CSF1R\/PLCG2\/PKC\u03b5 pathway in a rat model of neonatal HIE"],"prefix":"10.1186","volume":"17","author":[{"given":"Xiao","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desislava Met","family":"Doycheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Lenahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shucai","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-4285","authenticated-orcid":false,"given":"John H.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,10]]},"reference":[{"issue":"10","key":"1862_CR1","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.3390\/ijms20102449","volume":"20","author":"CA McDonald","year":"2019","unstructured":"McDonald CA, Djuliannisaa Z, Petraki M, Paton MCB, Penny TR, Sutherland AE, et al. Intranasal delivery of mesenchymal stromal cells protects against neonatal hypoxic(-)ischemic brain injury. Int J Mol Sci. 2019;20(10):2449.","journal-title":"Int J Mol Sci"},{"issue":"5","key":"1862_CR2","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.3390\/s20051424","volume":"20","author":"H Abbasi","year":"2020","unstructured":"Abbasi H, Gunn AJ, Bennet L, Unsworth CP. Latent phase identification of high-frequency micro-scale gamma spike transients in the hypoxic ischemic EEG of preterm fetal sheep using spectral analysis and fuzzy classifiers. sensors (Basel). 2020;20(5):1424.","journal-title":"sensors (Basel)"},{"issue":"5","key":"1862_CR3","doi-asserted-by":"publisher","first-page":"894","DOI":"10.4103\/1673-5374.268927","volume":"15","author":"M Li","year":"2020","unstructured":"Li M, Cui MM, Kenechukwu NA, Gu YW, Chen YL, Zhong SJ, et al. Rosmarinic acid ameliorates hypoxia\/ischemia induced cognitive deficits and promotes remyelination. Neural Regen Res. 2020;15(5):894\u2013902.","journal-title":"Neural Regen Res"},{"issue":"4","key":"1862_CR4","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1001\/jamapediatrics.2014.3269","volume":"169","author":"M Douglas-Escobar","year":"2015","unstructured":"Douglas-Escobar M, Weiss MD. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr. 2015;169(4):397\u2013403.","journal-title":"JAMA Pediatr"},{"key":"1862_CR5","doi-asserted-by":"crossref","unstructured":"Finder M, Boylan GB, Twomey D, Ahearne C, Murray DM, Hallberg B. Two-year neurodevelopmental outcomes after mild hypoxic ischemic encephalopathy in the era of therapeutic hypothermia. JAMA Pediatr. 2019.","DOI":"10.1001\/jamapediatrics.2019.4011"},{"key":"1862_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.earlhumdev.2018.08.003","volume":"125","author":"TI Herrera","year":"2018","unstructured":"Herrera TI, Edwards L, Malcolm WF, Smith PB, Fisher KA, Pizoli C, et al. Outcomes of preterm infants treated with hypothermia for hypoxic-ischemic encephalopathy. Early Hum Dev. 2018;125:1\u20137.","journal-title":"Early Hum Dev"},{"key":"1862_CR7","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.3389\/fimmu.2019.02199","volume":"10","author":"C Easley-Neal","year":"2019","unstructured":"Easley-Neal C, Foreman O, Sharma N, Zarrin AA, Weimer RM. CSF1R ligands IL-34 and CSF1 are differentially required for microglia development and maintenance in white and gray matter brain regions. Front Immunol. 2019;10:2199.","journal-title":"Front Immunol"},{"key":"1862_CR8","doi-asserted-by":"publisher","first-page":"103586","DOI":"10.1016\/j.dci.2019.103586","volume":"105","author":"Z Wu","year":"2020","unstructured":"Wu Z, Harne R, Chintoan-Uta C, Hu TJ, Wallace R, MacCallum A, et al. Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system. Dev Comp Immunol. 2020;105:103586.","journal-title":"Dev Comp Immunol"},{"issue":"6","key":"1862_CR9","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.tins.2016.03.005","volume":"39","author":"V Chitu","year":"2016","unstructured":"Chitu V, Gokhan S, Nandi S, Mehler MF, Stanley ER. Emerging roles for CSF-1 receptor and its ligands in the nervous system. Trends Neurosci. 2016;39(6):378\u201393.","journal-title":"Trends Neurosci"},{"issue":"10","key":"1862_CR10","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1084\/jem.20191535","volume":"216","author":"K Kierdorf","year":"2019","unstructured":"Kierdorf K, Prinz M. Microglia: same same, but different. J Exp Med. 2019;216(10):2223\u20135.","journal-title":"J Exp Med"},{"key":"1862_CR11","doi-asserted-by":"crossref","unstructured":"Wylot B, Mieczkowski J, Niedziolka S, Kaminska B, Zawadzka M. Csf1 Deficiency dysregulates glial responses to demyelination and disturbs CNS white matter remyelination. Cells. 2019;9(1) 99.","DOI":"10.3390\/cells9010099"},{"key":"1862_CR12","doi-asserted-by":"crossref","unstructured":"Stanley ER, Chitu V. CSF-1 receptor signaling in myeloid cells. Cold Spring Harb Perspect Biol. 2014;6(6).","DOI":"10.1101\/cshperspect.a021857"},{"issue":"405","key":"1862_CR13","doi-asserted-by":"publisher","first-page":"rs13","DOI":"10.1126\/scisignal.aaa6711","volume":"8","author":"Q Xu","year":"2015","unstructured":"Xu Q, Malecka KL, Fink L, Jordan EJ, Duffy E, Kolander S, et al. Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases. Sci Signal. 2015;8(405):rs13.","journal-title":"Sci Signal"},{"issue":"2","key":"1862_CR14","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.neuron.2014.02.040","volume":"82","author":"MR Elmore","year":"2014","unstructured":"Elmore MR, 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(2):380\u201397.","journal-title":"Neuron."},{"issue":"1","key":"1862_CR15","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1084\/jem.20120412","volume":"210","author":"J Luo","year":"2013","unstructured":"Luo J, Elwood F, Britschgi M, Villeda S, Zhang H, Ding Z, et al. Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival. J Exp Med. 2013;210(1):157\u201372.","journal-title":"J Exp Med"},{"key":"1862_CR16","doi-asserted-by":"publisher","first-page":"117664","DOI":"10.1016\/j.lfs.2020.117664","volume":"252","author":"Z Chen","year":"2020","unstructured":"Chen Z, Hu Y, Lu R, Ge M, Zhang L. MicroRNA-374a-5p inhibits neuroinflammation in neonatal hypoxic-ischemic encephalopathy via regulating NLRP3 inflammasome targeted Smad6. Life Sci. 2020;252:117664.","journal-title":"Life Sci"},{"issue":"4","key":"1862_CR17","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.nurt.2010.07.005","volume":"7","author":"MA Yenari","year":"2010","unstructured":"Yenari MA, Kauppinen TM, Swanson RA. Microglial activation in stroke: therapeutic targets. Neurotherapeutics. 2010;7(4):378\u201391.","journal-title":"Neurotherapeutics."},{"key":"1862_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneuroim.2018.02.015","volume":"318","author":"F Chu","year":"2018","unstructured":"Chu F, Shi M, Zheng C, Shen D, Zhu J, Zheng X, et al. The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neuroimmunol. 2018;318:1\u20137.","journal-title":"J Neuroimmunol"},{"issue":"2","key":"1862_CR19","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1083\/jcb.201709069","volume":"217","author":"DV Hansen","year":"2018","unstructured":"Hansen DV, Hanson JE, Sheng M. Microglia in Alzheimer's disease. J Cell Biol. 2018;217(2):459\u201372.","journal-title":"J Cell Biol"},{"issue":"5","key":"1862_CR20","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/j.celrep.2018.06.113","volume":"24","author":"N Oosterhof","year":"2018","unstructured":"Oosterhof N, Kuil LE, van der Linde HC, Burm SM, Berdowski W, van Ijcken WFJ, et al. Colony-stimulating factor 1 receptor (CSF1R) regulates microglia density and distribution, but not microglia differentiation in vivo. Cell Rep. 2018;24(5):1203\u201317 e6.","journal-title":"Cell Rep"},{"key":"1862_CR21","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.3389\/fimmu.2019.02019","volume":"10","author":"W Lin","year":"2019","unstructured":"Lin W, Xu D, Austin CD, Caplazi P, Senger K, Sun Y, et al. Function of CSF1 and IL34 in macrophage homeostasis, inflammation, and cancer. Front Immunol. 2019;10:2019.","journal-title":"Front Immunol"},{"issue":"1","key":"1862_CR22","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.1038\/s41467-019-11674-z","volume":"10","author":"E Spangenberg","year":"2019","unstructured":"Spangenberg E, Severson PL, Hohsfield LA, Crapser J, Zhang J, Burton EA, et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model. Nat Commun. 2019;10(1):3758.","journal-title":"Nat Commun"},{"issue":"6","key":"1862_CR23","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1111\/bpa.12731","volume":"29","author":"DL Irons","year":"2019","unstructured":"Irons DL, Meinhardt T, Allers C, Kuroda MJ, Kim WK. Overexpression and activation of colony-stimulating factor 1 receptor in the SIV\/macaque model of HIV infection and neuroHIV. Brain Pathol. 2019;29(6):826\u201336.","journal-title":"Brain Pathol"},{"key":"1862_CR24","doi-asserted-by":"publisher","first-page":"523","DOI":"10.3389\/fncel.2018.00523","volume":"12","author":"A Wlodarczyk","year":"2018","unstructured":"Wlodarczyk A, Benmamar-Badel A, Cedile O, Jensen KN, Kramer I, Elsborg NB, et al. CSF1R stimulation promotes increased neuroprotection by CD11c + microglia in EAE. Front Cell Neurosci. 2018;12:523.","journal-title":"Front Cell Neurosci"},{"issue":"2","key":"1862_CR25","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s00401-018-1954-4","volume":"137","author":"A Otxoa-de-Amezaga","year":"2019","unstructured":"Otxoa-de-Amezaga A, Miro-Mur F, Pedragosa J, Gallizioli M, Justicia C, Gaja-Capdevila N, et al. Microglial cell loss after ischemic stroke favors brain neutrophil accumulation. Acta Neuropathol. 2019;137(2):321\u201341.","journal-title":"Acta Neuropathol"},{"issue":"6","key":"1862_CR26","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1177\/0271678X17694185","volume":"37","author":"WN Jin","year":"2017","unstructured":"Jin WN, Shi SX, Li Z, Li M, Wood K, Gonzales RJ, et al. Depletion of microglia exacerbates postischemic inflammation and brain injury. J Cereb Blood Flow Metab. 2017;37(6):2224\u201336.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"1862_CR27","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/jcb.24653","volume":"115","author":"CM Barbosa","year":"2014","unstructured":"Barbosa CM, Bincoletto C, Barros CC, Ferreira AT, Paredes-Gamero EJ. PLCgamma2 and PKC are important to myeloid lineage commitment triggered by M-SCF and G-CSF. J Cell Biochem. 2014;115(1):42\u201351.","journal-title":"J Cell Biochem"},{"issue":"7","key":"1862_CR28","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1080\/15548627.2015.1034406","volume":"11","author":"S Obba","year":"2015","unstructured":"Obba S, Hizir Z, Boyer L, Selimoglu-Buet D, Pfeifer A, Michel G, et al. The PRKAA1\/AMPKalpha1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML. Autophagy. 2015;11(7):1114\u201329.","journal-title":"Autophagy."},{"issue":"1","key":"1862_CR29","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13195-019-0469-0","volume":"11","author":"L Magno","year":"2019","unstructured":"Magno L, Lessard CB, Martins M, Lang V, Cruz P, Asi Y, et al. Alzheimer's disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph. Alzheimers Res Ther. 2019;11(1):16.","journal-title":"Alzheimers Res Ther"},{"issue":"2","key":"1862_CR30","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1091\/mbc.e04-12-1100","volume":"17","author":"KL Cheeseman","year":"2006","unstructured":"Cheeseman KL, Ueyama T, Michaud TM, Kashiwagi K, Wang D, Flax LA, et al. Targeting of protein kinase C-epsilon during Fcgamma receptor-dependent phagocytosis requires the epsilonC1B domain and phospholipase C-gamma1. Mol Biol Cell. 2006;17(2):799\u2013813.","journal-title":"Mol Biol Cell"},{"issue":"4","key":"1862_CR31","first-page":"315","volume":"161","author":"Y Nakamura","year":"2017","unstructured":"Nakamura Y, Fukami K. Regulation and physiological functions of mammalian phospholipase C. J Biochem. 2017;161(4):315\u201321.","journal-title":"J Biochem"},{"issue":"1","key":"1862_CR32","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s12868-018-0479-z","volume":"19","author":"V Kumar","year":"2018","unstructured":"Kumar V, Weng YC, Wu YC, Huang YT, Chou WH. PKCepsilon phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration. BMC Neurosci. 2018;19(1):76.","journal-title":"BMC Neurosci"},{"key":"1862_CR33","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, et al. Activation of TGR5 with INT-777 attenuates oxidative stress and neuronal apoptosis via cAMP\/PKCepsilon\/ALDH2 pathway after subarachnoid hemorrhage in rats. Free Radic Biol Med. 2019;143:441\u201353.","journal-title":"Free Radic Biol Med"},{"issue":"17","key":"1862_CR34","doi-asserted-by":"publisher","first-page":"2813","DOI":"10.1002\/1873-3468.12313","volume":"590","author":"S Gessi","year":"2016","unstructured":"Gessi S, Borea PA, Bencivenni S, Fazzi D, Varani K, Merighi S. The activation of mu-opioid receptor potentiates LPS-induced NF-kB promoting an inflammatory phenotype in microglia. FEBS Lett. 2016;590(17):2813\u201326.","journal-title":"FEBS Lett"},{"issue":"15","key":"1862_CR35","doi-asserted-by":"publisher","first-page":"3776","DOI":"10.3390\/ijms20153776","volume":"20","author":"A Derouiche","year":"2019","unstructured":"Derouiche A, Geiger KD. Perspectives for Ezrin and radixin in astrocytes: kinases, functions and pathology. Int J Mol Sci. 2019;20(15):3776.","journal-title":"Int J Mol Sci"},{"issue":"3","key":"1862_CR36","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1093\/cvr\/cvv131","volume":"106","author":"H Mylroie","year":"2015","unstructured":"Mylroie H, Dumont O, Bauer A, Thornton CC, Mackey J, Calay D, et al. PKCepsilon-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis. Cardiovasc Res. 2015;106(3):509\u201319.","journal-title":"Cardiovasc Res"},{"key":"1862_CR37","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.3389\/fphar.2019.01245","volume":"10","author":"X Guan","year":"2019","unstructured":"Guan X, Wang Y, Kai G, Zhao S, Huang T, Li Y, et al. Cerebrolysin ameliorates focal cerebral ischemia injury through neuroinflammatory inhibition via CREB\/PGC-1alpha pathway. Front Pharmacol. 2019;10:1245.","journal-title":"Front Pharmacol"},{"issue":"9","key":"1862_CR38","doi-asserted-by":"publisher","first-page":"6341","DOI":"10.1007\/s12035-019-1518-1","volume":"56","author":"J Jaworska","year":"2019","unstructured":"Jaworska J, Zalewska T, Sypecka J, Ziemka-Nalecz M. Effect of the HDAC inhibitor, sodium butyrate, on neurogenesis in a rat model of neonatal hypoxia-ischemia: potential mechanism of action. Mol Neurobiol. 2019;56(9):6341\u201370.","journal-title":"Mol Neurobiol"},{"issue":"2","key":"1862_CR39","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/ana.410090206","volume":"9","author":"JE Rice 3rd","year":"1981","unstructured":"Rice JE 3rd, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 1981;9(2):131\u201341.","journal-title":"Ann Neurol"},{"issue":"4","key":"1862_CR40","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1007\/s12975-015-0397-7","volume":"6","author":"H Dock","year":"2015","unstructured":"Dock H, Theodorsson A, Theodorsson E. DNA methylation inhibitor Zebularine confers stroke protection in ischemic rats. Transl Stroke Res. 2015;6(4):296\u2013300.","journal-title":"Transl Stroke Res"},{"issue":"1","key":"1862_CR41","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s12975-017-0559-x","volume":"9","author":"Z Wang","year":"2018","unstructured":"Wang Z, Zhou F, Dou Y, Tian X, Liu C, Li H, et al. Melatonin alleviates intracerebral hemorrhage-induced secondary brain injury in rats via suppressing apoptosis, inflammation, oxidative stress, DNA damage, and mitochondria injury. Transl Stroke Res. 2018;9(1):74\u201391.","journal-title":"Transl Stroke Res"},{"issue":"1","key":"1862_CR42","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s12975-018-0624-0","volume":"10","author":"M Tanaka","year":"2019","unstructured":"Tanaka M, Ogaeri T, Samsonov M, Sokabe M. The 5alpha-reductase inhibitor finasteride exerts neuroprotection against ischemic brain injury in aged male rats. Transl Stroke Res. 2019;10(1):67\u201377.","journal-title":"Transl Stroke Res"},{"issue":"4","key":"1862_CR43","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1007\/s12975-018-0644-9","volume":"10","author":"EV Griemert","year":"2019","unstructured":"Griemert EV, Recarte Pelz K, Engelhard K, Schafer MK, Thal SC. PAI-1 but not PAI-2 gene deficiency attenuates ischemic brain injury after experimental stroke. Transl Stroke Res. 2019;10(4):372\u201380.","journal-title":"Transl Stroke Res"},{"issue":"1","key":"1862_CR44","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/s12975-018-0669-0","volume":"10","author":"H Liu","year":"2019","unstructured":"Liu H, Hua Y, Keep RF, Xi G. Brain ceruloplasmin expression after experimental intracerebral hemorrhage and protection against iron-induced brain injury. Transl Stroke Res. 2019;10(1):112\u20139.","journal-title":"Transl Stroke Res"},{"key":"1862_CR45","doi-asserted-by":"crossref","unstructured":"Zhang Y, Zhang X, Wei Q, Leng S, Li C, Han B, et al. Activation of sigma-1 receptor enhanced pericyte survival via the interplay between apoptosis and autophagy: implications for blood-brain barrier integrity in stroke. Transl Stroke Res. 2019.","DOI":"10.1007\/s12975-020-00849-2"},{"key":"1862_CR46","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3389\/fnagi.2017.00244","volume":"9","author":"DG Walker","year":"2017","unstructured":"Walker DG, Tang TM, Lue LF. Studies on colony stimulating factor receptor-1 and ligands colony stimulating factor-1 and interleukin-34 in Alzheimer's disease brains and human microglia. Front Aging Neurosci. 2017;9:244.","journal-title":"Front Aging Neurosci"},{"issue":"1","key":"1862_CR47","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1186\/s12974-016-0757-6","volume":"13","author":"N Borjini","year":"2016","unstructured":"Borjini N, Fernandez M, Giardino L, Calza L. Cytokine and chemokine alterations in tissue, CSF, and plasma in early presymptomatic phase of experimental allergic encephalomyelitis (EAE), in a rat model of multiple sclerosis. J Neuroinflammation. 2016;13(1):291.","journal-title":"J Neuroinflammation"},{"issue":"3","key":"1862_CR48","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/jnen\/nlx115","volume":"77","author":"AC Knight","year":"2018","unstructured":"Knight AC, Brill SA, Queen SE, Tarwater PM, Mankowski JL. Increased microglial CSF1R expression in the SIV\/macaque model of HIV CNS disease. J Neuropathol Exp Neurol. 2018;77(3):199\u2013206.","journal-title":"J Neuropathol Exp Neurol"},{"key":"1862_CR49","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.expneurol.2018.05.021","volume":"307","author":"JC Nissen","year":"2018","unstructured":"Nissen JC, Thompson KK, West BL, Tsirka SE. Csf1R inhibition attenuates experimental autoimmune encephalomyelitis and promotes recovery. Exp Neurol. 2018;307:24\u201336.","journal-title":"Exp Neurol"},{"issue":"4","key":"1862_CR50","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.1002\/jcb.26477","volume":"119","author":"X Liu","year":"2018","unstructured":"Liu X, Ma Y, Wei X, Fan T. Neuroprotective effect of licochalcone a against oxygen-glucose deprivation\/reperfusion in rat primary cortical neurons by attenuating oxidative stress injury and inflammatory response via the SIRT1\/Nrf2 pathway. J Cell Biochem. 2018;119(4):3210\u20139.","journal-title":"J Cell Biochem"},{"issue":"1","key":"1862_CR51","doi-asserted-by":"publisher","first-page":"009","DOI":"10.19104\/jnn.2015.91","volume":"2","author":"MB Chauhan","year":"2015","unstructured":"Chauhan MB, Chauhan NB. Brain uptake of Neurotherapeutics after intranasal versus intraperitoneal delivery in mice. J Neurol Neurosurg. 2015;2(1):009.","journal-title":"J Neurol Neurosurg"},{"issue":"1","key":"1862_CR52","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3340\/jkns.2015.58.1.22","volume":"58","author":"JH Byeon","year":"2015","unstructured":"Byeon JH, Kim GH, Kim JY, Sun W, Kim H, Eun BL. Cognitive dysfunction and hippocampal damage induced by hypoxic-ischemic brain injury and prolonged febrile convulsions in immature rats. J Korean Neurosurg Soc. 2015;58(1):22\u20139.","journal-title":"J Korean Neurosurg Soc"},{"key":"1862_CR53","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s11556-019-0217-2","volume":"16","author":"F Herold","year":"2019","unstructured":"Herold F, Torpel A, Schega L, Muller NG. Functional and\/or structural brain changes in response to resistance exercises and resistance training lead to cognitive improvements - a systematic review. Eur Rev Aging Phys Act. 2019;16:10.","journal-title":"Eur Rev Aging Phys Act"},{"issue":"10","key":"1862_CR54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026317","volume":"6","author":"B Erblich","year":"2011","unstructured":"Erblich B, Zhu L, Etgen AM, Dobrenis K, Pollard JW. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS One. 2011;6(10):e26317.","journal-title":"PLoS One"},{"issue":"3","key":"1862_CR55","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1002\/(SICI)1096-9861(19980808)395:3<342::AID-CNE6>3.0.CO;2-2","volume":"395","author":"G Raivich","year":"1998","unstructured":"Raivich G, Haas S, Werner A, Klein MA, Kloss C, Kreutzberg GW. Regulation of MCSF receptors on microglia in the normal and injured mouse central nervous system: a quantitative immunofluorescence study using confocal laser microscopy. J Comp Neurol. 1998;395(3):342\u201358.","journal-title":"J Comp Neurol"},{"issue":"12","key":"1862_CR56","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1002\/glia.22717","volume":"62","author":"I De","year":"2014","unstructured":"De I, Nikodemova M, Steffen MD, Sokn E, Maklakova VI, Watters JJ, et al. CSF1 overexpression has pleiotropic effects on microglia in vivo. Glia. 2014;62(12):1955\u201367.","journal-title":"Glia."},{"issue":"10","key":"1862_CR57","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.3390\/jcm8101529","volume":"8","author":"KH Chang","year":"2019","unstructured":"Chang KH, Wu YR, Chen YC, Wu HC, Chen CM. Association between CSF1 and CSF1R polymorphisms and Parkinson's disease in Taiwan. J Clin Med. 2019;8(10):1529.","journal-title":"J Clin Med"},{"issue":"5","key":"1862_CR58","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1073\/pnas.1812155116","volume":"116","author":"AG Horti","year":"2019","unstructured":"Horti AG, Naik R, Foss CA, Minn I, Misheneva V, Du Y, et al. PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R). Proc Natl Acad Sci U S A. 2019;116(5):1686\u201391.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"1862_CR59","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1096\/fj.201900567RR","volume":"34","author":"ML Neal","year":"2020","unstructured":"Neal ML, Fleming SM, Budge KM, Boyle AM, Kim C, Alam G, et al. Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration. FASEB J. 2020;34(1):1679\u201394.","journal-title":"FASEB J"},{"issue":"8","key":"1862_CR60","doi-asserted-by":"publisher","first-page":"5245","DOI":"10.4049\/jimmunol.178.8.5245","volume":"178","author":"AJ Fleetwood","year":"2007","unstructured":"Fleetwood AJ, Lawrence T, Hamilton JA, Cook AD. Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation. J Immunol. 2007;178(8):5245\u201352.","journal-title":"J Immunol"},{"issue":"1","key":"1862_CR61","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/s12974-017-1011-6","volume":"14","author":"G Pepe","year":"2017","unstructured":"Pepe G, De Maglie M, Minoli L, Villa A, Maggi A, Vegeto E. Selective proliferative response of microglia to alternative polarization signals. J Neuroinflammation. 2017;14(1):236.","journal-title":"J Neuroinflammation"},{"issue":"8","key":"1862_CR62","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1007\/s10571-015-0209-3","volume":"35","author":"Y Miao","year":"2015","unstructured":"Miao Y, He T, Zhu Y, Li W, Wang B, Zhong Y. Activation of hippocampal CREB by rolipram partially recovers balance between TNF-alpha and IL-10 levels and improves cognitive deficits in diabetic rats. Cell Mol Neurobiol. 2015;35(8):1157\u201364.","journal-title":"Cell Mol Neurobiol"},{"issue":"2","key":"1862_CR63","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/S0306-4522(98)00352-2","volume":"89","author":"BR Hu","year":"1999","unstructured":"Hu BR, Fux CM, Martone ME, Zivin JA, Ellisman MH. Persistent phosphorylation of cyclic AMP responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain. Neuroscience. 1999;89(2):437\u201352.","journal-title":"Neuroscience."},{"issue":"9","key":"1862_CR64","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.3390\/ijms19092573","volume":"19","author":"PL Hung","year":"2018","unstructured":"Hung PL, Hsu MH, Yu HR, Wu KLH, Wang FS. Thyroxin protects white matter from hypoxic-ischemic insult in the immature Sprague(-)Dawley rat brain by regulating periventricular white matter and cortex BDNF and CREB pathways. Int J Mol Sci. 2018;19(9):2573.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1862_CR65","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s13024-018-0289-x","volume":"13","author":"OJ Conway","year":"2018","unstructured":"Conway OJ, Carrasquillo MM, Wang X, Bredenberg JM, Reddy JS, Strickland SL, et al. ABI3 and PLCG2 missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans. Mol Neurodegener. 2018;13(1):53.","journal-title":"Mol Neurodegener"},{"issue":"2","key":"1862_CR66","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s00401-019-02026-8","volume":"138","author":"SJ van der Lee","year":"2019","unstructured":"van der Lee SJ, Conway OJ, Jansen I, Carrasquillo MM, Kleineidam L, van den Akker E, et al. A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity. Acta Neuropathol. 2019;138(2):237\u201350.","journal-title":"Acta Neuropathol"},{"issue":"5","key":"1862_CR67","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/nrc.2017.17","volume":"17","author":"P Gotwals","year":"2017","unstructured":"Gotwals P, Cameron S, Cipolletta D, Cremasco V, Crystal A, Hewes B, et al. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 2017;17(5):286\u2013301.","journal-title":"Nat Rev Cancer"},{"key":"1862_CR68","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3389\/fnmol.2016.00111","volume":"9","author":"DF Gilbert","year":"2016","unstructured":"Gilbert DF, Stebbing MJ, Kuenzel K, Murphy RM, Zacharewicz E, Buttgereit A, et al. Store-operated ca(2+) entry (SOCE) and purinergic receptor-mediated ca(2+) homeostasis in murine bv2 microglia cells: early cellular responses to ATP-mediated microglia activation. Front Mol Neurosci. 2016;9:111.","journal-title":"Front Mol Neurosci"},{"issue":"3","key":"1862_CR69","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.celrep.2017.12.066","volume":"22","author":"BA Friedman","year":"2018","unstructured":"Friedman BA, Srinivasan K, Ayalon G, Meilandt WJ, Lin H, Huntley MA, et al. Diverse brain myeloid expression profiles reveal distinct microglial activation states and aspects of Alzheimer's disease not evident in mouse models. Cell Rep. 2018;22(3):832\u201347.","journal-title":"Cell Rep"},{"key":"1862_CR70","first-page":"5201759","volume":"2018","author":"L Zhu","year":"2018","unstructured":"Zhu L, Jones C, Zhang G. The role of phospholipase C signaling in macrophage-mediated inflammatory response. J Immunol Res. 2018;2018:5201759.","journal-title":"J Immunol Res"},{"issue":"9","key":"1862_CR71","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1016\/j.cellsig.2014.05.002","volume":"26","author":"AA Waza","year":"2014","unstructured":"Waza AA, Andrabi K, Hussain MU. Protein kinase C (PKC) mediated interaction between conexin43 (Cx43) and K(+)(ATP) channel subunit (Kir6.1) in cardiomyocyte mitochondria: implications in cytoprotection against hypoxia induced cell apoptosis. Cell Signal. 2014;26(9):1909\u201317.","journal-title":"Cell Signal"},{"issue":"11","key":"1862_CR72","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1007\/s11064-019-02876-4","volume":"44","author":"D Surendran","year":"2019","unstructured":"Surendran D. PKCgamma and PKCepsilon are differentially activated and modulate neurotoxic signaling pathways during oxygen glucose deprivation in rat cortical slices. Neurochem Res. 2019;44(11):2577\u201389.","journal-title":"Neurochem Res"},{"issue":"9","key":"1862_CR73","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/aps.2013.89","volume":"34","author":"F Liu","year":"2013","unstructured":"Liu F, McCullough LD. Inflammatory responses in hypoxic ischemic encephalopathy. Acta Pharmacol Sin. 2013;34(9):1121\u201330.","journal-title":"Acta Pharmacol Sin"},{"key":"1862_CR74","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.neuint.2018.12.014","volume":"127","author":"A Al Mamun","year":"2019","unstructured":"Al Mamun A, Yu H, Mirza MA, Romana S, McCullough LD, Liu F. Myeloid cell IRF4 signaling protects neonatal brains from hypoxic ischemic encephalopathy. Neurochem Int. 2019;127:148\u201357.","journal-title":"Neurochem Int"},{"issue":"2","key":"1862_CR75","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1111\/j.1365-2990.1994.tb01173.x","volume":"20","author":"MR Del Bigio","year":"1994","unstructured":"Del Bigio MR, Becker LE. Microglial aggregation in the dentate gyrus: a marker of mild hypoxic-ischaemic brain insult in human infants. Neuropathol Appl Neurobiol. 1994;20(2):144\u201351.","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"3","key":"1862_CR76","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3390\/brainsci10030159","volume":"10","author":"C Rawlinson","year":"2020","unstructured":"Rawlinson C, Jenkins S, Thei L, Dallas ML, Chen R. Post-ischaemic immunological response in the brain: targeting microglia in ischaemic stroke therapy. Brain Sci. 2020;10(3):159.","journal-title":"Brain Sci"},{"issue":"1","key":"1862_CR77","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12974-020-01792-7","volume":"17","author":"S Tsuji","year":"2020","unstructured":"Tsuji S, Di Martino E, Mukai T, Tsuji S, Murakami T, Harris RA, et al. Aggravated brain injury after neonatal hypoxic ischemia in microglia-depleted mice. J Neuroinflammation. 2020;17(1):111.","journal-title":"J Neuroinflammation"},{"key":"1862_CR78","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/bs.ctdb.2016.10.004","volume":"123","author":"V Chitu","year":"2017","unstructured":"Chitu V, Stanley ER. Regulation of embryonic and postnatal development by the CSF-1 receptor. Curr Top Dev Biol. 2017;123:229\u201375.","journal-title":"Curr Top Dev Biol"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01862-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-020-01862-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01862-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T23:06:46Z","timestamp":1623280006000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-01862-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,10]]},"references-count":78,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1862"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-01862-w","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,10]]},"assertion":[{"value":"24 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"182"}}