{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T21:09:33Z","timestamp":1766869773424,"version":"3.37.3"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018-02682"],"award-info":[{"award-number":["2018-02682"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","award":["FO2017-0102"],"award-info":[{"award-number":["FO2017-0102"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ALF-agreement","award":["ALFGBG-813291"],"award-info":[{"award-number":["ALFGBG-813291"]}]},{"DOI":"10.13039\/501100005760","name":"University of Gothenburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005760","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteopontin (OPN) is a matricellular protein that mediates various physiological functions and is implicated in neuroinflammation, myelination, and perinatal brain injury. However, its expression in association with brain injury in preterm infants is unexplored. Here we examined the expression of OPN in postmortem brains of preterm infants and explored how this expression is affected in brain injury. We analyzed brain sections from cases with white matter injury (WMI) and cases with germinal matrix hemorrhage (GMH) and compared them to control cases having no brain injury. WMI cases displayed moderate to severe tissue injury in the periventricular and deep white matter that was accompanied by an increase of microglia with amoeboid morphology. Apart from visible hemorrhage in the germinal matrix, GMH cases displayed diffuse white matter injury in the periventricular and deep white matter. In non-injured preterm brains, OPN was expressed at low levels in microglia, astrocytes, and oligodendrocytes. OPN expression was significantly increased in regions with white matter injury in both WMI cases and GMH cases. The main cellular source of OPN in white matter injury areas was amoeboid microglia, although a significant increase was also observed in astrocytes in WMI cases. OPN was not expressed in the germinal matrix of any case, regardless of whether there was hemorrhage. In conclusion, preterm brain injury induces elevated OPN expression in microglia and astrocytes, and this increase is found in sites closely related to injury in the white matter regions but not with the hemorrhage site in the germinal matrix. Thus, it appears that OPN takes part in the inflammatory process in white matter injury in preterm infants, and these findings facilitate our understanding of OPN\u2019s role under both physiological and pathological conditions in the human brain that may lead to greater elucidation of disease mechanisms and potentially better treatment strategies.<\/jats:p>","DOI":"10.1186\/s40478-021-01267-7","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T20:24:15Z","timestamp":1634329455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["White matter injury but not germinal matrix hemorrhage induces elevated osteopontin expression in human preterm brains"],"prefix":"10.1186","volume":"9","author":[{"given":"Gisela","family":"Nilsson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana A.","family":"Baburamani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary A.","family":"Rutherford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changlian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"Mallard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Hagberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Vontell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-8160","authenticated-orcid":false,"given":"Xiaoyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"1267_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1186\/s12974-014-0197-0","volume":"11","author":"AM Albertsson","year":"2014","unstructured":"Albertsson AM, Zhang X, Leavenworth J, Bi D, Nair S, Qiao L, Hagberg H, Mallard C, Cantor H, Wang X (2014) The effect of osteopontin and osteopontin-derived peptides on preterm brain injury. J Neuroinflammation 11:197. https:\/\/doi.org\/10.1186\/s12974-014-0197-0","journal-title":"J Neuroinflammation"},{"key":"1267_CR2","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1001\/archpedi.1987.04460060035027","volume":"141","author":"DL Armstrong","year":"1987","unstructured":"Armstrong DL, Sauls CD, Goddard-Finegold J (1987) Neuropathologic findings in short-term survivors of intraventricular hemorrhage. Am J Dis Child 141:617\u2013621. https:\/\/doi.org\/10.1001\/archpedi.1987.04460060035027","journal-title":"Am J Dis Child"},{"key":"1267_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218343","author":"I Atienza-Navarro","year":"2020","unstructured":"Atienza-Navarro I, Alves-Martinez P, Lubian-Lopez S, Garcia-Alloza M (2020) Germinal matrix-intraventricular hemorrhage of the preterm newborn and preclinical models: inflammatory considerations. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms21218343","journal-title":"Int J Mol Sci"},{"key":"1267_CR4","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 (2014) Microglia toxicity in preterm brain injury. Reprod Toxicol 48:106\u2013112. https:\/\/doi.org\/10.1016\/j.reprotox.2014.04.002","journal-title":"Reprod Toxicol"},{"key":"1267_CR5","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s00401-017-1718-6","volume":"134","author":"SA Back","year":"2017","unstructured":"Back SA (2017) White matter injury in the preterm infant: pathology and mechanisms. Acta Neuropathol 134:331\u2013349. https:\/\/doi.org\/10.1007\/s00401-017-1718-6","journal-title":"Acta Neuropathol"},{"key":"1267_CR6","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/sj.jcbfm.9600344","volume":"27","author":"SA Back","year":"2007","unstructured":"Back SA, Craig A, Kayton RJ, Luo NL, Meshul CK, Allcock N, Fern R (2007) Hypoxia-ischemia preferentially triggers glutamate depletion from oligodendroglia and axons in perinatal cerebral white matter. J Cerebral Blood Flow metabol Offic J Int Soc Cerebral Blood Flow Metabol 27:334\u2013347. https:\/\/doi.org\/10.1038\/sj.jcbfm.9600344","journal-title":"J Cerebral Blood Flow metabol Offic J Int Soc Cerebral Blood Flow Metabol"},{"key":"1267_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1203\/PDR.0b013e3181c1b176","volume":"67","author":"P Ballabh","year":"2010","unstructured":"Ballabh P (2010) Intraventricular Hemorrhage in premature infants: mechanism of disease. Pediatr Res 67:1\u20138","journal-title":"Pediatr Res"},{"key":"1267_CR8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.clp.2013.09.007","volume":"41","author":"P Ballabh","year":"2014","unstructured":"Ballabh P (2014) Pathogenesis and prevention of intraventricular hemorrhage. Clin Perinatol 41:47\u201367. https:\/\/doi.org\/10.1016\/j.clp.2013.09.007","journal-title":"Clin Perinatol"},{"key":"1267_CR9","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41582-020-00447-8","volume":"17","author":"P Ballabh","year":"2021","unstructured":"Ballabh P, de Vries LS (2021) White matter injury in infants with intraventricular haemorrhage: mechanisms and therapies. Nat Rev Neurol 17:199\u2013214. https:\/\/doi.org\/10.1038\/s41582-020-00447-8","journal-title":"Nat Rev Neurol"},{"key":"1267_CR10","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/cne.20991","volume":"497","author":"SS Billiards","year":"2006","unstructured":"Billiards SS, Haynes RL, Folkerth RD, Trachtenberg FL, Liu LG, Volpe JJ, Kinney HC (2006) Development of microglia in the cerebral white matter of the human fetus and infant. J Comp Neurol 497:199\u2013208. https:\/\/doi.org\/10.1002\/cne.20991","journal-title":"J Comp Neurol"},{"key":"1267_CR11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/nan.12011","volume":"39","author":"D Boche","year":"2013","unstructured":"Boche D, Perry VH, Nicoll JAR (2013) Review: Activation patterns of microglia and their identification in the human brain. Neuropath Appl Neuro 39:3\u201318. https:\/\/doi.org\/10.1111\/nan.12011","journal-title":"Neuropath Appl Neuro"},{"key":"1267_CR12","doi-asserted-by":"publisher","first-page":"249","DOI":"10.2174\/187152810793358778","volume":"9","author":"M Braitch","year":"2010","unstructured":"Braitch M, Constantinescu CS (2010) The role of osteopontin in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). Inflamm Allergy Drug Targets 9:249\u2013256. https:\/\/doi.org\/10.2174\/187152810793358778","journal-title":"Inflamm Allergy Drug Targets"},{"key":"1267_CR13","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/nri2460","volume":"9","author":"H Cantor","year":"2009","unstructured":"Cantor H, Shinohara ML (2009) Regulation of T-helper-cell lineage development by osteopontin: the inside story. Nat Rev Immunol 9:137\u2013141. https:\/\/doi.org\/10.1038\/nri2460","journal-title":"Nat Rev Immunol"},{"key":"1267_CR14","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.4103\/1673-5374.300328","volume":"16","author":"G Cappellano","year":"2021","unstructured":"Cappellano G, Vecchio D, Magistrelli L, Clemente N, Raineri D, Barbero Mazzucca C, Virgilio E, Dianzani U, Chiocchetti A, Comi C (2021) The Yin-Yang of osteopontin in nervous system diseases: damage versus repair. Neural Regen Res 16:1131\u20131137. https:\/\/doi.org\/10.4103\/1673-5374.300328","journal-title":"Neural Regen Res"},{"key":"1267_CR15","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1126\/science.1062960","volume":"294","author":"D Chabas","year":"2001","unstructured":"Chabas D, Baranzini SE, Mitchell D, Bernard CC, Rittling SR, Denhardt DT, Sobel RA, Lock C, Karpuj M, Pedotti R et al (2001) The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294:1731\u20131735. https:\/\/doi.org\/10.1126\/science.1062960","journal-title":"Science"},{"key":"1267_CR16","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1161\/STROKEAHA.110.599118","volume":"42","author":"W Chen","year":"2011","unstructured":"Chen W, Ma Q, Suzuki H, Hartman R, Tang J, Zhang JH (2011) Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model. Stroke 42:764\u2013769. https:\/\/doi.org\/10.1161\/STROKEAHA.110.599118","journal-title":"Stroke"},{"key":"1267_CR17","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3389\/fimmu.2017.00321","volume":"8","author":"N Clemente","year":"2017","unstructured":"Clemente N, Comi C, Raineri D, Cappellano G, Vecchio D, Orilieri E, Gigliotti CL, Boggio E, Dianzani C, Sorosina M et al (2017) Role of anti-osteopontin antibodies in multiple sclerosis and experimental Autoimmune Encephalomyelitis. Front Immunol 8:321. https:\/\/doi.org\/10.3389\/fimmu.2017.00321","journal-title":"Front Immunol"},{"key":"1267_CR18","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.3233\/JAD-2010-1309","volume":"19","author":"C Comi","year":"2010","unstructured":"Comi C, Carecchio M, Chiocchetti A, Nicola S, Galimberti D, Fenoglio C, Cappellano G, Monaco F, Scarpini E, Dianzani U (2010) Osteopontin is increased in the cerebrospinal fluid of patients with Alzheimer\u2019s disease and its levels correlate with cognitive decline. J Alzheimers Dis 19:1143\u20131148. https:\/\/doi.org\/10.3233\/JAD-2010-1309","journal-title":"J Alzheimers Dis"},{"key":"1267_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1542\/peds.112.1.1","volume":"112","author":"SJ Counsell","year":"2003","unstructured":"Counsell SJ, Allsop JM, Harrison MC, Larkman DJ, Kennea NL, Kapellou O, Cowan FM, Hajnal JV, Edwards AD, Rutherford MA (2003) Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality. Pediatrics 112:1\u20137. https:\/\/doi.org\/10.1542\/peds.112.1.1","journal-title":"Pediatrics"},{"key":"1267_CR20","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1172\/JCI12980","volume":"107","author":"DT Denhardt","year":"2001","unstructured":"Denhardt DT, Noda M, O\u2019Regan AW, Pavlin D, Berman JS (2001) Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Investig 107:1055\u20131061. https:\/\/doi.org\/10.1172\/JCI12980","journal-title":"J Clin Investig"},{"key":"1267_CR21","doi-asserted-by":"publisher","unstructured":"Ellison JA, Velier JJ, Spera P, Jonak ZL, Wang X, Barone FC, Feuerstein GZ (1998) Osteopontin and its integrin receptor alpha(v)beta3 are upregulated during formation of the glial scar after focal stroke. Stroke 29: 1698\u20131706; discussion 1707 Doi https:\/\/doi.org\/10.1161\/01.str.29.8.1698","DOI":"10.1161\/01.str.29.8.1698"},{"key":"1267_CR22","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1002\/glia.22885","volume":"63","author":"M Gliem","year":"2015","unstructured":"Gliem M, Krammes K, Liaw L, van Rooijen N, Hartung HP, Jander S (2015) Macrophage-derived osteopontin induces reactive astrocyte polarization and promotes re-establishment of the blood brain barrier after ischemic stroke. Glia 63:2198\u20132207. https:\/\/doi.org\/10.1002\/glia.22885","journal-title":"Glia"},{"issue":"253\u2013271","key":"1267_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.11.004","volume":"50","author":"TR Hammond","year":"2019","unstructured":"Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, Walker AJ, Gergits F, Segel M, Nemesh J et al (2019) Single-Cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 50(253\u2013271):e256. https:\/\/doi.org\/10.1016\/j.immuni.2018.11.004","journal-title":"Immunity"},{"key":"1267_CR24","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1093\/jnen\/62.5.441","volume":"62","author":"RL Haynes","year":"2003","unstructured":"Haynes RL, Folkerth RD, Keefe RJ, Sung I, Swzeda LI, Rosenberg PA, Volpe JJ, Kinney HC (2003) Nitrosative and oxidative injury to premyelinating oligodendrocytes in periventricular leukomalacia. J Neuropath Exp Neur 62:441\u2013450. https:\/\/doi.org\/10.1093\/jnen\/62.5.441","journal-title":"J Neuropath Exp Neur"},{"key":"1267_CR25","doi-asserted-by":"publisher","first-page":"5910","DOI":"10.1523\/JNEUROSCI.22-14-05910.2002","volume":"22","author":"M Hedtjarn","year":"2002","unstructured":"Hedtjarn M, Leverin AL, Eriksson K, Blomgren K, Mallard C, Hagberg H (2002) Interleukin-18 involvement in hypoxic-ischemic brain injury. J Neurosci 22:5910\u20135919","journal-title":"J Neurosci"},{"key":"1267_CR26","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1097\/01.WCB.0000141559.17620.36","volume":"24","author":"M Hedtjarn","year":"2004","unstructured":"Hedtjarn M, Mallard C, Hagberg H (2004) Inflammatory gene profiling in the developing mouse brain after hypoxia-ischemia. J Cerebral Blood Flow metabol Offic J Int Soc Cerebral Blood Flow Metabol 24:1333\u20131351. https:\/\/doi.org\/10.1097\/01.WCB.0000141559.17620.36","journal-title":"J Cerebral Blood Flow metabol Offic J Int Soc Cerebral Blood Flow Metabol"},{"key":"1267_CR27","first-page":"87","volume":"20","author":"A Hirayama","year":"2001","unstructured":"Hirayama A, Okoshi Y, Hachiya Y, Ozawa Y, Ito M, Kida Y, Imai Y, Kohsaka S, Takashima S (2001) Early immunohistochemical detection of axonal damage and glial activation in extremely immature brains with periventricular leukomalacia. Clin Neuropathol 20:87\u201391","journal-title":"Clin Neuropathol"},{"key":"1267_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53414-9","author":"T Hyvarinen","year":"2019","unstructured":"Hyvarinen T, Hagman S, Ristola M, Sukki L, Veijula K, Kreutzer J, Kallio P, Narkilahti S (2019) Co-stimulation with IL-1 beta and TNF-alpha induces an inflammatory reactive astrocyte phenotype with neurosupportive characteristics in a human pluripotent stem cell model system. Sci Rep-Uk. https:\/\/doi.org\/10.1038\/s41598-019-53414-9","journal-title":"Sci Rep-Uk"},{"key":"1267_CR29","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1080\/01616412.2018.1517995","volume":"40","author":"H Ikeshima-Kataoka","year":"2018","unstructured":"Ikeshima-Kataoka H, Matsui Y, Uede T (2018) Osteopontin is indispensable for activation of astrocytes in injured mouse brain and primary culture. Neurol Res 40:1071\u20131079. https:\/\/doi.org\/10.1080\/01616412.2018.1517995","journal-title":"Neurol Res"},{"key":"1267_CR30","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1542\/peds.2004-0326","volume":"115","author":"TE Inder","year":"2005","unstructured":"Inder TE, Warfield SK, Wang H, Huppi PS, Volpe JJ (2005) Abnormal cerebral structure is present at term in premature infants. Pediatrics 115:286\u2013294. https:\/\/doi.org\/10.1542\/peds.2004-0326","journal-title":"Pediatrics"},{"key":"1267_CR31","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.4049\/jimmunol.168.5.2096","volume":"168","author":"M Jansson","year":"2002","unstructured":"Jansson M, Panoutsakopoulou V, Baker J, Klein L, Cantor H (2002) Cutting edge: Attenuated experimental autoimmune encephalomyelitis in eta-1\/osteopontin-deficient mice. J Immunol 168:2096\u20132099. https:\/\/doi.org\/10.4049\/jimmunol.168.5.2096","journal-title":"J Immunol"},{"key":"1267_CR32","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.535320","volume":"14","author":"M Jinnai","year":"2020","unstructured":"Jinnai M, Koning G, Singh-Mallah G, Jonsdotter A, Leverin AL, Svedin P, Nair S, Takeda S, Wang X, Mallard C et al (2020) A model of germinal matrix hemorrhage in preterm rat pups. Front Cell Neurosci 14:535320. https:\/\/doi.org\/10.3389\/fncel.2020.535320","journal-title":"Front Cell Neurosci"},{"key":"1267_CR33","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3389\/fncel.2020.00198","volume":"14","author":"AM Jurga","year":"2020","unstructured":"Jurga AM, Paleczna M, Kuter KZ (2020) Overview of general and discriminating markers of differential microglia phenotypes. Front Cell Neurosci 14:198. https:\/\/doi.org\/10.3389\/fncel.2020.00198","journal-title":"Front Cell Neurosci"},{"key":"1267_CR34","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1007\/s11481-015-9613-1","volume":"10","author":"D Klebe","year":"2015","unstructured":"Klebe D, McBride D, Flores JJ, Zhang JH, Tang J (2015) Modulating the immune response towards a neuroregenerative peri-injury milieu after cerebral hemorrhage. J Neuroimmune Pharmacol 10:576\u2013586. https:\/\/doi.org\/10.1007\/s11481-015-9613-1","journal-title":"J Neuroimmune Pharmacol"},{"key":"1267_CR35","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1007\/s00381-012-1897-3","volume":"28","author":"K Klebermass-Schrehof","year":"2012","unstructured":"Klebermass-Schrehof K, Czaba C, Olischar M, Fuiko R, Waldhoer T, Rona Z, Pollak A, Weninger M (2012) Impact of low-grade intraventricular hemorrhage on long-term neurodevelopmental outcome in preterm infants. Childs Nerv Syst 28:2085\u20132092. https:\/\/doi.org\/10.1007\/s00381-012-1897-3","journal-title":"Childs Nerv Syst"},{"key":"1267_CR36","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/s0166-2236(00)01581-2","volume":"23","author":"CY Kuan","year":"2000","unstructured":"Kuan CY, Roth KA, Flavell RA, Rakic P (2000) Mechanisms of programmed cell death in the developing brain. Trends Neurosci 23:291\u2013297. https:\/\/doi.org\/10.1016\/s0166-2236(00)01581-2","journal-title":"Trends Neurosci"},{"key":"1267_CR37","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/s0022-3476(99)70237-4","volume":"134","author":"K Kuban","year":"1999","unstructured":"Kuban K, Sanocka U, Leviton A, Allred EN, Pagano M, Dammann O, Share J, Rosenfeld D, Abiri M, DiSalvo D et al (1999) White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. The Developmental Epidemiology Network. J Pediatr 134:539\u2013546. https:\/\/doi.org\/10.1016\/s0022-3476(99)70237-4","journal-title":"J Pediatr"},{"key":"1267_CR38","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.expneurol.2012.04.003","volume":"236","author":"T Lekic","year":"2012","unstructured":"Lekic T, Manaenko A, Rolland W, Krafft PR, Peters R, Hartman RE, Altay O, Tang J, Zhang JH (2012) Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus. Exp Neurol 236:69\u201378. https:\/\/doi.org\/10.1016\/j.expneurol.2012.04.003","journal-title":"Exp Neurol"},{"key":"1267_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00330","author":"D Ley","year":"2016","unstructured":"Ley D, Romantsik O, Vallius S, Sveinsdottir K, Sveinsdottir S, Agyemang AA, Baumgarten M, Morgelin M, Lutay N, Bruschettini M et al (2016) High presence of extracellular hemoglobin in the periventricular white matter following preterm intraventricular hemorrhage. Front Physiol. https:\/\/doi.org\/10.3389\/fphys.2016.00330","journal-title":"Front Physiol"},{"issue":"207\u2013223","key":"1267_CR40","doi-asserted-by":"publisher","first-page":"e210","DOI":"10.1016\/j.neuron.2018.12.006","volume":"101","author":"Q Li","year":"2019","unstructured":"Li Q, Cheng Z, Zhou L, Darmanis S, Neff NF, Okamoto J, Gulati G, Bennett ML, Sun LO, Clarke LE et al (2019) Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-Cell RNA sequencing. Neuron 101(207\u2013223):e210. https:\/\/doi.org\/10.1016\/j.neuron.2018.12.006","journal-title":"Neuron"},{"key":"1267_CR41","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s12079-009-0068-0","volume":"3","author":"SA Lund","year":"2009","unstructured":"Lund SA, Giachelli CM, Scatena M (2009) The role of osteopontin in inflammatory processes. J Cell Commun Signal 3:311\u2013322. https:\/\/doi.org\/10.1007\/s12079-009-0068-0","journal-title":"J Cell Commun Signal"},{"key":"1267_CR42","doi-asserted-by":"publisher","first-page":"e0156245","DOI":"10.1371\/journal.pone.0156245","volume":"11","author":"M Martinez-Biarge","year":"2016","unstructured":"Martinez-Biarge M, Groenendaal F, Kersbergen KJ, Benders MJ, Foti F, Cowan FM, de Vries LS (2016) MRI based preterm white matter injury classification: the importance of sequential imaging in determining severity of injury. PLoS ONE 11:e0156245. https:\/\/doi.org\/10.1371\/journal.pone.0156245","journal-title":"PLoS ONE"},{"key":"1267_CR43","doi-asserted-by":"publisher","first-page":"134539","DOI":"10.1016\/j.neulet.2019.134539","volume":"714","author":"NB McNamara","year":"2020","unstructured":"McNamara NB, Miron VE (2020) Microglia in developing white matter and perinatal brain injury. Neurosci Lett 714:134539. https:\/\/doi.org\/10.1016\/j.neulet.2019.134539","journal-title":"Neurosci Lett"},{"key":"1267_CR44","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/glia.23936","volume":"69","author":"C Melero-Jerez","year":"2021","unstructured":"Melero-Jerez C, Fernandez-Gomez B, Lebron-Galan R, Ortega MC, Sanchez-de Lara I, Ojalvo AC, Clemente D, de Castro F (2021) Myeloid-derived suppressor cells support remyelination in a murine model of multiple sclerosis by promoting oligodendrocyte precursor cell survival, proliferation, and differentiation. Glia 69:905\u2013924. https:\/\/doi.org\/10.1002\/glia.23936","journal-title":"Glia"},{"key":"1267_CR45","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/sj.jcbfm.9600022","volume":"25","author":"R Meller","year":"2005","unstructured":"Meller R, Stevens SL, Minami M, Cameron JA, King S, Rosenzweig H, Doyle K, Lessov NS, Simon RP, Stenzel-Poore MP (2005) Neuroprotection by osteopontin in stroke. J Cerebral Blood Flow metabol Offic J Int Soc Cerebral Blood Flow Metabol 25:217\u2013225. https:\/\/doi.org\/10.1038\/sj.jcbfm.9600022","journal-title":"J Cerebral Blood Flow metabol Offic J Int Soc Cerebral Blood Flow Metabol"},{"key":"1267_CR46","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1523\/JNEUROSCI.13-04-01441.1993","volume":"13","author":"A Oka","year":"1993","unstructured":"Oka A, Belliveau MJ, Rosenberg PA, Volpe JJ (1993) Vulnerability of oligodendroglia to glutamate: pharmacology, mechanisms, and prevention. J Neurosci 13:1441\u20131453","journal-title":"J Neurosci"},{"key":"1267_CR47","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41390-020-0780-2","volume":"87","author":"A Parodi","year":"2020","unstructured":"Parodi A, Govaert P, Horsch S, Bravo MC, Ramenghi LA, eur USbg, (2020) Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome. Pediatr Res 87:13\u201324. https:\/\/doi.org\/10.1038\/s41390-020-0780-2","journal-title":"Pediatr Res"},{"key":"1267_CR48","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jneuroim.2016.09.009","volume":"299","author":"M Rabenstein","year":"2016","unstructured":"Rabenstein M, Vay SU, Flitsch LJ, Fink GR, Schroeter M, Rueger MA (2016) Osteopontin directly modulates cytokine expression of primary microglia and increases their survival. J Neuroimmunol 299:130\u2013138. https:\/\/doi.org\/10.1016\/j.jneuroim.2016.09.009","journal-title":"J Neuroimmunol"},{"key":"1267_CR49","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12974-019-1489-1","volume":"16","author":"TR Riew","year":"2019","unstructured":"Riew TR, Kim S, Jin X, Kim HL, Lee JH, Lee MY (2019) Osteopontin and its spatiotemporal relationship with glial cells in the striatum of rats treated with mitochondrial toxin 3-nitropropionic acid: possible involvement in phagocytosis. J Neuroinflammation 16:99. https:\/\/doi.org\/10.1186\/s12974-019-1489-1","journal-title":"J Neuroinflammation"},{"key":"1267_CR50","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1007\/Bf00686088","volume":"70","author":"U Roessmann","year":"1986","unstructured":"Roessmann U, Gambetti P (1986) Pathological reaction of astrocytes in perinatal brain injury - immunohistochemical study. Acta Neuropathol 70:302\u2013307. https:\/\/doi.org\/10.1007\/Bf00686088","journal-title":"Acta Neuropathol"},{"key":"1267_CR51","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1136\/adc.60.9.798","volume":"60","author":"DI Rushton","year":"1985","unstructured":"Rushton DI, Preston PR, Durbin GM (1985) Structure and evolution of echo dense lesions in the neonatal brain. A combined ultrasound and necropsy study. Arch Dis Child 60:798\u2013808. https:\/\/doi.org\/10.1136\/adc.60.9.798","journal-title":"Arch Dis Child"},{"key":"1267_CR52","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nn.3604","volume":"17","author":"N Salmaso","year":"2014","unstructured":"Salmaso N, Jablonska B, Scafidi J, Vaccarino FM, Gallo V (2014) Neurobiology of premature brain injury. Nat Neurosci 17:341\u2013346. https:\/\/doi.org\/10.1038\/nn.3604","journal-title":"Nat Neurosci"},{"key":"1267_CR53","doi-asserted-by":"publisher","first-page":"6943","DOI":"10.4049\/jimmunol.0900065","volume":"182","author":"L Schack","year":"2009","unstructured":"Schack L, Stapulionis R, Christensen B, Kofod-Olsen E, Sorensen UBS, Vorup-Jensen T, Sorensen ES, Hollsberg P (2009) Osteopontin enhances phagocytosis through a novel osteopontin receptor, the alpha(x)beta(2) Integrin. J Immunol 182:6943\u20136950. https:\/\/doi.org\/10.4049\/jimmunol.0900065","journal-title":"J Immunol"},{"key":"1267_CR54","doi-asserted-by":"publisher","first-page":"H2258","DOI":"10.1152\/ajpheart.1998.275.6.H2258","volume":"275","author":"JA Scott","year":"1998","unstructured":"Scott JA, Weir ML, Wilson SM, Xuan JW, Chambers AF, McCormack DG (1998) Osteopontin inhibits inducible nitric oxide synthase activity in rat vascular tissue. Am J Physiol 275:H2258-2265. https:\/\/doi.org\/10.1152\/ajpheart.1998.275.6.H2258","journal-title":"Am J Physiol"},{"key":"1267_CR55","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.mcn.2003.12.014","volume":"25","author":"R Selvaraju","year":"2004","unstructured":"Selvaraju R, Bernasconi L, Losberger C, Graber P, Kadi L, Avellana-Adalid V, Picard-Riera N, Baron Van Evercooren A, Cirillo R, Kosco-Vilbois M et al (2004) Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro. Mol Cell Neurosci 25:707\u2013721. https:\/\/doi.org\/10.1016\/j.mcn.2003.12.014","journal-title":"Mol Cell Neurosci"},{"key":"1267_CR56","doi-asserted-by":"publisher","unstructured":"Shi L, Sun Z, Su W, Xu F, Xie D, Zhang Q, Dai X, Iyer K, Hitchens TK, Foley LM et al. (2021) Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke. Immunity, https:\/\/doi.org\/10.1016\/j.immuni.2021.04.022","DOI":"10.1016\/j.immuni.2021.04.022"},{"key":"1267_CR57","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1002\/glia.21110","volume":"59","author":"YJ Shin","year":"2011","unstructured":"Shin YJ, Kim HL, Choi JS, Choi JY, Cha JH, Lee MY (2011) Osteopontin: correlation with phagocytosis by brain macrophages in a rat model of stroke. Glia 59:413\u2013423. https:\/\/doi.org\/10.1002\/glia.21110","journal-title":"Glia"},{"key":"1267_CR58","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/BF00686080","volume":"70","author":"K Skullerud","year":"1986","unstructured":"Skullerud K, Westre B (1986) Frequency and prognostic significance of germinal matrix hemorrhage, periventricular leukomalacia, and pontosubicular necrosis in preterm neonates. Acta Neuropathol 70:257\u2013261. https:\/\/doi.org\/10.1007\/BF00686080","journal-title":"Acta Neuropathol"},{"key":"1267_CR59","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","volume":"32","author":"MV Sofroniew","year":"2009","unstructured":"Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638\u2013647. https:\/\/doi.org\/10.1016\/j.tins.2009.08.002","journal-title":"Trends Neurosci"},{"key":"1267_CR60","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","volume":"119","author":"MV Sofroniew","year":"2010","unstructured":"Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7\u201335. https:\/\/doi.org\/10.1007\/s00401-009-0619-8","journal-title":"Acta Neuropathol"},{"key":"1267_CR61","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1001\/jama.2015.10244","volume":"314","author":"BJ Stoll","year":"2015","unstructured":"Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, Laptook AR, Sanchez PJ, Van Meurs KP, Wyckoff M et al (2015) Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993\u20132012. JAMA 314:1039\u20131051. https:\/\/doi.org\/10.1001\/jama.2015.10244","journal-title":"JAMA"},{"key":"1267_CR62","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/pr.2012.186","volume":"73","author":"V Supramaniam","year":"2013","unstructured":"Supramaniam V, Vontell R, Srinivasan L, Wyatt-Ashmead J, Hagberg H, Rutherford M (2013) Microglia activation in the extremely preterm human brain. Pediatr Res 73:301\u2013309. https:\/\/doi.org\/10.1038\/pr.2012.186","journal-title":"Pediatr Res"},{"key":"1267_CR63","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/j.1750-3639.2001.tb00381.x","volume":"11","author":"SL Tahraoui","year":"2001","unstructured":"Tahraoui SL, Marret S, Bodenant C, Leroux P, Dommergues MA, Evrard P, Gressens P (2001) Central role of microglia in neonatal excitotoxic lesions ef the murine periventricular white matter. Brain Pathol 11:56\u201371","journal-title":"Brain Pathol"},{"key":"1267_CR64","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1042\/Cbi20120172","volume":"36","author":"BR Tambuyzer","year":"2012","unstructured":"Tambuyzer BR, Casteleyn C, Vergauwen H, Van Cruchten S, Van Ginneken C (2012) Osteopontin alters the functional profile of porcine microglia in vitro. Cell Biol Int 36:1233\u20131238. https:\/\/doi.org\/10.1042\/Cbi20120172","journal-title":"Cell Biol Int"},{"key":"1267_CR65","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s004010051194","volume":"100","author":"F Tanaka","year":"2000","unstructured":"Tanaka F, Ozawa Y, Inage Y, Deguchi K, Itoh M, Imai Y, Kohsaka S, Takashima S (2000) Association of osteopontin with ischemic axonal death in periventricular leukomalacia. Acta Neuropathol 100:69\u201374. https:\/\/doi.org\/10.1007\/s004010051194","journal-title":"Acta Neuropathol"},{"key":"1267_CR66","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-12","author":"SG Torres-Platas","year":"2014","unstructured":"Torres-Platas SG, Comeau S, Rachalski A, Dal Bo G, Cruceanu C, Turecki G, Giros B, Mechawar N (2014) Morphometric characterization of microglial phenotypes in human cerebral cortex. J Neuroinflammation. https:\/\/doi.org\/10.1186\/1742-2094-11-12","journal-title":"J Neuroinflammation"},{"key":"1267_CR67","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/glia.23256","volume":"66","author":"E van Tilborg","year":"2018","unstructured":"van Tilborg E, de Theije CGM, van Hal M, Wagenaar N, de Vries LS, Benders MJ, Rowitch DH, Nijboer CH (2018) Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury. Glia 66:221\u2013238. https:\/\/doi.org\/10.1002\/glia.23256","journal-title":"Glia"},{"key":"1267_CR68","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1161\/STROKEAHA.110.608315","volume":"42","author":"CT van Velthoven","year":"2011","unstructured":"van Velthoven CT, Heijnen CJ, van Bel F, Kavelaars A (2011) Osteopontin enhances endogenous repair after neonatal hypoxic-ischemic brain injury. Stroke 42:2294\u20132301. https:\/\/doi.org\/10.1161\/STROKEAHA.110.608315","journal-title":"Stroke"},{"key":"1267_CR69","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.ecoenv.2019.01.005","volume":"171","author":"J Wang","year":"2019","unstructured":"Wang J, Huang J, Zhu M, Chen S, Chen C, Miao C, He H, Song Y (2019) Osteopontin potentiates PM-induced IL-1alpha and IL-1beta production via the ERK\/JNK signaling pathway. Ecotoxicol Environ Saf 171:467\u2013474. https:\/\/doi.org\/10.1016\/j.ecoenv.2019.01.005","journal-title":"Ecotoxicol Environ Saf"},{"key":"1267_CR70","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.cytogfr.2008.08.001","volume":"19","author":"KX Wang","year":"2008","unstructured":"Wang KX, Denhardt DT (2008) Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev 19:333\u2013345. https:\/\/doi.org\/10.1016\/j.cytogfr.2008.08.001","journal-title":"Cytokine Growth Factor Rev"},{"key":"1267_CR71","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1097\/NEN.0b013e3182496429","volume":"71","author":"C Verney","year":"2012","unstructured":"Verney C, Pogledic I, Biran V, Adle-Biassette H, Fallet-Bianco C, Gressens P (2012) Microglial reaction in axonal crossroads is a hallmark of noncystic periventricular white matter injury in very preterm infants. J Neuropath Exp Neur 71:251\u2013264. https:\/\/doi.org\/10.1097\/NEN.0b013e3182496429","journal-title":"J Neuropath Exp Neur"},{"key":"1267_CR72","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.pediatrneurol.2019.02.016","volume":"95","author":"JJ Volpe","year":"2019","unstructured":"Volpe JJ (2019) Dysmaturation of premature brain: importance, cellular mechanisms, and potential interventions. Pediatr Neurol 95:42\u201366. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2019.02.016","journal-title":"Pediatr Neurol"},{"key":"1267_CR73","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1159\/000346158","volume":"35","author":"R Vontell","year":"2013","unstructured":"Vontell R, Supramaniam V, Thornton C, Wyatt-Ashmead J, Mallard C, Gressens P, Rutherford M, Hagberg H (2013) Toll-like receptor 3 expression in glia and neurons alters in response to white matter injury in preterm infants. Dev Neurosci 35:130\u2013139. https:\/\/doi.org\/10.1159\/000346158","journal-title":"Dev Neurosci"},{"key":"1267_CR74","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1097\/NEN.0000000000000172","volume":"74","author":"R Vontell","year":"2015","unstructured":"Vontell R, Supramaniam V, Wyatt-Ashmead J, Gressens P, Rutherford M, Hagberg H, Thornton C (2015) Cellular mechanisms of toll-like receptor-3 activation in the thalamus are associated with white matter injury in the developing brain. J Neuropathol Exp Neurol 74:273\u2013285. https:\/\/doi.org\/10.1097\/NEN.0000000000000172","journal-title":"J Neuropathol Exp Neurol"},{"key":"1267_CR75","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1879437","author":"H Yu","year":"2017","unstructured":"Yu H, Liu XH, Zhong YS (2017) The effect of osteopontin on microglia. Biomed Res Int. https:\/\/doi.org\/10.1155\/2017\/1879437","journal-title":"Biomed Res Int"},{"key":"1267_CR76","doi-asserted-by":"publisher","unstructured":"Zhao C, Fancy SP, Ffrench-Constant C, Franklin RJ (2008) Osteopontin is extensively expressed by macrophages following CNS demyelination but has a redundant role in remyelination. Neurobiol Dis 31: 209-217 https:\/\/doi.org\/10.1016\/j.nbd.2008.04.","DOI":"10.1016\/j.nbd.2008.04"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-021-01267-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-021-01267-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-021-01267-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T20:40:04Z","timestamp":1634330404000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-021-01267-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,15]]},"references-count":76,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1267"],"URL":"https:\/\/doi.org\/10.1186\/s40478-021-01267-7","relation":{},"ISSN":["2051-5960"],"issn-type":[{"type":"electronic","value":"2051-5960"}],"subject":[],"published":{"date-parts":[[2021,10,15]]},"assertion":[{"value":"6 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed parental consent was acquired in accordance with the National Health Services (NHS) UK guidelines, and ethical approval was obtained from the National Research Ethics Services (West London), UK (ethic number: 07\/H0707\/139).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors have no conflict of interest for disclosure.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"166"}}