{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:36:02Z","timestamp":1780637762428,"version":"3.54.1"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS094570"],"award-info":[{"award-number":["R01NS094570"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Fluids Barriers CNS"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Approximately 30% of cerebrospinal fluid (CSF) shunt systems for hydrocephalus fail within the first year and 98% of all patients will have shunt failure in their lifetime. Obstruction remains the most common reason for shunt failure. Previous evidence suggests elevated pro-inflammatory cytokines in CSF are associated with worsening clinical outcomes in neuroinflammatory diseases. The aim of this study was to determine whether cytokines and matrix metalloproteinases (MMPs) contribute towards shunt failure in hydrocephalus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using multiplex ELISA, this study examined shunt failure through the CSF protein concentration profiles of select pro-inflammatory and anti-inflammatory cytokines, as well as select MMPs. Interdependencies such as the past number of previous revisions, length of time implanted, patient age, and obstruction or non-obstruction revision were examined. The pro-inflammatory cytokines were IL-1\u03b2, IL-2, IL-5, IL-6, IL-8, IL-12, IL-17, TNF-\u03b1, GM-CSF, IFN-\u03b3. The anti-inflammatory cytokines were IL-4 and IL-10, and the MMPs were MMP-2, MMP-3, MMP-7, MMP-9. Protein concentration is reported as pg\/mL for each analyte.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patient CSF was obtained at the time of shunt revision operation; all pediatric (&lt;\u200918), totaling n\u2009=\u200938. IL-10, IL-6, IL-8 and MMP-7 demonstrated significantly increased concentrations in patient CSF for the non-obstructed subgroup. Etiological examination revealed IL-6 was increased in both obstructed and non-obstructed cases for PHH and congenital hydrocephalic patients, while IL-8 was higher only in PHH patients. In terms of number of past revisions, IL-10, IL-6, IL-8, MMP-7 and MMP-9 progressively increased from zero to two past revisions and then remained low for subsequent revisions. This presentation was notably absent in the obstruction subgroup. Shunts implanted for three months or less showed significantly increased concentrations of IL-6, IL-8, and MMP-7 in the obstruction subgroup. Lastly, only patients aged six months or less presented with significantly increased concentration of IL-8 and MMP-7.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Non-obstructive cases are reported here to accompany significantly higher CSF cytokine and MMP protein levels compared to obstructive cases for IL-10, IL-6, IL-8, MMP-7 and MMP-9. A closer examination of the definition of obstruction and the role neuroinflammation plays in creating shunt obstruction in hydrocephalic patients is suggested.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12987-021-00237-4","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T07:18:20Z","timestamp":1611904700000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction"],"prefix":"10.1186","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-7457","authenticated-orcid":false,"given":"Carolyn A.","family":"Harris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego M.","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rooshan","family":"Arshad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"James P.","family":"McAllister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"David D.","family":"Limbrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"issue":"11","key":"237_CR1","first-page":"502","volume":"55","author":"R Rizvi","year":"2005","unstructured":"Rizvi R, Anjum Q. Hydrocephalus in children. J Pak Med Assoc. 2005;55(11):502\u20137.","journal-title":"J Pak Med Assoc"},{"key":"237_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-9-18","author":"M Vinchon","year":"2012","unstructured":"Vinchon M, et al. Pediatric hydrocephalus outcomes: a review. Fluids Barriers CNS. 2012. https:\/\/doi.org\/10.1186\/2045-8118-9-18.","journal-title":"Fluids Barriers CNS"},{"key":"237_CR3","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1542\/pir.2015-0134)","volume":"37","author":"Z Wright","year":"2016","unstructured":"Wright Z, et al. Pediatric hydrocephalus: current state of diagnosis and treatment. Pediatrics Rev. 2016;37:478\u201390. https:\/\/doi.org\/10.1542\/pir.2015-0134).","journal-title":"Pediatrics Rev"},{"key":"237_CR4","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1055\/s-0043-108550","volume":"189","author":"S Langner","year":"2017","unstructured":"Langner S, et al. Diagnosis and Differential Diagnosis of Hydrocephalus in Adults\u201d. \u201cDiagnostik und Differenzialdiagnostik des Hydrozephalus beim Erwachsenen. RoFo: Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin. 2017;189:728\u201339. https:\/\/doi.org\/10.1055\/s-0043-108550.","journal-title":"RoFo: Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin"},{"issue":"9","key":"237_CR5","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1007\/s00117-012-2327-y","volume":"52","author":"R Eymann","year":"2012","unstructured":"Eymann R. \u201cKlinische Symptome des Hydrozephalus\u201d [Clinical symptoms of hydrocephalus]. Der Radiologe. 2012;52(9):807\u201312. https:\/\/doi.org\/10.1007\/s00117-012-2327-y.","journal-title":"Der Radiologe"},{"key":"237_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0204926","author":"AM Isaacs","year":"2018","unstructured":"Isaacs AM, et al. Age-specific global epidemiology of hydrocephalus: systematic review, metanalysis and global birth surveillance. PLoS ONE. 2018. https:\/\/doi.org\/10.1371\/journal.pone.0204926.","journal-title":"PLoS ONE"},{"key":"237_CR7","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3171\/PED\/2008\/1\/2\/131","volume":"1","author":"TD Simon","year":"2008","unstructured":"Simon TD, et al. Hospital care for children with hydrocephalus in the United States: utilization, charges, comorbidities, and deaths. J Neurosurg. 2008;1:131\u20137. https:\/\/doi.org\/10.3171\/PED\/2008\/1\/2\/131.","journal-title":"J Neurosurg"},{"key":"237_CR8","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-61304-8","volume-title":"Hydrocephalus: what do we know? And what do we still not know?","author":"A Ammar","year":"2017","unstructured":"Ammar A. Hydrocephalus: what do we know? And what do we still not know? Berlin: Springer; 2017."},{"key":"237_CR9","doi-asserted-by":"publisher","DOI":"10.3171\/2017.10.JNS17439","author":"MC Dewan","year":"2018","unstructured":"Dewan MC, et al. Global hydrocephalus epidemiology and incidence: systematic review and meta-analysis. J Neurosurg. 2018. https:\/\/doi.org\/10.3171\/2017.10.JNS17439.","journal-title":"J Neurosurg"},{"key":"237_CR10","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1007\/s00381-016-3236-6","volume":"32","author":"AG Weil","year":"2016","unstructured":"Weil AG, et al. Efficacy and safety of endoscopic third ventriculostomy and choroid plexus cauterization for infantile hydrocephalus: a systematic review and meta-analysis. Childs Nerv Syst. 2016;32:2119\u201331. https:\/\/doi.org\/10.1007\/s00381-016-3236-6.","journal-title":"Childs Nerv Syst"},{"issue":"3","key":"237_CR11","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s00701-004-0444-8","volume":"147","author":"ON Gottfried","year":"2005","unstructured":"Gottfried ON, et al. Distal ventriculoperitoneal shunt failure secondary to Clostridium difficile colitis. Acta Neurochir. 2005;147(3):335\u20138. https:\/\/doi.org\/10.1007\/s00701-004-0444-8.","journal-title":"Acta Neurochir"},{"issue":"10\u201311","key":"237_CR12","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1007\/s003810000351","volume":"16","author":"JM Drake","year":"2000","unstructured":"Drake JM, et al. CSF shunts 50 years on\u2013past, present and future. Childs Nerv Syst. 2000;16(10\u201311):800\u20134. https:\/\/doi.org\/10.1007\/s003810000351.","journal-title":"Childs Nerv Syst"},{"issue":"1","key":"237_CR13","doi-asserted-by":"publisher","first-page":"S38","DOI":"10.4103\/2152-7806.109197","volume":"4","author":"BR Lutz","year":"2013","unstructured":"Lutz BR, et al. New and improved ways to treat hydrocephalus: pursuit of a smart shunt. Surg Neurol Int. 2013;4(1):S38-50. https:\/\/doi.org\/10.4103\/2152-7806.109197.","journal-title":"Surg Neurol Int"},{"issue":"1","key":"237_CR14","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S1042-3680(18)30281-X","volume":"9","author":"JP McAllister","year":"1998","unstructured":"McAllister JP, Chovan P. Neonatal hydrocephalus. Mechanisms and consequences. Neurosurg Clin N Am. 1998;9(1):73\u201393.","journal-title":"Neurosurg Clin N Am"},{"issue":"4","key":"237_CR15","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1227\/NEU.0b013e318208f360","volume":"68","author":"AM Korinek","year":"2011","unstructured":"Korinek AM, et al. Morbidity of ventricular cerebrospinal fluid shunt surgery in adults: an 8-year study. Neurosurgery. 2011;68(4):985\u201394. https:\/\/doi.org\/10.1227\/NEU.0b013e318208f360.","journal-title":"Neurosurgery"},{"issue":"6","key":"237_CR16","doi-asserted-by":"publisher","first-page":"633","DOI":"10.3171\/2015.5.PEDS14532","volume":"16","author":"AH Paulsen","year":"2015","unstructured":"Paulsen AH, et al. Pediatric hydrocephalus: 40-year outcomes in 128 hydrocephalic patients treated with shunts during childhood. Assessment of surgical outcome, work participation, and health-related quality of life. J Neurosurg. 2015;16(6):633\u201341. https:\/\/doi.org\/10.3171\/2015.5.PEDS14532.","journal-title":"J Neurosurg"},{"issue":"2","key":"237_CR17","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.wneu.2013.01.096","volume":"81","author":"GK Reddy","year":"2014","unstructured":"Reddy GK, et al. Long-term outcomes of ventriculoperitoneal shunt surgery in patients with hydrocephalus. World Neurosurg. 2014;81(2):404\u201310. https:\/\/doi.org\/10.1016\/j.wneu.2013.01.096.","journal-title":"World Neurosurg"},{"issue":"6","key":"237_CR18","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1159\/000452840","volume":"52","author":"BW Hanak","year":"2017","unstructured":"Hanak BW, et al. Cerebrospinal fluid shunting complications in children. Pediatric Neurosurg. 2017;52(6):381\u2013400. https:\/\/doi.org\/10.1159\/000452840.","journal-title":"Pediatric Neurosurg"},{"issue":"3","key":"237_CR19","doi-asserted-by":"publisher","first-page":"411","DOI":"10.3171\/jns.1982.56.3.0411","volume":"56","author":"LN Sekhar","year":"1982","unstructured":"Sekhar LN, et al. Malfunctioning ventriculoperitoneal shunts. Clinical and pathological features. J Neurosurg. 1982;56(3):411\u20136. https:\/\/doi.org\/10.3171\/jns.1982.56.3.0411.","journal-title":"J Neurosurg"},{"issue":"6","key":"237_CR20","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1227\/NEU.0b013e318244695f","volume":"70","author":"CA Harris","year":"2012","unstructured":"Harris CA, McAllister JP II. What we should know about the cellular and tissue response causing catheter obstruction in the treatment of hydrocephalus. Neurosurgery. 2012;70(6):1589\u2013601. https:\/\/doi.org\/10.1227\/NEU.0b013e318244695f.","journal-title":"Neurosurgery"},{"issue":"2","key":"237_CR21","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3171\/2016.2.PEDS15531","volume":"18","author":"BW Hanak","year":"2016","unstructured":"Hanak BW, et al. Toward a better understanding of the cellular basis for cerebrospinal fluid shunt obstruction: report on the construction of a bank of explanted hydrocephalus devices. J Neurosurg. 2016;18(2):213\u201323. https:\/\/doi.org\/10.3171\/2016.2.PEDS15531.","journal-title":"J Neurosurg"},{"issue":"7","key":"237_CR22","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/35081571","volume":"2","author":"VW Yong","year":"2001","unstructured":"Yong VW, et al. Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci. 2001;2(7):502\u201311. https:\/\/doi.org\/10.1038\/35081571.","journal-title":"Nat Rev Neurosci"},{"issue":"9","key":"237_CR23","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1177\/0271678X16655551","volume":"36","author":"RG Rempe","year":"2016","unstructured":"Rempe RG, et al. Matrix metalloproteinases in the brain and blood-brain barrier: versatile breakers and makers. J Cereb Blood Flow Metab. 2016;36(9):1481\u2013507. https:\/\/doi.org\/10.1177\/0271678X16655551.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"3","key":"237_CR24","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1089\/neu.2007.0438","volume":"25","author":"F Yu","year":"2008","unstructured":"Yu F, et al. Induction of mmp-9 expression and endothelial injury by oxidative stress after spinal cord injury. J Neurotrauma. 2008;25(3):184\u201395. https:\/\/doi.org\/10.1089\/neu.2007.0438.","journal-title":"J Neurotrauma"},{"key":"237_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2015.00019","author":"D Singh","year":"2015","unstructured":"Singh D, et al. Multifaceted role of matrix metalloproteinases (MMPs). Front Mol Biosci. 2015. https:\/\/doi.org\/10.3389\/fmolb.2015.00019.","journal-title":"Front Mol Biosci"},{"issue":"1","key":"237_CR26","doi-asserted-by":"publisher","first-page":"18075","DOI":"10.1038\/s41598-020-75233-z","volume":"10","author":"K Minta","year":"2020","unstructured":"Minta K, et al. Dynamics of cerebrospinal fluid levels of matrix metalloproteinases in human traumatic brain injury. Sci Rep. 2020;10(1):18075. https:\/\/doi.org\/10.1038\/s41598-020-75233-z.","journal-title":"Sci Rep"},{"key":"237_CR27","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.matbio.2017.11.007","volume":"75\u201376","author":"M-J Hannocks","year":"2019","unstructured":"Hannocks M-J, et al. The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes. Matrix Biol. 2019;75\u201376:102\u201313. https:\/\/doi.org\/10.1016\/j.matbio.2017.11.007.","journal-title":"Matrix Biol"},{"issue":"22","key":"237_CR28","doi-asserted-by":"publisher","first-page":"13055","DOI":"10.1074\/jbc.271.22.13055","volume":"271","author":"S Ye","year":"1996","unstructured":"Ye S, et al. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. The Journal of biological chemistry. 1996;271(22):13055\u201360. https:\/\/doi.org\/10.1074\/jbc.271.22.13055.","journal-title":"The Journal of biological chemistry"},{"key":"237_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-017-0083-0","author":"G Habiyaremye","year":"2017","unstructured":"Habiyaremye G, et al. Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus. Fluids Barriers CNS. 2017. https:\/\/doi.org\/10.1186\/s12987-017-0083-0.","journal-title":"Fluids Barriers CNS"},{"issue":"1","key":"237_CR30","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3171\/jns.1975.42.1.0061","volume":"42","author":"DB Shurtleff","year":"1975","unstructured":"Shurtleff DB, et al. Follow-up comparison of hydrocephalus with and without myelomeningocele. J Neurosurg. 1975;42(1):61\u20138. https:\/\/doi.org\/10.3171\/jns.1975.42.1.0061.","journal-title":"J Neurosurg"},{"issue":"5","key":"237_CR31","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1159\/000058428","volume":"36","author":"MJ McGirt","year":"2002","unstructured":"McGirt MJ, et al. Cerebrospinal fluid shunt survival and etiology of failures: a seven-year institutional experience. Pediatric Neurosurg. 2002;36(5):248\u201355. https:\/\/doi.org\/10.1159\/000058428.","journal-title":"Pediatric Neurosurg"},{"issue":"3","key":"237_CR32","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.neulet.2009.09.043","volume":"466","author":"R Mlekusch","year":"2009","unstructured":"Mlekusch R, Humpel C. Matrix metalloproteinases-2 and -3 are reduced in cerebrospinal fluid with low beta-amyloid1-42 levels. Neurosci Lett. 2009;466(3):135\u20138. https:\/\/doi.org\/10.1016\/j.neulet.2009.09.043.","journal-title":"Neurosci Lett"},{"key":"237_CR33","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.tube.2016.06.001","volume":"102","author":"J Wu","year":"2017","unstructured":"Wu J, et al. Multiple cytokine responses in discriminating between active tuberculosis and latent tuberculosis infection. Tuberculosis. 2017;102:68\u201375. https:\/\/doi.org\/10.1016\/j.tube.2016.06.001.","journal-title":"Tuberculosis"},{"issue":"2","key":"237_CR34","doi-asserted-by":"publisher","first-page":"e0192516","DOI":"10.1371\/journal.pone.0192516","volume":"13","author":"P de Flon","year":"2018","unstructured":"de Flon P, et al. Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls. PLoS ONE. 2018;13(2):e0192516. https:\/\/doi.org\/10.1371\/journal.pone.0192516.","journal-title":"PLoS ONE"},{"key":"237_CR35","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.011973","author":"DM Morales","year":"2012","unstructured":"Morales DM, et al. Alterations in protein regulators of neurodevelopment in the cerebrospinal fluid of infants with posthemorrhagic hydrocephalus of prematurity. Mol Cell Proteom. 2012. https:\/\/doi.org\/10.1074\/mcp.M111.011973.","journal-title":"Mol Cell Proteom"},{"key":"237_CR36","doi-asserted-by":"publisher","DOI":"10.5114\/fn.2017.72389","author":"K Czubowicz","year":"2017","unstructured":"Czubowicz K, et al. Levels of selected pro- and anti-inflammatory cytokines in cerebrospinal fluid in patients with hydrocephalus. Folia Neuropathol. 2017. https:\/\/doi.org\/10.5114\/fn.2017.72389.","journal-title":"Folia Neuropathol"},{"issue":"9","key":"237_CR37","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.7150\/ijbs.4679","volume":"8","author":"M Erta","year":"2012","unstructured":"Erta M, et al. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci. 2012;8(9):1254\u201366. https:\/\/doi.org\/10.7150\/ijbs.4679.","journal-title":"Int J Biol Sci"},{"issue":"23","key":"237_CR38","doi-asserted-by":"publisher","first-page":"13632","DOI":"10.1073\/pnas.2234031100","volume":"100","author":"CT Ekdahl","year":"2003","unstructured":"Ekdahl CT, et al. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA. 2003;100(23):13632\u20137. https:\/\/doi.org\/10.1073\/pnas.2234031100.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"237_CR39","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1111\/j.1471-4159.2009.05886","volume":"108","author":"NP Whitney","year":"2009","unstructured":"Whitney NP, et al. Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders. J Neurochem. 2009;108(6):1343\u201359. https:\/\/doi.org\/10.1111\/j.1471-4159.2009.05886.","journal-title":"J Neurochem"},{"issue":"5","key":"237_CR40","first-page":"1685","volume":"149","author":"LH Villarete","year":"1996","unstructured":"Villarete LH, Remick DG. Transcriptional and post-transcriptional regulation of interleukin-8. Am J Pathol. 1996;149(5):1685\u201393.","journal-title":"Am J Pathol"},{"issue":"2","key":"237_CR41","first-page":"201","volume":"1","author":"M Meem","year":"2011","unstructured":"Meem M, et al. Biomarkers for diagnosis of neonatal infections: a systematic analysis of their potential as a point-of-care diagnostics. J Global Health. 2011;1(2):201\u20139.","journal-title":"J Global Health"},{"key":"237_CR42","doi-asserted-by":"crossref","unstructured":"Strle K, et al. lnterleukin-10 in the Brain. Crit Rev. 2001;21(5).","DOI":"10.1615\/CritRevImmunol.v21.i5.20"},{"key":"237_CR43","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/nri2711","volume":"10","author":"M Saraiva","year":"2010","unstructured":"Saraiva M, et al. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10:170\u201381. https:\/\/doi.org\/10.1038\/nri2711.","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"237_CR44","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1007\/s11357-013-9518-y","volume":"35","author":"AA Willette","year":"2013","unstructured":"Willette AA, et al. Interleukin-8 and interleukin-10, brain volume and microstructure, and the influence of calorie restriction in old rhesus macaques. Age. 2013;35(6):2215\u201327. https:\/\/doi.org\/10.1007\/s11357-013-9518-y.","journal-title":"Age"},{"issue":"5548","key":"237_CR45","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1126\/science.1065057","volume":"294","author":"R Lee","year":"2001","unstructured":"Lee R, et al. Regulation of cell survival by secreted proneurotrophins. Science. 2001;294(5548):1945\u20138. https:\/\/doi.org\/10.1126\/science.1065057.","journal-title":"Science"},{"issue":"12","key":"237_CR46","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.1634\/stemcells.2008-0519","volume":"26","author":"BZ Barkho","year":"2008","unstructured":"Barkho BZ, et al. Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines. Stem Cells. 2008;26(12):3139\u201349. https:\/\/doi.org\/10.1634\/stemcells.2008-0519.","journal-title":"Stem Cells"},{"issue":"8","key":"237_CR47","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1523\/JNEUROSCI.1880-05.2006","volume":"26","author":"PH Larsen","year":"2006","unstructured":"Larsen PH, et al. Myelin formation during development of the CNS is delayed in matrix metalloproteinase-9 and -12 null mice. J Neurosci. 2006;26(8):2207\u201314. https:\/\/doi.org\/10.1523\/JNEUROSCI.1880-05.2006.","journal-title":"J Neurosci"},{"issue":"25","key":"237_CR48","doi-asserted-by":"publisher","first-page":"14657","DOI":"10.1074\/jbc.271.25.14657","volume":"271","author":"A Ito","year":"1996","unstructured":"Ito A, et al. Degradation of interleukin 1beta by matrix metalloproteinases. J Biol Chem. 1996;271(25):14657\u201360. https:\/\/doi.org\/10.1074\/jbc.271.25.14657.","journal-title":"J Biol Chem"},{"issue":"4","key":"237_CR49","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1227\/01.NEU.0000351768.11363.48","volume":"65","author":"M Grossetete","year":"2009","unstructured":"Grossetete M, et al. Elevation of matrix metalloproteinases 3 and 9 in cerebrospinal fluid and blood in patients with severe traumatic brain injury. Neurosurgery. 2009;65(4):702\u20138. https:\/\/doi.org\/10.1227\/01.NEU.0000351768.11363.48.","journal-title":"Neurosurgery"},{"issue":"5","key":"237_CR50","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1002\/jnr.10326","volume":"69","author":"J Zechel","year":"2002","unstructured":"Zechel J, et al. Alterations in matrix metalloproteinase-9 levels and tissue inhibitor of matrix metalloproteinases-1 expression in a transforming growth factor-beta transgenic model of hydrocephalus. J Neurosci Res. 2002;69(5):662\u20138. https:\/\/doi.org\/10.1002\/jnr.10326.","journal-title":"J Neurosci Res"},{"issue":"2","key":"237_CR51","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.earlhumdev.2007.08.006","volume":"84","author":"T Okamoto","year":"2008","unstructured":"Okamoto T, et al. Matrix metalloproteinases in infants with posthemorrhagic hydrocephalus. Early Human Dev. 2008;84(2):137\u20139. https:\/\/doi.org\/10.1016\/j.earlhumdev.2007.08.006.","journal-title":"Early Human Dev"}],"container-title":["Fluids and Barriers of the CNS"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12987-021-00237-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12987-021-00237-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12987-021-00237-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T07:22:00Z","timestamp":1611904920000},"score":1,"resource":{"primary":{"URL":"https:\/\/fluidsbarrierscns.biomedcentral.com\/articles\/10.1186\/s12987-021-00237-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,29]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["237"],"URL":"https:\/\/doi.org\/10.1186\/s12987-021-00237-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-78728\/v1","asserted-by":"object"}]},"ISSN":["2045-8118"],"issn-type":[{"value":"2045-8118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,29]]},"assertion":[{"value":"4 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"4"}}