{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:45:27Z","timestamp":1790401527495,"version":"4.1.0"},"reference-count":124,"publisher":"MDPI AG","issue":"10","license":[{"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\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: The present manuscript aims to be a narrative review evaluating the association between inflammation in chorioamnionitis and damage on respiratory centers, peripheral airways, and lungs, explaining the pathways responsible for apnea in preterm babies born by delivery after chorioamnionitis. Methods: A combination of keywords and MESH words was used, including: \u201cinflammation\u201d, \u201cchorioamnionitis\u201d, \u201cbrainstem\u201d, \u201ccytokines storm\u201d, \u201cpreterm birth\u201d, \u201cneonatal apnea\u201d, and \u201capnea physiopathology\u201d. All identified papers were screened for title and abstracts by the two authors to verify whether they met the proper criteria to write the topic. Results: Chorioamnionitis is usually associated with Fetal Inflammatory Response Syndrome (FIRS), resulting in injury of brain and lungs. Literature data have shown that infections causing chorioamnionitis are mostly associated with inflammation and consequent hypoxia-mediated brain injury. Moreover, inflammation and infection induce apneic episodes in neonates, as well as in animal samples. Chorioamnionitis-induced inflammation favors the systemic secretion of pro-inflammatory cytokines that are involved in abnormal development of the respiratory centers in the brainstem and in alterations of peripheral airways and lungs. Conclusions: Preterm birth shows a suboptimal development of the brainstem and abnormalities and altered development of peripheral airways and lungs. These alterations are responsible for reduced respiratory control and apnea. To date, mostly animal studies have been published. Therefore, more clinical studies on the role of chorioamninitis-induced inflammation on prematurity and neonatal apnea are necessary.<\/jats:p>","DOI":"10.3390\/children8100917","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T13:35:47Z","timestamp":1634304947000},"page":"917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Chorioamnionitis, Inflammation and Neonatal Apnea: Effects on Preterm Neonatal Brainstem and on Peripheral Airways: Chorioamnionitis and Neonatal Respiratory Functions"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4181-6287","authenticated-orcid":false,"given":"Giovanna","family":"Vitaliti","sequence":"first","affiliation":[{"name":"Unit of Pediatrics, Department of Medical Sciences, Section of Pediatrics, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4482-3506","authenticated-orcid":false,"given":"Raffaele","family":"Falsaperla","sequence":"additional","affiliation":[{"name":"Pediatrics and Pediatric Emergency Operative Unit, Azienda Ospedaliero Universitaria Policlinico G.Rodolico-San Marco, San Marco Hospital, University of Catania, 95124 Catania, Italy"},{"name":"Neonatal Intensive Care Unit, Azienda Ospedaliero Universitaria Policlinico G.Rodolico-San Marco, San Marco Hospital, San Marco Hospital, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/S0140-6736(12)60560-1","article-title":"Global, regional, and national causes of child mortality: An updated systematic analysis for 2010 with time trends since 2000","volume":"379","author":"Liu","year":"2012","journal-title":"Lancet"},{"key":"ref_2","unstructured":"World Health Organization (2012). Born Too Soon: The Global Action Report on Preterm Birth, World Health Organization."},{"key":"ref_3","first-page":"1404","article-title":"Preterm birth","volume":"2011","author":"Haas","year":"2011","journal-title":"BMJ Clin. Evid."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"229.e1","DOI":"10.1016\/j.ajog.2006.10.900","article-title":"Chorioamnionitis and fetal response in stillbirth","volume":"196","author":"Lahra","year":"2007","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fncel.2018.00026","article-title":"The Consequences of Preterm Birth and Chorioamnionitis on Brainstem Respiratory Centers: Implications for Neurochemical Development and Altered Functions by Inflammation and Prostaglandins","volume":"12","author":"Stojanovska","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Falsaperla, R., Vitaliti, G., Mailo, J., Corsello, G., and Ruggieri, M. (2021). Is autonomic nervous system involved in the epileptogenesis in preterm neonates?. Matern. Fetal Med., 11, in press.","DOI":"10.1097\/FM9.0000000000000105"},{"key":"ref_7","first-page":"147","article-title":"Cardiopulmonary changes with aeration of the newborn lung","volume":"16","author":"Hooper","year":"2015","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.clp.2012.09.009","article-title":"Physiology of transition from intrauterine to extrauterine life","volume":"39","author":"Hillman","year":"2012","journal-title":"Clin. Perinatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.tins.2012.11.004","article-title":"Brainstem respiratory networks: Building blocks and microcircuits","volume":"36","author":"Smith","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1183\/20734735.000716","article-title":"Common respiratory conditions of the newborn","volume":"12","author":"Gallacher","year":"2016","journal-title":"Breathe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/pr.2014.40","article-title":"Respiratory support for premature neonates in the delivery room: Effects on cardiovascular function and the development of brain injury","volume":"75","author":"Polglase","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.4187\/respcare.05384","article-title":"Randomized Comparison of Helmet CPAP Versus High-Flow Nasal Cannula Oxygen in Pediatric Respiratory Distress","volume":"62","author":"Vitaliti","year":"2017","journal-title":"Respir. Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jsgi.2006.02.011","article-title":"Chronic exposure to intra-amniotic lipopolysaccharide affects the ovine fetal brain","volume":"13","author":"Nitsos","year":"2006","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.siny.2006.03.004","article-title":"Inflammation and bronchopulmonary dysplasia: A continuing story","volume":"11","author":"Speer","year":"2006","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/AOG.0b013e3181e90046","article-title":"Chorioamnionitis and cerebral palsy: A meta-analysis","volume":"116","author":"Shatrov","year":"2010","journal-title":"Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.clp.2014.10.011","article-title":"Chorioamnionitis: Implication for the neonate","volume":"42","author":"Ericson","year":"2015","journal-title":"Clin. Perinatol."},{"key":"ref_17","first-page":"S29","article-title":"Acute chorioamnionitis and funisitis: Definition, pathologic features, and clinical significance","volume":"213","author":"Kim","year":"2015","journal-title":"Exp. Rev. Obstetr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1093\/infdis\/jiv587","article-title":"Placental infection with ureaplasma species is associated with histologic chorioamnionitis and adverse outcomes in moderately preterm and late-preterm infants","volume":"213","author":"Sweeney","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1055\/s-0033-1361823","article-title":"Fetal immune response to chorioamnionitis","volume":"32","author":"Kallapur","year":"2014","journal-title":"Semin. Reprod. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"412831","DOI":"10.1155\/2013\/412831","article-title":"The consequences of chorioamnionitis: Preterm birth and effects on development","volume":"2013","author":"Galinsky","year":"2013","journal-title":"J. Pregnancy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1542\/peds.110.4.673","article-title":"Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants","volume":"110","author":"Shalak","year":"2002","journal-title":"Pediatrics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1001\/archpedi.157.1.26","article-title":"Intrauterine exposure to infection and risk of cerebral palsy in very preterm infants","volume":"157","author":"Grether","year":"2003","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1341-8076.2005.00266.x","article-title":"Expression of inducible nitric oxide synthase and cyclooxygenase-2 mRNA in brain damage induced by lipopolysaccharide and intermittent hypoxia-ischemia in neonatal rats","volume":"31","author":"Yang","year":"2005","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1055\/s-0031-1295654","article-title":"Chorioamnionitis and chronic lung disease of prematurity: A path analysis of causality","volume":"29","author":"Dessardo","year":"2012","journal-title":"Am. J. Perinatol."},{"key":"ref_25","first-page":"56","article-title":"Association of respiratory distress syndrome and perinatal hypoxia with histologic chorioamnionitis in preterm infants","volume":"56","author":"Ecevit","year":"2014","journal-title":"Turk. J. Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/S0140-6736(95)92471-X","article-title":"Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies","volume":"346","author":"Murphy","year":"1995","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1001\/jama.290.20.2677","article-title":"Chorioamnionitis and cerebral palsy in term and near-term infants","volume":"290","author":"Wu","year":"2003","journal-title":"JAMA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"130","DOI":"10.4103\/jpn.JPN_185_16","article-title":"Pediatric Autoimmune Encephalitis","volume":"12","author":"Barbagallo","year":"2017","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E52","DOI":"10.1542\/peds.105.4.e52","article-title":"Adverse effects of nicotine and interleukin-1\u03b2 on autoresuscitation after apnea in piglets: Implications for sudden infant death syndrome","volume":"105","author":"Akre","year":"2000","journal-title":"Pediatrics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s12098-009-0199-6","article-title":"Non-rotavirus infection causing apnea in a neonate","volume":"76","author":"Kamaluddeen","year":"2009","journal-title":"Indian J. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.autneu.2010.03.012","article-title":"Autonomic dysfunction with early respiratory syncytial virus-related infection","volume":"156","author":"Stock","year":"2010","journal-title":"Auton. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.resp.2011.06.026","article-title":"An inflammatory pathway to apnea and autonomic dysregulation","volume":"178","author":"Herlenius","year":"2011","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/glia.22951","article-title":"Microglia modulate respiratory rhythm generation and autoresuscitation","volume":"64","author":"Morales","year":"2016","journal-title":"Glia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1128\/CMR.17.3.638-680.2004","article-title":"Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants","volume":"17","author":"Kaufman","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/S0140-6736(08)60798-9","article-title":"Infection and sudden unexpected death in infancy: A systematic retrospective case review","volume":"371","author":"Weber","year":"2008","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1007\/s00431-011-1409-6","article-title":"Apnea of prematurity: From cause to treatment","volume":"170","author":"Zhao","year":"2011","journal-title":"Eur. J. Pediatr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1128\/CMR.00031-13","article-title":"Early-onset neonatal sepsis","volume":"27","author":"Simonsen","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"737","DOI":"10.5665\/sleep.5618","article-title":"Perinatal risk factors associated with the obstructive sleep apnea syndrome in school-aged children born preterm","volume":"39","author":"Tapia","year":"2016","journal-title":"Sleep"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00404-012-2339-x","article-title":"Antenatal corticosteroids for fetal lung maturation in threatened preterm delivery: Indications and administration","volume":"286","author":"Surbek","year":"2012","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1177\/1753495X15601772","article-title":"Antenatal steroids for fetal lung maturity: Time to target more frequent doses to fewer women?","volume":"8","author":"Freeman","year":"2015","journal-title":"Obstet. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1542\/peds.2006-2174","article-title":"Auditory neural maturation after exposure to multiple courses of antenatal betamethasone in premature infants as evaluated by auditory brainstem response","volume":"119","author":"Amin","year":"2007","journal-title":"Pediatrics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/sj.jp.7210898","article-title":"Brainstem maturation after antenatal steroids exposure in premature infants as evaluated by auditory brainstem-evoked response","volume":"23","author":"Amin","year":"2003","journal-title":"J. Perinatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ntt.2011.09.004","article-title":"Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats","volume":"34","author":"Church","year":"2012","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_44","first-page":"213","article-title":"Effect of corticosteroids on brain growth in fetal sheep","volume":"94","author":"Huang","year":"1999","journal-title":"Obstet. Gynecol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Barton, S.K., Moss, T.J., Hooper, S.B., Crossley, K.J., Gill, A.W., Kluckow, M., Zahra, V., Wong, F.Y., Pichler, G., and Galinsky, R. (2014). Protective ventilation of preterm lambs exposed to acute chorioamnionitis does not reduce ventilation-induced lung or brain injury. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112402"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/molehr\/gav005","article-title":"Intra-amniotic pharmacological blockade of inflammatory signalling pathways in an ovine chorioamnionitis model","volume":"21","author":"Ireland","year":"2015","journal-title":"Mol. Hum. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1146\/annurev.pharmtox.43.100901.135729","article-title":"Innate immune responses to microbial poisons: Discovery and function of the Toll-like receptors","volume":"43","author":"Beutler","year":"2003","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1365-2567.2004.01976.x","article-title":"Signal transduction by the lipopolysaccharide receptor, toll-like receptor-4","volume":"113","year":"2004","journal-title":"Immunology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1165\/ajrcmb.17.1.f132","article-title":"The role of nuclear factor-\u03baB in cytokine gene regulation","volume":"17","author":"Blackwell","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"38658","DOI":"10.1074\/jbc.M106599200","article-title":"Positive and negative regulation of NF-\u03baB by COX-2: Roles of different prostaglandins","volume":"276","author":"Poligone","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.lfs.2003.10.042","article-title":"iNOS-mediated nitric oxide production and its regulation","volume":"75","author":"Aktan","year":"2004","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/jnr.20767","article-title":"Toll-like receptors in central nervous system glial inflammation and homeostasis","volume":"83","author":"Kielian","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1651-2227.2011.02564.x","article-title":"Intrapulmonary lipopolysaccharide exposure upregulates cytokine expression in the neonatal brainstem","volume":"101","author":"Balan","year":"2012","journal-title":"Acta Paediatr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"987.4","DOI":"10.1096\/fasebj.30.1_supplement.987.4","article-title":"Disturbances in central respiratory rhythm generation may contribute to breathing disturbances in prematurely born mice","volume":"30","author":"Ramirez","year":"2016","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neuropharm.2014.10.027","article-title":"Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability","volume":"96","author":"Vezzani","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.yfrne.2011.12.002","article-title":"Cytokines and brain excitability","volume":"33","author":"Galic","year":"2012","journal-title":"Front. Neuroendocrinol."},{"key":"ref_58","first-page":"497","article-title":"Interleukin-1\u03b2 inhibits \u03b3-aminobutyric acid type A (GABAA) receptor current in cultured hippocampal neurons","volume":"292","author":"Wang","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_59","first-page":"150","article-title":"Interleukin-6 protects cerebellar granule neurons from NMDA-induced neurotoxicity","volume":"59","author":"Wang","year":"2007","journal-title":"Sheng Li Xue Bao"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1126\/science.1067859","article-title":"Control of synaptic strength by glial TNF\u03b1","volume":"295","author":"Beattie","year":"2002","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1460-9568.2010.07342.x","article-title":"Role of immune molecules in the establishment and plasticity of glutamatergic synapses","volume":"32","author":"Fourgeaud","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jneuroim.2004.06.014","article-title":"Interleukin-6 produces neuronal loss in developing cerebellar granule neuron cultures","volume":"155","author":"Conroy","year":"2004","journal-title":"J. Neuroimmunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1046\/j.1460-9568.2000.00011.x","article-title":"Interleukin-6 inhibits neurotransmitter release and the spread of excitation in the rat cerebral cortex","volume":"12","author":"Tancredi","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1111\/j.1460-9568.2007.05615.x","article-title":"Chronic interleukin-6 alters the level of synaptic proteins in hippocampus in culture and In Vivo","volume":"25","author":"Vereyken","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1523\/JNEUROSCI.3338-07.2008","article-title":"Cytokine mechanisms of central sensitization: Distinct and overlapping role of interleukin-1\u03b2, interleukin-6, and tumor necrosis factor-\u03b1 in regulating synaptic and neuronal activity in the superficial spinal cord","volume":"28","author":"Kawasaki","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.resp.2011.06.017","article-title":"Systemic inflammation impairs respiratory chemoreflexes and plasticity","volume":"178","author":"Huxtable","year":"2011","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/jappl.1991.70.1.1","article-title":"Glutamic acid and \u03b3-aminobutyric acid neurotransmitters in central control of breathing","volume":"70","author":"Kazemi","year":"2011","journal-title":"J. Appl. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1152\/jappl.1998.84.3.830","article-title":"Depressed ventilatory response to hypoxia in hypothermic newborn piglets: Role of glutamate","volume":"84","author":"McCormick","year":"1998","journal-title":"J. Appl. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0034-5687(99)00072-9","article-title":"Brainstem amino acid neurotransmitters and hypoxic ventilatory response","volume":"118","author":"Hoop","year":"1999","journal-title":"Respir. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.brainres.2006.08.083","article-title":"Brain distribution of cytokine mRNA induced by systemic administration of interleukin-1\u03b2 or tumor necrosis factor \u03b1","volume":"1120","author":"Churchill","year":"2006","journal-title":"Brain Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.resp.2011.05.008","article-title":"Airway inflammation and central respiratory control: Results from In Vivo and In Vitro neonatal rat","volume":"178","author":"Gresham","year":"2011","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1152\/japplphysiol.00542.2014","article-title":"Il-1\u03b2 and prostaglandin E2 attenuate the hypercapnic as well as the hypoxic respiratory response via prostaglandin E receptor type 3 in neonatal mice","volume":"117","author":"Siljehav","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1080\/21645515.2015.1034921","article-title":"Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications","volume":"11","author":"Matin","year":"2015","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6578","DOI":"10.1523\/JNEUROSCI.20-17-06578.2000","article-title":"Lipopolysaccharide activates specific populations of hypothalamic and brainstem neurons that project to the spinal cord","volume":"20","author":"Zhang","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1124\/pr.56.3.3","article-title":"Cyclooxygenase isozymes: The biology of prostaglandin synthesis and inhibition","volume":"56","author":"Simmons","year":"2004","journal-title":"Pharmacol. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/med.21306","article-title":"Inhibitors of microsomal prostaglandin E2 synthase-1 enzyme as emerging anti-inflammatory candidates","volume":"34","author":"Silakari","year":"2014","journal-title":"Med. Res. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1177\/0883073809338066","article-title":"Fetal inflammatory response and brain injury in the preterm newborn","volume":"24","author":"Malaeb","year":"2009","journal-title":"J. Child Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1097\/CCM.0b013e3181cb1158","article-title":"Cyclooxygenase-2 inhibition provides lasting protection against neonatal hypoxic-ischemic brain injury","volume":"38","author":"Fathali","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S1473-3099(14)70710-8","article-title":"Infection-induced inflammation and cerebral injury in preterm infants","volume":"14","author":"Strunk","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12974-015-0397-2","article-title":"New means to assess neonatal inflammatory brain injury","volume":"12","author":"Jin","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nn778","article-title":"PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons","volume":"5","author":"Ahmadi","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1152\/jn.00696.2004","article-title":"Endogenous PGE2 regulates membrane excitability and synaptic transmission in hippocampal CA1 pyramidal neurons","volume":"93","author":"Chen","year":"2005","journal-title":"J. Neurophysiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.neuroscience.2007.01.053","article-title":"Prostaglandin E2 depresses solitary tract- mediated synaptic transmission in the nucleus tractus solitarius","volume":"146","author":"Laaris","year":"2007","journal-title":"Neuroscience"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1111\/j.1460-9568.2008.06296.x","article-title":"Dual modulation of synaptic transmission in the nucleus tractus solitarius by prostaglandin E2 synthesized downstream of IL-1\u03b2","volume":"27","author":"Marty","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1124\/jpet.114.217372","article-title":"Cyclooxygenase 2 inhibitor celecoxib inhibits glutamate release by attenuating the PGE2\/EP2 pathway in rat cerebral cortex endings","volume":"351","author":"Lin","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9894","DOI":"10.1073\/pnas.0611468104","article-title":"The induced prostaglandin E2 pathway is a key regulator of the respiratory response to infection and hypoxia in neonates","volume":"104","author":"Hofstetter","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e14170","DOI":"10.7554\/eLife.14170","article-title":"CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture","volume":"5","author":"Forsberg","year":"2016","journal-title":"eLife"},{"key":"ref_89","first-page":"687","article-title":"Inhibition of breathing movements in fetal sheep by prostaglandins","volume":"54","author":"Kitterman","year":"1983","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1152\/jappl.1988.64.5.2160","article-title":"Prostaglandin E2 causes hypoventilation and apnea in newborn lambs","volume":"64","author":"Guerra","year":"1988","journal-title":"J. Appl. Physiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1113\/jphysiol.2014.279794","article-title":"Prostaglandin E2 differentially modulates the central control of eupnoea, sighs and gasping in mice","volume":"593","author":"Koch","year":"2015","journal-title":"J. Physiol."},{"key":"ref_92","first-page":"360","article-title":"Indomethacin-induced fetal breathing: Mechanism and site of action","volume":"57","author":"Jansen","year":"1984","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nm1362","article-title":"Prostaglandin E2 EP1 receptors: Downstream effectors of COX-2 neurotoxicity","volume":"12","author":"Kawano","year":"2006","journal-title":"Nat. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1038\/jcbfm.2013.69","article-title":"Prostaglandin E2 type 1 receptors contribute to neuronal apoptosis after transient forebrain ischemia","volume":"33","author":"Shimamura","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.neulet.2011.09.005","article-title":"Function of prostaglandin E2EP receptors in the acute outcome of rodent hypoxic ischemic encephalopathy","volume":"504","author":"Taniguchi","year":"2011","journal-title":"Neurosci. Lett."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tins.2005.06.005","article-title":"The many faces of CREB","volume":"28","author":"Carlezon","year":"2005","journal-title":"Trends Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4049\/jimmunol.1101029","article-title":"Regulation of immune responses by prostaglandin E2","volume":"188","author":"Kalinski","year":"2011","journal-title":"J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4362","DOI":"10.1172\/JCI46279","article-title":"Signaling via the prostaglandin E2 receptor EP4 exerts neuronal and vascular protection in a mouse model of cerebral ischemia","volume":"121","author":"Liang","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1471-4159.2010.07080.x","article-title":"Creb: A multifaceted regulator of neuronal plasticity and protection","volume":"116","author":"Sakamoto","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1523\/JNEUROSCI.4485-03.2004","article-title":"Neuroprotective function of the PGE2 EP2 receptor in cerebral ischemia","volume":"24","author":"McCullough","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.neulet.2008.04.054","article-title":"Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia","volume":"438","author":"Li","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/glia.20220","article-title":"Microglial EP2 is critical to neurotoxicity from activated cerebral innate immunity","volume":"52","author":"Shie","year":"2005","journal-title":"Glia"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/(SICI)1096-9861(20000612)421:4<543::AID-CNE6>3.0.CO;2-3","article-title":"Immunohistochemical localization of prostaglandin EP3 receptor in the rat nervous system","volume":"421","author":"Nakamura","year":"2000","journal-title":"J. Comp. Neurol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s12035-009-8066-z","article-title":"Neuroinflammation and memory: The role of prostaglandins","volume":"40","author":"Hein","year":"2009","journal-title":"Mol. Neurobiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1111\/ejn.12909","article-title":"Genetic deletion of the prostaglandin E2 E prostanoid receptor subtype 3 improves anatomical and functional outcomes after intracerebral hemorrhage","volume":"41","author":"Leclerc","year":"2015","journal-title":"Eur J. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.biocel.2003.08.006","article-title":"Prostanoids and prostanoid receptors in signal transduction","volume":"36","author":"Leclerc","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fneur.2012.00145","article-title":"Putative role of prostaglandin receptor in intracerebral hemorrhage","volume":"3","author":"Mohan","year":"2012","journal-title":"Front. Neurol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.expneurol.2014.02.012","article-title":"Protection by vascular prostaglandin E2 signaling in hypoxic ischemic encephalopathy","volume":"255","author":"Taniguchi","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.prostaglandins.2009.04.003","article-title":"Emerging roles of PGE2 receptors in models of neurological disease","volume":"91","author":"Andreasson","year":"2010","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.4049\/jimmunol.0903487","article-title":"The prostaglandin E2 EP4 receptor exerts anti-inflammatory effects in brain innate immunity","volume":"184","author":"Shi","year":"2010","journal-title":"J. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1046\/j.1460-9568.1999.00682.x","article-title":"Distribution, regulation and colocalization of the genes encoding the EP2- and EP4-PGE2 receptors in the rat brain and neuronal responses to systemic inflammation","volume":"11","author":"Zhang","year":"1999","journal-title":"Eur. J. Neurosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0301-2115(00)00247-5","article-title":"Effects of intrauterine IL-6 and IL-8 on the expression of surfactant apoprotein mRNAs in the fetal rat lung","volume":"93","author":"Ikegami","year":"2000","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_113","first-page":"L999","article-title":"Lipopolysaccharide increases alveolar type II cell number in fetal mouse lungs through Toll-like receptor 4 and NF-\u03baB","volume":"287","author":"Prince","year":"2004","journal-title":"Am. J. Physiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1172\/JCI119494","article-title":"Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal rabbits and improves lung stability after premature birth","volume":"99","author":"Bry","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1203\/00006450-200012000-00014","article-title":"Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs","volume":"48","author":"Willet","year":"2000","journal-title":"Pediatr. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1164\/ajrccm.165.6.2108053","article-title":"Early gestational intra-amniotic endotoxin: Lung function, surfactant, and morphometry","volume":"165","author":"Moss","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1164\/rccm.2203030","article-title":"Increased IP-10 and MIG expression after intramniotic endotoxin in preterm lamb lung","volume":"167","author":"Kallapur","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_118","first-page":"L1178","article-title":"Vascular changes after intraamniotic endotoxin in preterm lamb lungs","volume":"287","author":"Kallapur","year":"2004","journal-title":"Am. J. Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5061","DOI":"10.1113\/jphysiol.2013.259119","article-title":"Intrauterine inflammation alters fetal cardiopulmonary and cerebral hemodynamics in sheep","volume":"591","author":"Galinsky","year":"2013","journal-title":"J. Physiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/sj.jp.7211240","article-title":"Histologic chorioamnionitis: An occult marker of severe pulmonary hypertension in the term newborn","volume":"25","author":"Woldesenbet","year":"2005","journal-title":"J. Perinatol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000101343","article-title":"Recent advances in the pathogenesis and treatment of persistent pulmonary hypertension of the newborn","volume":"91","author":"Abman","year":"2007","journal-title":"Neonatology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1097\/PCC.0b013e3181c76cdc","article-title":"Neonatal pulmonary hypertension","volume":"11","author":"Steinhorn","year":"2010","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1152\/japplphysiol.01336.2009","article-title":"Intrauterine inflammation causes pulmonary hypertension and cardiovascular sequelae in preterm lambs","volume":"108","author":"Polglase","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1152\/japplphysiol.00995.2011","article-title":"Inflammation in utero exacerbates ventilation-induced brain injury in preterm lambs","volume":"112","author":"Polglase","year":"2012","journal-title":"J. Appl. Physiol."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/10\/917\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:15:16Z","timestamp":1760166916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/10\/917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,15]]},"references-count":124,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["children8100917"],"URL":"https:\/\/doi.org\/10.3390\/children8100917","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,15]]}}}