{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:49:51Z","timestamp":1780105791094,"version":"3.54.0"},"reference-count":57,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["PED"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>Encephalopathy of prematurity (EP) is common in preterm, low birth weight infants who require postnatal mechanical ventilation. The worst types of EP are the hemorrhagic forms, including choroid plexus, germinal matrix, periventricular, and intraventricular hemorrhages. Survivors exhibit life-long cognitive, behavioral, and motor abnormalities. Available preclinical models do not fully recapitulate the salient features of hemorrhagic EP encountered in humans. In this study, the authors evaluated a novel model using rats that featured tandem insults of transient prenatal intrauterine ischemia (IUI) plus transient postnatal raised intrathoracic pressure (RIP).<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Timed-pregnant Wistar rats were anesthetized and underwent laparotomy on embryonic Day 19. Intrauterine ischemia was induced by clamping the uterine and ovarian vasculature for 20 minutes. Natural birth occurred on embryonic Day 22. Six hours after birth, the pups were subjected to an episode of RIP, induced by injecting glycerol (50%, 13 \u03bcl\/g intraperitoneally). Control groups included naive, sham surgery, and IUI alone. Pathological, histological, and behavioral analyses were performed on pups up to postnatal Day 52.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Compared with controls, pups subjected to IUI+RIP exhibited significant increases in postnatal mortality and hemorrhages in the choroid plexus, germinal matrix, and periventricular tissues as well as intraventricularly. On postnatal Days 35\u201352, they exhibited significant abnormalities involving complex vestibulomotor function and rapid spatial learning. On postnatal Day 52, the brain and body mass were significantly reduced.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Tandem insults of IUI plus postnatal RIP recapitulate many features of the hemorrhagic forms of EP found in humans, suggesting that these insults in combination may play important roles in pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2011.9.peds11174","type":"journal-article","created":{"date-parts":[[2011,12,2]],"date-time":"2011-12-02T23:18:22Z","timestamp":1322867902000},"page":"628-639","source":"Crossref","is-referenced-by-count":6,"title":["Tandem insults of prenatal ischemia plus postnatal raised intrathoracic pressure in a novel rat model of encephalopathy of prematurity"],"prefix":"10.3171","volume":"8","author":[{"given":"Michael T.","family":"Koltz","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cigdem","family":"Tosun","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Kurland","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turhan","family":"Coksaygan","sequence":"additional","affiliation":[{"name":"Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph J.","family":"Castellani","sequence":"additional","affiliation":[{"name":"Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr","family":"Gerzanich","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Marc","family":"Simard","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"},{"name":"Pathology, and"},{"name":"Physiology, University of Maryland School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-0080628","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1542\/peds.2008-2816","article-title":"Meta-analysis of neurobehavioral outcomes in very preterm and\/or very low birth weight children","volume":"124","author":"Aarnoudse-Moens","year":"2009"},{"key":"b2-0080628","series-title":"Hypertension","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1161\/01.HYP.0000053448.95913.3D","article-title":"Placental insufficiency leads to development of hypertension in growth-restricted offspring","volume":"41","author":"Alexander","year":"2003"},{"key":"b3-0080628","series-title":"Pediatr Neurol","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/S0887-8994(03)00404-1","article-title":"Subependymal veins in premature neonates: implications for hemorrhage","volume":"30","author":"Anstrom","year":"2004"},{"key":"b4-0080628","series-title":"Am J Dis Child","first-page":"617","article-title":"Neuropathologic findings in short-term survivors of intraventricular hemorrhage","volume":"141","author":"Armstrong","year":"1987"},{"key":"b5-0080628","series-title":"J Neurosci","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1523\/JNEUROSCI.22-02-00455.2002","article-title":"Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia","volume":"22","author":"Back","year":"2002"},{"key":"b6-0080628","series-title":"J Child Neurol","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1177\/08830738060210050201","article-title":"Animal models of germinal matrix hemorrhage","volume":"21","author":"Balasubramaniam","year":"2006"},{"key":"b7-0080628","series-title":"Pediatr Res","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1203\/PDR.0b013e3181c1b176","article-title":"Intraventricular hemorrhage in premature infants: mechanism of disease","volume":"67","author":"Ballabh","year":"2010"},{"key":"b8-0080628","series-title":"Nat Med","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/nm1558","article-title":"Angiogenic inhibition reduces germinal matrix hemorrhage","volume":"13","author":"Ballabh","year":"2007"},{"key":"b9-0080628","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1542\/peds.2007-0211","article-title":"Neurodevelopmental outcome in survivors of periventricular hemorrhagic infarction","volume":"120","author":"Bassan","year":"2007"},{"key":"b10-0080628","series-title":"Pediatr Res","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1203\/00006450-199507000-00019","article-title":"Intrauterine hypoxiaischemia increases N-methyl-D-aspartate-induced cGMP formation and glutamate accumulation in cultured rat cerebellar granule cells","volume":"38","author":"Cai","year":"1995"},{"key":"b11-0080628","series-title":"Arch Dis Child Fetal Neonatal Ed","doi-asserted-by":"publisher","first-page":"F169","DOI":"10.1136\/adc.2009.174433","article-title":"Two-year neurodevelopmental outcome of preterm born children \u2264 750 g at birth","volume":"96","author":"Claas","year":"2011"},{"key":"b12-0080628","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"204","DOI":"10.3171\/jns.1983.58.2.0204","article-title":"The role of intracranial hypotension in neonatal intraventricular hemorrhage","volume":"58","author":"Conner","year":"1983"},{"key":"b13-0080628","series-title":"Am Stat","first-page":"124","article-title":"Rank transformations as a bridge between parametric and nonparametric statistics","volume":"35","author":"Conover","year":"1981"},{"key":"b14-0080628","series-title":"The Anatomy of the Laboratory Mouse","first-page":"125","author":"Cook","year":"1965"},{"key":"b15-0080628","series-title":"Brain Res Brain Res Rev","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/S0165-0173(01)00067-4","article-title":"Applications of the Morris water maze in the study of learning and memory","volume":"36","author":"D'Hooge","year":"2001"},{"key":"b16-0080628","series-title":"Behav Neurosci","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1037\/0735-7044.113.5.914","article-title":"The hippocampus is not necessary for a place response but may be necessary for pliancy","volume":"113","author":"Day","year":"1999"},{"key":"b17-0080628","series-title":"Neurosci Res","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/S0168-0102(98)00096-0","article-title":"Neonatal reversible focal cerebral ischemia: a new model","volume":"32","author":"Derugin","year":"1998"},{"key":"b18-0080628","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1542\/peds.2010-0710","article-title":"Adult outcome of extremely preterm infants","volume":"126","author":"Doyle","year":"2010"},{"key":"b19-0080628","series-title":"Neurosci Behav Physiol","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s11055-009-9235-2","article-title":"Ontogenetic characteristics of behavior in rats subjected to hypoxia on day 14 or day 18 of embryogenesis","volume":"40","author":"Dubrovskaya","year":"2010"},{"key":"b20-0080628","series-title":"J Child Neurol","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1177\/08830738050200120301","article-title":"Neuropathologic substrate of cerebral palsy","volume":"20","author":"Folkerth","year":"2005"},{"key":"b21-0080628","series-title":"Cereb Cortex","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/cercor\/12.2.199","article-title":"Vascularization in the primate visual cortex during development","volume":"12","author":"Fonta","year":"2002"},{"key":"b22-0080628","series-title":"Stroke","doi-asserted-by":"publisher","first-page":"3378","DOI":"10.1161\/STROKEAHA.107.510883","article-title":"Characterization of acute brain injuries and neurobehavioral profiles in a rabbit model of germinal matrix hemorrhage","volume":"39","author":"Georgiadis","year":"2008"},{"key":"b23-0080628","series-title":"Circ Res","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1161\/01.RES.0000097872.69043.A0","article-title":"Alternative splicing of cGMP-dependent protein kinase I in angiotensin-hypertension: novel mechanism for nitrate tolerance in vascular smooth muscle","volume":"93","author":"Gerzanich","year":"2003"},{"key":"b24-0080628","series-title":"AJNR Am J Neuroradiol","first-page":"219","article-title":"Human germinal matrix: venous origin of hemorrhage and vascular characteristics","volume":"18","author":"Ghazi-Birry","year":"1997"},{"key":"b25-0080628","series-title":"Aust Paediatr J","first-page":"343","article-title":"Intrathoracic pressure fluctuations and periventricular haemorrhage in the newborn","volume":"23","author":"Hillman","year":"1987"},{"key":"b26-0080628","series-title":"Am J Perinatol","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1055\/s-0029-1214234","article-title":"Clinical patterns in extremely preterm (22 to 24 weeks of gestation) infants in relation to survival time and prognosis","volume":"26","author":"Iijima","year":"2009"},{"key":"b27-0080628","series-title":"Childs Nerv Syst","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1007\/s00381-006-0050-6","article-title":"The incidence, timing, and predisposing factors of germinal matrix and intraventricular hemorrhage (GMH\/IVH) in preterm neonates","volume":"22","author":"Kadri","year":"2006"},{"key":"b28-0080628","series-title":"Arch Dis Child Fetal Neonatal Ed","first-page":"F153","article-title":"Pathogenesis of cerebral white matter injury of prematurity","volume":"93","author":"Khwaja","year":"2008"},{"key":"b29-0080628","series-title":"Semin Pediatr Neurol","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.spen.2009.09.003","article-title":"The encephalopathy of prematurity: one pediatric neuropathologist's perspective","volume":"16","author":"Kinney","year":"2009"},{"key":"b30-0080628","series-title":"Arch Dis Child Fetal Neonatal Ed","doi-asserted-by":"publisher","first-page":"F188","DOI":"10.1136\/fn.82.3.F188","article-title":"Low superior vena cava flow and intraventricular haemorrhage in preterm infants","volume":"82","author":"Kluckow","year":"2000"},{"key":"b31-0080628","series-title":"Neuron","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.neuron.2004.05.010","article-title":"A double dissociation between hippocampal subfields: differential time course of CA3 and CA1 place cells for processing changed environments","volume":"42","author":"Lee","year":"2004"},{"key":"b32-0080628","series-title":"Science","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1126\/science.1135801","article-title":"Pattern separation in the dentate gyrus and CA3 of the hippocampus","volume":"315","author":"Leutgeb","year":"2007"},{"key":"b33-0080628","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1097\/00006123-199711000-00015","article-title":"Outcome for preterm infants with germinal matrix hemorrhage and progressive hydrocephalus","volume":"41","author":"Levy","year":"1997"},{"key":"b34-0080628","series-title":"Science","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1126\/science.1140263","article-title":"Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network","volume":"317","author":"McHugh","year":"2007"},{"key":"b35-0080628","series-title":"Pediatr Neurol","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.pediatrneurol.2003.10.001","article-title":"Selective vulnerability in the developing central nervous system","volume":"30","author":"McQuillen","year":"2004"},{"key":"b36-0080628","series-title":"J Neurosci Methods","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/0165-0270(84)90007-4","article-title":"Developments of a water-maze procedure for studying spatial learning in the rat","volume":"11","author":"Morris","year":"1984"},{"key":"b37-0080628","series-title":"Hum Pathol","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/0046-8177(90)90256-5","article-title":"Germinal matrix hemorrhage of venous origin in preterm neonates","volume":"21","author":"Nakamura","year":"1990"},{"key":"b38-0080628","series-title":"Science","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1126\/science.1151120","article-title":"Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning","volume":"319","author":"Nakashiba","year":"2008"},{"key":"b39-0080628","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/0006-8993(93)91226-I","article-title":"Early changes of macrophage-like immunoreactivity in the rat inferior olive after intraperitoneal 3-acetylpyridine injection","volume":"610","author":"Ogawa","year":"1993"},{"key":"b40-0080628","series-title":"J Neuropathol Exp Neurol","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1097\/NEN.0b013e3181fbf6d6","article-title":"Glibenclamide reduces hippocampal injury and preserves rapid spatial learning in a model of traumatic brain injury","volume":"69","author":"Patel","year":"2010"},{"key":"b41-0080628","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1097\/00006123-199705000-00021","article-title":"Outcome, cost analysis, and long-term follow-up in preterm infants with massive grade IV germinal matrix hemorrhage and progressive hydrocephalus","volume":"40","author":"Pikus","year":"1997"},{"key":"b42-0080628","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1038\/jcbfm.2009.56","article-title":"Rodent neonatal bilateral carotid artery occlusion with hypoxia mimics human hypoxic-ischemic injury","volume":"29","author":"Recker","year":"2009"},{"key":"b43-0080628","series-title":"AJNR Am J Neuroradiol","first-page":"619","article-title":"Choroid plexus hemorrhage in premature neonates: recognition by sonography","volume":"3","author":"Reeder","year":"1982"},{"key":"b44-0080628","series-title":"Ann Neurol","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"Rice","year":"1981"},{"key":"b45-0080628","series-title":"J Comp Neurol","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/cne.1324","article-title":"Postnatal development of catecholamine inputs to the paraventricular nucleus of the hypothalamus in rats","volume":"438","author":"Rinaman","year":"2001"},{"key":"b46-0080628","series-title":"Neurobiol Dis","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.nbd.2004.10.024","article-title":"Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats","volume":"18","author":"Robinson","year":"2005"},{"key":"b47-0080628","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"e46","DOI":"10.1542\/peds.2007-3305","article-title":"Risk factors for adverse outcome in preterm infants with periventricular hemorrhagic infarction","volume":"122","author":"Roze","year":"2008"},{"key":"b48-0080628","series-title":"Biol Neonate","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1159\/000244327","article-title":"A rat model for hypoxicischemic brain damage in very premature infants","volume":"69","author":"Sheldon","year":"1996"},{"key":"b49-0080628","series-title":"J Neural Transm","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1007\/s007020070004","article-title":"The effects of physostigmine and cholinergic receptor ligands on novelty-induced neophobia","volume":"107","author":"Sienkiewicz-Jarosz","year":"2000"},{"key":"b50-0080628","series-title":"Pediatr Res","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1203\/PDR.0b013e318186e5a9","article-title":"Sulfonylurea receptor 1 in the germinal matrix of premature infants","volume":"64","author":"Simard","year":"2008"},{"key":"b51-0080628","series-title":"Biol Neonate","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1159\/000047125","article-title":"Prenatal influence of ischemia-hypoxia-induced intrauterine growth retardation on brain development and behavioral activity in rats","volume":"80","author":"Tashima","year":"2001"},{"key":"b52-0080628","series-title":"Obstet Gynecol","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1097\/01.AOG.0000130838.02410.b7","article-title":"Intraventricular hemorrhage and periventricular leukomalacia in preterm infants","volume":"104","author":"Vergani","year":"2004"},{"key":"b53-0080628","series-title":"Lancet Neurol","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/S1474-4422(08)70294-1","article-title":"Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances","volume":"8","author":"Volpe","year":"2009"},{"key":"b54-0080628","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1542\/peds.2005-0191","article-title":"Encephalopathy of prematurity includes neuronal abnormalities","volume":"116","author":"Volpe","year":"2005"},{"key":"b55-0080628","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1089\/neu.2007.0274","article-title":"Deficits in novelty exploration after controlled cortical impact","volume":"24","author":"Wagner","year":"2007"},{"key":"b56-0080628","series-title":"Prog Neurobiol","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.pneurobio.2010.08.001","article-title":"Preclinical and clinical research on inflammation after intracerebral hemorrhage","volume":"92","author":"Wang","year":"2010"},{"key":"b57-0080628","series-title":"Pediatrics","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1542\/peds.98.4.719","article-title":"Neonatal cranial ultrasound abnormalities in low birth weight infants: relation to cognitive outcomes at six years of age","volume":"98","author":"Whitaker","year":"1996"}],"container-title":["Journal of Neurosurgery: Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/8\/6\/article-p628.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/8\/6\/article-p628.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-pediatr\/8\/6\/article-p628.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T15:55:17Z","timestamp":1681574117000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-pediatr\/8\/6\/article-p628.xml"}},"subtitle":["Laboratory investigation"],"short-title":[],"issued":{"date-parts":[[2011,12]]},"references-count":57,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/2011.9.peds11174","relation":{},"ISSN":["1933-0707","1933-0715"],"issn-type":[{"value":"1933-0707","type":"print"},{"value":"1933-0715","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12]]}}}