{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:23Z","timestamp":1787027723222,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["2R15D077544"],"award-info":[{"award-number":["2R15D077544"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Hypoxic-Ischemic (HI) brain injury in the neonate contributes to life-long cognitive impairment. Early diagnosis and therapeutic interventions are critical but limited. We previously reported in a rat model of HI two interventional approaches that improve cognitive and sensory function: administration of Inter-alpha Inhibitor Proteins (IAIPs) and early experience in an eight-arm radial water maze (RWM) task. Here, we expanded these studies to examine the combined effects of IAIPs and multiple weeks of RWM assessment beginning with juvenile or adolescent rats to evaluate optimal age windows for behavioral interventions. Subjects were divided into treatment groups; HI with vehicle, sham surgery with vehicle, and HI with IAIPs, and received either juvenile (P31 initiation) or adolescent (P52 initiation) RWM testing, followed by adult retesting. Error rates on the RWM decreased across weeks for all conditions. Whereas, HI injury impaired global performance as compared to shams. IAIP-treated HI subjects tested as juveniles made fewer errors as compared to their untreated HI counterparts. The juvenile group made significantly fewer errors on moderate demand trials and showed improved retention as compared to the adolescent group during the first week of adult retesting. Together, results support and extend our previous findings that combining behavioral and anti-inflammatory interventions in the presence of HI improves subsequent learning performance. Results further indicate sensitive periods for behavioral interventions to improve cognitive outcomes. Specifically, early life cognitive experience can improve long-term learning performance even in the presence of HI injury. Results from this study provide insight into typical brain development and the impact of developmentally targeted therapeutics and task-specific experience on subsequent cognitive processing.<\/jats:p>","DOI":"10.3390\/brainsci10120999","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:42:47Z","timestamp":1608201767000},"page":"999","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of Juvenile or Adolescent Working Memory Experience and Inter-Alpha Inhibitor Protein Treatment after Neonatal Hypoxia-Ischemia"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-0171","authenticated-orcid":false,"given":"Aaron","family":"Bradford","sequence":"first","affiliation":[{"name":"Neuroscience Program, School of Health Sciences, Regis College, 235 Wellesley Street, Weston, MA 02493, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Neuroscience Program, School of Health Sciences, Regis College, 235 Wellesley Street, Weston, MA 02493, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Kearney","sequence":"additional","affiliation":[{"name":"Neuroscience Program, School of Health Sciences, Regis College, 235 Wellesley Street, Weston, MA 02493, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Theriault","sequence":"additional","affiliation":[{"name":"Neuroscience Program, School of Health Sciences, Regis College, 235 Wellesley Street, Weston, MA 02493, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2697-7963","authenticated-orcid":false,"given":"Yow-Pin","family":"Lim","sequence":"additional","affiliation":[{"name":"ProThera Biologics, Inc., 349 Eddy Street, Providence, RI 02903, USA"},{"name":"Department of Pathology and Laboratory Medicine, The Alpert Medical School of Brown University, 222 Richmond Street, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6532-7683","authenticated-orcid":false,"given":"Barbara S.","family":"Stonestreet","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Alpert Medical School of Brown University, Women &amp; Infants Hospital of Rhode Island, 101 Dudley Street, Providence, RI 02905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Threlkeld","sequence":"additional","affiliation":[{"name":"Neuroscience Program, School of Health Sciences, Regis College, 235 Wellesley Street, Weston, MA 02493, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1148\/rg.282075066","article-title":"Hypoxic-ischemic brain injury: Imaging findings from birth to adulthood","volume":"28","author":"Huang","year":"2008","journal-title":"Radiographics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"316","DOI":"10.4103\/0971-3026.190421","article-title":"Magnetic resonance imaging spectrum of perinatal hypoxic-ischemic brain injury","volume":"26","author":"Varghese","year":"2016","journal-title":"Ind. J. Radiol. Imaging"},{"key":"ref_3","doi-asserted-by":"crossref","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","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fped.2016.00114","article-title":"Pre-term hypoxic-ischemic encephalopathy","volume":"4","author":"Gopagondanahalli","year":"2016","journal-title":"Front. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.bbr.2013.10.038","article-title":"Behavioral and histological outcomes following neonatal HI injury in a preterm (P3) and term (P7) rodent model","volume":"259","author":"Alexander","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fncel.2017.00078","article-title":"Neonatal hypoxia ischaemia: Mechanisms, models, and therapeutic challenges","volume":"11","author":"Millar","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/ana.23647","article-title":"Neonatal encephalopathy: An inadequate term for hypoxic-ischemic encephalopathy","volume":"72","author":"Volpe","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1056\/NEJMoa1112066","article-title":"Childhood outcomes after hypothermia for neonatal encephalopathy","volume":"366","author":"Shankaran","year":"2012","journal-title":"NEJM"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e624","DOI":"10.1542\/peds.2014-1566","article-title":"Cognitive outcomes after neonatal encephalopathy","volume":"135","author":"Pappas","year":"2015","journal-title":"Pediatrics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fneur.2015.00198","article-title":"Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy\u2014Where to from here?","volume":"6","author":"Davidson","year":"2015","journal-title":"Front. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"j3448","DOI":"10.1136\/bmj.j3448","article-title":"Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks\u2019 gestation in France in 2011: EPIPAGE-2 cohort study","volume":"358","author":"Pierrat","year":"2017","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shah, P.S., Ohlsson, A., and Perlman, M. (2007). Hypothermia to Treat Neonatal Hypoxic Ischemic Encephalopathy. Arch. Ped. Adolesc. Med., 161.","DOI":"10.1001\/archpedi.161.10.951"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/pr.2011.8","article-title":"The effect of whole-body cooling on brain metabolism following perinatal hypoxic-ischemic injury","volume":"71","author":"Corbo","year":"2012","journal-title":"Pediatric Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/ana.23843","article-title":"Elevated temperature and 6- to 7-year outcome of neonatal encephalopathy","volume":"73","author":"Laptook","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1055\/s-0038-1676973","article-title":"Neurodevelopmental outcomes in neonates with mild hypoxic ischemic encephalopathy treated with therapeutic hypothermia","volume":"36","author":"Rao","year":"2019","journal-title":"Am. J. Perinatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/jdn.10022","article-title":"Benefits of hypothermia in neonatal arterial ischemic strokes: A preclinical study","volume":"80","author":"Chevin","year":"2020","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.brainres.2011.06.001","article-title":"Ibuprofin inhibits neuroinflammation and attenuates white matter damage following hypoxia-ischemia in the immature rodent brain","volume":"1402","author":"Carty","year":"2011","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.neuroscience.2011.03.033","article-title":"Efficacy of post-insult minocycline administration to alter long-term hypoxia-ischemia-induced damage to the serotinergic system in the immature rat brain","volume":"182","author":"Wixey","year":"2011","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Poupon-Bejuit, L., Rocha-Ferriera, E., Thornton, C., Hagberg, H., and Rahim, A.A. (2020). Neuroprotective effects of diabetes drugs for the treatment of neonatal hypoxia-ischemia encephalopathy. Front. Cell Neurosci., 14.","DOI":"10.3389\/fncel.2020.00112"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/03008200802325458","article-title":"Structure and function of inter-alpha-trypsin inhibitor heavy chains","volume":"49","author":"Zhuo","year":"2008","journal-title":"Connect. Tissue Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.jpeds.2010.04.075","article-title":"Inter-alpha inhibitor protein level in neonates predicts necrotizing enterocolitis","volume":"157","author":"Chaaban","year":"2010","journal-title":"J. Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.neuroscience.2016.03.009","article-title":"Expression and localization of inter-alpha inhibitors in the rodent brain","volume":"324","author":"Chen","year":"2016","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1177\/1535370213519195","article-title":"Ontogeny of inter-alpha inhibitor proteins in ovine brain and somatic tissues","volume":"239","author":"Spasova","year":"2014","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/jnr.24565","article-title":"Ontogeny of inter-alpha inhibitor protein (IAIP) expression in human brain","volume":"98","author":"Kim","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lord, M.S., Melrose, J., Day, A.J., and Whitelock, J.M. (2020). The inter-\u03b1-trypsin inhibitor family: Versatile molecules in biology and pathology. J. Histochem. Cytochem., 1\u201321.","DOI":"10.1369\/0022155420940067"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5101","DOI":"10.1128\/IAI.73.8.5101-5105.2005","article-title":"Inter-alpha inhibitor proteins are endogenous furin inhibitors and provide protection against experimental anthrax intoxication","volume":"73","author":"Opal","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.4049\/jimmunol.179.6.4187","article-title":"Inter-alpla-trypsin inhibitor attenuates complement activation and complement-induced lung injury","volume":"179","author":"Garandziotis","year":"2007","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1203\/PDR.0b013e3181e9fdf0","article-title":"Inter-alpha inhibitor protein administration improves survival from neonatal sepsis in mice","volume":"68","author":"Singh","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_29","doi-asserted-by":"crossref","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","journal-title":"Ann. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Winerdal, M., Winerdal, M.E., Kinn, J., Urmaliya, V., Winqvist, O., and \u00c2d\u00e9n, U. (2012). Long lasting local and systemic inflammation after cerebral hypoxic ischemia in newborn mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036422"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.neulet.2004.07.065","article-title":"Magnetic resonance imaging of differential gray versus white matter injury following a mild or moderate hypoxic-ischemic insult in neonatal rats","volume":"368","author":"Qiao","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3389\/fped.2020.00289","article-title":"Neonatal hypoxic-ischemic encephalopathy yields permanent deficits in learning acquisition: A preclinical touchscreen assessment","volume":"8","author":"Maxwell","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ijdevneu.2017.10.008","article-title":"Alterations in inter-alpha inhibitor protein expression after hypoxic-ischemic brain injury in neonatal rats","volume":"65","author":"Disdier","year":"2018","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1093\/jnen\/nlz051","article-title":"Inter-alpha inhibitor proteins modulate neuroinflammatory biomarkers after hypoxia-ischemia in neonatal rats","volume":"78","author":"Chen","year":"2019","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.expneurol.2019.03.013","article-title":"Neuroprotective effects of inter-alpha inhibitor proteins after hypoxic-ischemic brain injury in neonatal rats","volume":"317","author":"Chen","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.expneurol.2014.07.012","article-title":"Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes","volume":"261","author":"Threlkeld","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bbr.2016.01.016","article-title":"Effects of age, experience and inter-alpha inhibitor proteins on working memory and neuronal plasticity after neonatal hypoxia-ischemia","volume":"302","author":"Gaudet","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bbi.2017.03.004","article-title":"Immuno-modulator inter-alpha inhibitor proteins ameliorate complex auditory processing deficits in rats with neonatal hypoxic-ischemic brain injury","volume":"64","author":"Threlkeld","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_39","first-page":"e50940","article-title":"Use of an eight-arm radial water maze to assess working and reference memory following neonatal brain injury","volume":"82","author":"Penley","year":"2013","journal-title":"JoVE"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"113087","DOI":"10.1016\/j.expneurol.2019.113087","article-title":"Neonatal cerebral hypoxia-ischemia in mice triggers age-dependent vascular effects and disabilities in adults; implication of tissue plasminogen activator (tPA)","volume":"323","author":"Arabo","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1093\/brain\/awh618","article-title":"Object working memory deficits predicted by early brain injury and development in the preterm infant","volume":"128","author":"Woodward","year":"2005","journal-title":"Brain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e639","DOI":"10.1542\/peds.2010-1421","article-title":"Executive and memory function in adolescents born very preterm","volume":"127","author":"Luu","year":"2011","journal-title":"Pediatrics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/pr.2013.206","article-title":"Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990","volume":"74","author":"Lee","year":"2013","journal-title":"Pediatr. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e20160659","DOI":"10.1542\/peds.2016-0659","article-title":"Early EEG grade and outcome at 6 years after mild neonatal hypoxic ischemic encephalopathy","volume":"138","author":"Murray","year":"2016","journal-title":"Pediatrics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/apa.14821","article-title":"Systematic review; long-term cognitive and behavioral outcomes of neonatal hypoxic-ischemic encephalopathy in children without cerebral palsy","volume":"109","author":"Schreglmann","year":"2020","journal-title":"Acta Pediatrica"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1053\/j.semperi.2016.05.011","article-title":"Changing definitions of long-term follow-up: Should \u201clong term\u201d be even longer?","volume":"40","author":"Hintz","year":"2016","journal-title":"Semin. Perinat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41390-018-0203-9","article-title":"Nurturing the preterm infant brain: Leveraging neuroplasticity to improve neurobehavioral outcomes","volume":"85","author":"DeMaster","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1542\/peds.113.4.846","article-title":"Early Experience Alters Brain Function and Structure","volume":"133","author":"Als","year":"2004","journal-title":"Pediatrics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.brainres.2008.04.010","article-title":"Early enriched housing results in partial recovery of memory deficits in female, but not in male, rats after neonatal hypoxia-ischemia","volume":"1218","author":"Pereira","year":"2008","journal-title":"Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.expneurol.2012.11.026","article-title":"Effects of daily environmental enrichment on behavior and dendritic spine density in hippocampus following neonatal hypoxia-ischemia in the rat","volume":"241","author":"Rojas","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/s41467-020-14762-7","article-title":"Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery","volume":"11","author":"Forbes","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/dmcn.13049","article-title":"Rethinking preventative post-discharge intervention programmes for very preterm infants and their parents","volume":"58","author":"Meijssen","year":"2016","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ijdevneu.2009.03.007","article-title":"Early acoustic discrimination experience ameliorates auditory processing deficits in male rats with cortical developmental disruption","volume":"27","author":"Threlkeld","year":"2009","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0166-4328(96)00167-2","article-title":"Comparison of effects of global cerebral ischaemia on spatial learning in the standard and radial water maze: Relationship of hippocampal damage to performance","volume":"85","author":"Nelson","year":"1997","journal-title":"Behav. Brain Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0197-4580(03)00041-1","article-title":"Effect of age on radial arm water maze-a test of spatial learning and memory","volume":"25","author":"McEwen","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bbr.2003.08.024","article-title":"Sex differences and correlations in a virtual Morris water task, a virtual radial arm maze, and mental rotation","volume":"151","author":"Astur","year":"2004","journal-title":"Behav. Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fnbeh.2014.00294","article-title":"Navigating to new frontiers in behavioral neuroscience: Traditional neuropsychological tests predict human performance on a rodent-inspired radial-arm maze","volume":"8","author":"Mennenga","year":"2014","journal-title":"Front. Behav. Neurosci."},{"key":"ref_58","first-page":"234","article-title":"Early testosterone modulated sex differences in behavioral outcome following neonatal hypoxia ischemia in rats","volume":"29","author":"Hill","year":"2011","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.expneurol.2014.01.003","article-title":"Sex differences in behavioral outcome following neonatal hypoxia ischemia: Insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury","volume":"254","author":"Smith","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.expneurol.2015.09.003","article-title":"Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI","volume":"275","author":"Waddell","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0031-9384(00)00259-6","article-title":"In two species, females exhibit superior working memory and inferior reference memory on the water radial arm maze","volume":"70","author":"Bimonte","year":"2000","journal-title":"Physiol. Behav."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0014-4886(03)00061-X","article-title":"Testosterone, but not nonaromatizable dihydrotestosterone, improves working memory and alters nerve growth factor levels in aged male rats","volume":"181","author":"Singleton","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0166-4328(02)00237-1","article-title":"Role of the neocortex in the water maze task in the rat: A detailed behavioral and Golgi-Cox analysis","volume":"138","author":"Hoh","year":"2003","journal-title":"Brain Behav. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0197-4580(94)00155-3","article-title":"Age-related spatial reference and working memory deficites assessed in the water maze","volume":"16","author":"Frick","year":"1995","journal-title":"Neurobiol. Aging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.neuroscience.2010.02.050","article-title":"Exercise and time-dependent benefits of learning and memory","volume":"167","author":"Berchtold","year":"2010","journal-title":"Neuroscience"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1159\/000362782","article-title":"Hypoxic\/ischemic and infectious events have cumulative effects on the risk of cerebral palsy in very-low-birth-weight preterm infants","volume":"106","author":"Wang","year":"2014","journal-title":"Neonatology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1001\/jama.292.19.2357","article-title":"Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection","volume":"292","author":"Stoll","year":"2004","journal-title":"JAMA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15761\/COGRM.1000281","article-title":"Relationship between hippocampal subfield volumes and memory function in adults born preterm with very low birth weight (VLBW)","volume":"6","author":"Aanes","year":"2020","journal-title":"Clin. Obstet. Gynecol. Reprod. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1542\/peds.2005-1368","article-title":"Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants","volume":"117","author":"Ehrenkranz","year":"2006","journal-title":"Pediatrics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1203\/00006450-199711000-00021","article-title":"Sensorimotor function and neuropathology five to six weeks after hypoxia-ischemia in seven-day-old rats","volume":"42","author":"Bona","year":"1997","journal-title":"Pediatr. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.bbr.2004.06.019","article-title":"Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic-ischemic injury","volume":"157","author":"Lubics","year":"2005","journal-title":"Behav. Brain Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.brainres.2011.12.024","article-title":"Effects of pre- and postnatal protein malnutrition in hypoxic-ischemic rats","volume":"1438","author":"Spindler","year":"2012","journal-title":"Brain Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1203\/00006450-200203000-00015","article-title":"Delayed postischemic hypothermia improves long-term behavioral outcome after cerebral hypoxia-ischemia in neonatal rats","volume":"51","author":"Wagner","year":"2002","journal-title":"Pediatr. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s12974-019-1595-0","article-title":"Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat","volume":"9","author":"Borjini","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.physbeh.2014.03.016","article-title":"Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder","volume":"130","author":"Patki","year":"2014","journal-title":"Physiol. Behav."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bbr.2018.06.033","article-title":"Effects of combined pre- and post-natal enrichment on anxiety-like, social, and cognitive behaviors in juvenile and adult rat offspring","volume":"353","author":"Sparling","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_77","first-page":"451","article-title":"Potentially obesogenic diets alter metabolic and neurobehavioural parameters in Wistar rats: A comparison between two dietary models","volume":"279","author":"Gouveia","year":"2020","journal-title":"J. Affect Disord."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrneurol.2015.13","article-title":"The role of inflammation in perinatal brain injury","volume":"11","author":"Hagberg","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12974-015-0251-6","article-title":"Sexually dimorphic outcomes and inflammatory responses in hypoxic-ischemic encephalopathy","volume":"12","author":"Mirza","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Villapol, S., Faivre, V., Joshi, P., Moretti, R., Besson, V.C., and Charriaut-Marlangue, C. (2019). Early sex differences in the immune-inflammatory responses to neonatal ischemic stroke. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153809"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1177\/0271678X19859465","article-title":"Inter-alpha inhibitor proteins attenuate lipopolysaccharide-induced blood-brain barrier disruption and downregulate circulating interleukin 6 in mice","volume":"40","author":"Logsdon","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/12\/999\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:46:16Z","timestamp":1760179576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/12\/999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,17]]},"references-count":81,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["brainsci10120999"],"URL":"https:\/\/doi.org\/10.3390\/brainsci10120999","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,17]]}}}