{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:12:03Z","timestamp":1790385123730,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,3,9]],"date-time":"2019-03-09T00:00:00Z","timestamp":1552089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"department of Pediatrics, NorthShore University HealthSystems"},{"name":"NIH","award":["R24NS104098-01A1"],"award-info":[{"award-number":["R24NS104098-01A1"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Apnea of prematurity is a common clinical condition that occurs in premature infants and results in intermittent hypoxia (IH) to brain and other organs. While short episodes of apnea are considered of no clinical significance, prolonged apnea with bradycardia and large oxygen desaturation is associated with adverse neurological and cognitive outcome. The mechanisms of cognitive deficits in IH are poorly understood. We hypothesized that brief but multiple episodes of severe oxygen desaturation accompanied by bradycardia may affect early and late synaptic plasticity and produce long\u2010term cognitive deficits.<\/jats:p><jats:p>C57BL\/6 mouse pups were exposed to IH paradigm consisting of alternating cycles of 5% oxygen for 2.5\u2009min and room air for 5\u201310\u2009min, 2\u2009h a day from P3 to P7. Long term potentiation (LTP) of synaptic strength in response to high frequency stimulation in hippocampal slices were examined 3 days and 6 weeks after IH. LTP was decreased in IH group relative to controls at both time points. That decrease was associated with deficits in spatial memory on Morris water maze and context fear conditioning test. Hypomyelination was observed in multiple gray and white matter areas on <jats:italic>in vivo<\/jats:italic> MRI using micromolecule proton fraction and ex vivo diffusion tensor imaging. No difference in caspase labeling was found between control and IH groups.<\/jats:p><jats:p>We conclude that early changes in synaptic plasticity occurring during severe episodes of neonatal IH and persisting to adulthood may represent functional and structural substrate for long term cognitive deficits.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2019.03.001","type":"journal-article","created":{"date-parts":[[2019,3,9]],"date-time":"2019-03-09T02:20:34Z","timestamp":1552098034000},"page":"27-37","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Immediate and delayed decrease of long term potentiation and memory deficits after neonatal intermittent hypoxia"],"prefix":"10.1002","volume":"74","author":[{"given":"Ivan","family":"Goussakov","sequence":"first","affiliation":[{"name":"Department of Pediatrics NorthShore University HealthSystem Research Institute 2650 Ridge Ave 60201 Evanston IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Synowiec","sequence":"additional","affiliation":[{"name":"Department of Pediatrics NorthShore University HealthSystem Research Institute 2650 Ridge Ave 60201 Evanston IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasily","family":"Yarnykh","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Washington 850 Republican St., Room 255 Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Drobyshevsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics NorthShore University HealthSystem Research Institute 2650 Ridge Ave 60201 Evanston IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,9]]},"reference":[{"issue":"10","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/ppul.20832","article-title":"Neonatal Apnea: what's new?","volume":"43","author":"Abu\u2010Shaweesh J.M.","year":"2008","journal-title":"Pediatr. Pulmonol."},{"issue":"5","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/opo.12131","article-title":"When to use the Bonferroni correction","volume":"34","author":"Armstrong R.A.","year":"2014","journal-title":"Ophthal. Physiol. Opt."},{"issue":"2","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1523\/JNEUROSCI.22-02-00455.2002","article-title":"Selective vulnerability of late oligodendrocyte progenitors to hypoxia\u2010ischemia","volume":"22","author":"Back S.A.","year":"2002","journal-title":"J. Neurosci."},{"issue":"7","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/nbm.783","article-title":"Diffusion\u2010tensor MRI: theory, experimental design and data analysis \u2010 a technical review","volume":"15","author":"Basser P.J.","year":"2002","journal-title":"NMR Biomed."},{"issue":"3","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1006\/jmrb.1994.1037","article-title":"Estimation of the effective self\u2010diffusion tensor from the NMR spin echo","volume":"103","author":"Basser P.J.","year":"1994","journal-title":"J. Magn. Reson. B"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3389\/fphys.2015.00313","article-title":"Protective effects of intermittent hypoxia on brain and memory in a mouse model of apnea of prematurity","volume":"6","author":"Bouslama M.","year":"2015","journal-title":"Front. Physiol."},{"issue":"2","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.resp.2011.06.003","article-title":"A neonatal mouse model of intermittent hypoxia associated with features of apnea in premature infants","volume":"178","author":"Cai J.","year":"2011","journal-title":"Respir. Physiol. Neurobiol."},{"issue":"3","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/path.2980","article-title":"Mouse intermittent hypoxia mimicking apnoea of prematurity: effects on myelinogenesis and axonal maturation","volume":"226","author":"Cai J.","year":"2012","journal-title":"J. Pathol."},{"issue":"1","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19010061","article-title":"Sexually dimorphic outcomes after neonatal stroke and hypoxia\u2010ischemia","volume":"19","author":"Charriaut\u2010Marlangue C.","year":"2017","journal-title":"Int. J. Mol. Sci."},{"issue":"9","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"R782","DOI":"10.1152\/ajpregu.00073.2013","article-title":"Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat","volume":"304","author":"Chintamaneni K.","year":"2013","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"5","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1152\/jn.1993.69.5.1774","article-title":"Anoxia\u2010induced LTP of isolated NMDA receptor\u2010mediated synaptic responses","volume":"69","author":"Crepel V.","year":"1993","journal-title":"J. Neurophysiol."},{"issue":"1","key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/pr.2017.102","article-title":"Early postnatal exposure to intermittent hypoxia in rodents is proinflammatory, impairs white matter integrity, and alters brain metabolism","volume":"82","author":"Darnall R.A.","year":"2017","journal-title":"Pediatr. Res."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.09.016"},{"issue":"2","key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/sj.jcbfm.9600333","article-title":"White matter injury correlates with hypertonia in an animal model of cerebral palsy","volume":"27","author":"Drobyshevsky A.","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"issue":"3","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1542\/peds.100.3.354","article-title":"Apnea frequently persists beyond term gestation in infants delivered at 24 to 28 weeks","volume":"100","author":"Eichenwald E.C.","year":"1997","journal-title":"Pediatrics"},{"issue":"7","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ijdevneu.2011.05.006","article-title":"Effects of birth asphyxia on neonatal hippocampal structure and function in the spiny mouse","volume":"29","author":"Fleiss B.","year":"2011","journal-title":"Int. J. Dev. Neurosci."},{"issue":"4","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jpeds.2004.05.039","article-title":"Sleep\u2010disordered breathing symptoms are associated with poorer cognitive function in 5\u2010year\u2010old children","volume":"145","author":"Gottlieb D.J.","year":"2004","journal-title":"J. Pediatr."},{"issue":"3","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0304-3940(01)01853-5","article-title":"Developmental differences in cortical and hippocampal vulnerability to intermittent hypoxia in the rat","volume":"305","author":"Gozal E.","year":"2001","journal-title":"Neurosci. Lett."},{"issue":"11","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0166-2236(94)90140-6","article-title":"Anoxic LTP sheds light on the multiple facets of NMDA receptors","volume":"17","author":"Hammond C.","year":"1994","journal-title":"Trends Neurosci."},{"issue":"1","key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1159\/000227293","article-title":"Behavioural effects of near\u2010term acute fetal hypoxia in a small precocial animal, the spiny mouse (Acomys cahirinus)","volume":"97","author":"Ireland Z.","year":"2010","journal-title":"Neonatology"},{"issue":"12","key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/sj.jp.7211182","article-title":"Apnea Is Associated with Neurodevelopmental Impairment in Very Low Birth Weight Infants","volume":"24","author":"Janvier A.","year":"2004","journal-title":"J. Perinatol."},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.11.010"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep46686"},{"issue":"8","key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"e0201829","DOI":"10.1371\/journal.pone.0201829","article-title":"Microbiota influence the development of the brain and behaviors in C57BL\/6J mice","volume":"13","author":"Lu J.","year":"2018","journal-title":"PLoS One"},{"issue":"1","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1152\/physrev.00014.2003","article-title":"Long\u2010term potentiation and memory","volume":"84","author":"Lynch M.A.","year":"2004","journal-title":"Physiol. Rev."},{"issue":"1","key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"e86576","DOI":"10.1371\/journal.pone.0086576","article-title":"Automatic structural parcellation of mouse brain MRI using multi\u2010atlas label fusion","volume":"9","author":"Ma D.","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.neuron.2004.09.012","article-title":"LTP and LTD: an embarrassment of riches","volume":"44","author":"Malenka R.C.","year":"2004","journal-title":"Neuron"},{"issue":"3","key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1159\/000329922","article-title":"Intermittent Hypoxic Episodes in Preterm Infants: Do They Matter?","volume":"100","author":"Martin R.J.","year":"2011","journal-title":"Neonatology"},{"issue":"11","key":"e_1_2_9_30_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0048828","article-title":"Non\u2010injurious neonatal hypoxia confers resistance to brain senescence in aged male rats","volume":"7","author":"Martin N.","year":"2012","journal-title":"PloS One"},{"key":"e_1_2_9_31_1","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0203-18.2018","article-title":"Myelination of axons corresponds with faster transmission speed in the prefrontal cortex of developing male rats","author":"McDougall S.","year":"2018","journal-title":"Eneuro"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.09.036"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100913-013101"},{"issue":"29","key":"e_1_2_9_34_1","doi-asserted-by":"crossref","first-page":"11863","DOI":"10.1523\/JNEUROSCI.0342-12.2013","article-title":"Spectrum of short\u2010 and long\u2010term brain pathology and long\u2010term behavioral deficits in male repeated hypoxic rats closely resembling human extreme prematurity","volume":"33","author":"Oorschot D.E.","year":"2013","journal-title":"J. Neurosci."},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1155\/2018\/9275239","article-title":"Cardiac arrest induces ischemic long\u2010term potentiation of hippocampal CA1 neurons that occludes physiological long\u2010term potentiation","volume":"2018","author":"Orfila J.E.","year":"2018","journal-title":"Neural Plasticity"},{"issue":"2","key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.brainres.2004.09.045","article-title":"Effect of intermittent hypoxia on long\u2010term potentiation in rat hippocampal slices","volume":"1029","author":"Payne R.S.","year":"2004","journal-title":"Brain Res."},{"issue":"3","key":"e_1_2_9_37_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000097446","article-title":"Factors influencing apnea and bradycardia of prematurity \u2010 implications for neurodevelopment","volume":"91","author":"Pillekamp F.","year":"2007","journal-title":"Neonatology"},{"issue":"49","key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"17800","DOI":"10.1523\/JNEUROSCI.6121-11.2012","article-title":"Glutamate receptor 1 phosphorylation at serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability after early life seizures","volume":"32","author":"Rakhade S.N.","year":"2012","journal-title":"J. Neurosci."},{"issue":"3","key":"e_1_2_9_39_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1203\/00006450-200209000-00024","article-title":"Impaired spatial learning and hyperactivity in developing rats exposed to intermittent hypoxia","volume":"52","author":"Row B.W.","year":"2002","journal-title":"Pediatr. Res."},{"issue":"6","key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1001\/jamapediatrics.2017.0238","article-title":"G. Caffeine for Apnea of prematurity trial, academic performance, motor function, and behavior 11 years after neonatal caffeine citrate therapy for apnea of prematurity: an 11\u2010year follow\u2010up of the cap randomized clinical trial","volume":"171","author":"Schmidt B.","year":"2017","journal-title":"JAMA Pediatr."},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.08.054"},{"issue":"3","key":"e_1_2_9_42_1","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/j.neuroimage.2010.10.065","article-title":"Fast bound pool fraction imaging of the in vivo rat brain: association with myelin content and validation in the C6 glioma model","volume":"54","author":"Underhill H.R.","year":"2011","journal-title":"Neuroimage"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2013.07.008"},{"issue":"1","key":"e_1_2_9_44_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.nbd.2010.05.020","article-title":"Brain\u2010derived neurotrophic factor rescues and prevents chronic intermittent hypoxia\u2010induced impairment of hippocampal long\u2010term synaptic plasticity","volume":"40","author":"Xie H.","year":"2010","journal-title":"Neurobiol. Dis."},{"issue":"1","key":"e_1_2_9_45_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/mrm.21120","article-title":"Actual flip\u2010angle imaging in the pulsed steady state: a method for rapid three\u2010dimensional mapping of the transmitted radiofrequency field","volume":"57","author":"Yarnykh V.L.","year":"2007","journal-title":"Magn. Reson. Med."},{"issue":"5","key":"e_1_2_9_46_1","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1002\/mrm.25811","article-title":"Time\u2010efficient, high\u2010resolution, whole brain three\u2010dimensional macromolecular proton fraction mapping","volume":"75","author":"Yarnykh V.L.","year":"2016","journal-title":"Mag. Reson. Med."},{"issue":"1","key":"e_1_2_9_47_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1148\/radiol.14140528","article-title":"Fast whole\u2010brain three\u2010dimensional macromolecular proton fraction mapping in multiple sclerosis","volume":"274","author":"Yarnykh V.L.","year":"2015","journal-title":"Radiology"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.09.046"},{"issue":"1","key":"e_1_2_9_49_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/neu.20174","article-title":"Neonatal exposure to intermittent hypoxia enhances mice performance in water maze and 8\u2010arm radial maze tasks","volume":"65","author":"Zhang J.X.","year":"2005","journal-title":"J. Neurobiol."}],"container-title":["International Journal of Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0736574818303496?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0736574818303496?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.ijdevneu.2019.03.001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ijdevneu.2019.03.001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.ijdevneu.2019.03.001","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ijdevneu.2019.03.001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T18:11:41Z","timestamp":1694023901000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1016\/j.ijdevneu.2019.03.001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,9]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1016\/j.ijdevneu.2019.03.001"],"URL":"https:\/\/doi.org\/10.1016\/j.ijdevneu.2019.03.001","archive":["Portico"],"relation":{},"ISSN":["0736-5748","1873-474X"],"issn-type":[{"value":"0736-5748","type":"print"},{"value":"1873-474X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,9]]},"assertion":[{"value":"2018-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}