{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:31:04Z","timestamp":1766035864379,"version":"3.48.0"},"reference-count":44,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007527","name":"Rouen University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007527","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["#UMR1245"],"award-info":[{"award-number":["#UMR1245"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Rouen University Hospital"},{"name":"M\u00e9tropole Rouen Normandy","award":["#010535"],"award-info":[{"award-number":["#010535"]}]},{"name":"M\u00e9tropole Rouen Normandy","award":["#013362"],"award-info":[{"award-number":["#013362"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perinatal asphyxia (PA) remains a common cause of neonatal death and long-term disability, with an incidence of 20 per 1000 live births. Even mild PA, without significant neurological distress at birth, is linked to neurodevelopmental disorders. Premature babies are at high risk for both PA and long-term neurobehavioral deficits. The use of peripherally inserted central venous catheters in neonatal intensive care units has reduced mortality and morbidity in preterms. Given their prevalent use and associated complications, such as thrombosis, the present study aimed to investigate the effects of hypoxia associated with the ligation of the external jugular vein (JH model) in 5-day-old mice, whose central nervous system development shares similarities with that of human preterms. Diffuse white matter (WM) injury is associated with later neurodisabilities following very premature birth before 32 weeks of gestation. The present study aimed to investigate whether the murine JH model replicates a key phenotype of non-cystic WM injury, namely permanent hypomyelination and sensorimotor deficits. The second aim was to determine whether sodium phenylbutyrate (PBA), which is already prescribed in neonates for another indication, could prevent these disabilities. JH induced lasting dysmyelination in males, not prevented by PBA, contrary to the discrete JH-induced neurobehavioral deficits observed in both sexes in the short and long term.<\/jats:p>","DOI":"10.3390\/ijms262412099","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:47:26Z","timestamp":1765889246000},"page":"12099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short- and Long-Term Effects of Sodium Phenylbutyrate on White Matter and Sensorimotor and Cognitive Behavior in a Mild Murine Model of Encephalopathy of Prematurity"],"prefix":"10.3390","volume":"26","author":[{"given":"Marie-Anne","family":"Le Ray","sequence":"first","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyann","family":"Larralde","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lou","family":"Legouez","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-148X","authenticated-orcid":false,"given":"St\u00e9phane","family":"Marret","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, F-76000 Rouen, France"},{"name":"Univ Rouen Normandie, Inserm U1245 and CHU Rouen, Department of P\u00e9diatrie N\u00e9onatale et R\u00e9animation, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Baptiste","family":"Muller","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, F-76000 Rouen, France"},{"name":"Univ Rouen Normandie, Inserm U1245 and CHU Rouen, Department of P\u00e9diatrie N\u00e9onatale et R\u00e9animation, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7176-1320","authenticated-orcid":false,"given":"Bruno J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine","family":"Cleren","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Inserm U1245, F-76000 Rouen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/glia.23256","article-title":"Origin and Dynamics of Oligodendrocytes in the Developing Brain: Implications for Perinatal White Matter Injury","volume":"66","author":"Wagenaar","year":"2018","journal-title":"Glia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/glia.24474","article-title":"Key Roles of Glial Cells in the Encephalopathy of Prematurity","volume":"72","author":"Bokobza","year":"2024","journal-title":"Glia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.pediatrneurol.2015.04.006","article-title":"Brain Injury in the Preterm Infant: New Horizons for Pathogenesis and Prevention","volume":"53","author":"Back","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12974-014-0197-0","article-title":"The Effect of Osteopontin and Osteopontin-Derived Peptides on Preterm Brain Injury","volume":"11","author":"Albertsson","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1111\/ejn.14664","article-title":"Why Considering Sexual Differences Is Necessary When Studying Encephalopathy of Prematurity through Rodent Models","volume":"52","author":"Legouez","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0095-5108(18)31180-1","article-title":"Respiratory Distress in Newborns","volume":"5","author":"Boyle","year":"1978","journal-title":"Clin. Perinatol."},{"key":"ref_7","first-page":"987","article-title":"Respiratory Distress in the Newborn","volume":"76","author":"Hermansen","year":"2007","journal-title":"Am. Fam. Physician"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1111\/dmcn.15234","article-title":"Early-Life Respiratory Trajectories and Neurodevelopmental Outcomes in Infants Born Very and Extremely Preterm: A Retrospective Study","volume":"64","author":"Yu","year":"2022","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/JPN.0000000000000589","article-title":"Neonatal Vascular Access Practice and Complications: An Observational Study of 1375 Catheter Days","volume":"37","author":"McIntyre","year":"2023","journal-title":"J. Perinat. Neonatal Nurs."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1097\/MBC.0b013e328364f9b0","article-title":"Neonatal Central Venous Catheter Thrombosis: Diagnosis, Management and Outcome","volume":"25","author":"Park","year":"2014","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s40272-014-0081-5","article-title":"Results from a Nationwide Cohort Temporary Utilization Authorization (ATU) Survey of Patients in France Treated with Pheburane\u00ae (Sodium Phenylbutyrate) Taste-Masked Granules","volume":"16","author":"Kibleur","year":"2014","journal-title":"Paediatr. Drugs"},{"key":"ref_12","unstructured":"Haute Autorit\u00e9 de Sant\u00e9 (HAS) (2014, January 22). Evaluation Report: Pheburane\u00ae (Sodium Phenylbutyrate). Opinion Issued. Available online: https:\/\/www.has-sante.fr\/jcms\/c_1720968\/fr\/pheburane-phenylbutyrate-de-sodium."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e477","DOI":"10.1097\/CCM.0000000000001469","article-title":"4-Phenylbutyrate Benefits Traumatic Hemorrhagic Shock in Rats by Attenuating Oxidative Stress, Not by Attenuating Endoplasmic Reticulum Stress","volume":"44","author":"Yang","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1124\/mol.104.001339","article-title":"Sodium 4-Phenylbutyrate Protects against Cerebral Ischemic Injury","volume":"66","author":"Qi","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5105","DOI":"10.2174\/1381612811319280009","article-title":"Potential Roles of HDAC Inhibitors in Mitigating Ischemia-Induced Brain Damage and Facilitating Endogenous Regeneration and Recovery","volume":"19","author":"Fessler","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1007\/s12035-016-0149-z","article-title":"HDAC Inhibitor Sodium Butyrate-Mediated Epigenetic Regulation Enhances Neuroprotective Function of Microglia during Ischemic Stroke","volume":"54","author":"Patnala","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Roy, A., Ghosh, A., Jana, A., Liu, X., Brahmachari, S., Gendelman, H.E., and Pahan, K. (2012). Sodium Phenylbutyrate Controls Neuroinflammatory and Antioxidant Activities and Protects Dopaminergic Neurons in Mouse Models of Parkinson\u2019s Disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038113"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Legouez, L., Le Dieu-Lugon, B., Feillet, S., Riou, G., Yeddou, M., Plouchart, T., Dourmap, N., Le Ray, M.A., Marret, S., and Gonzalez, B.J. (2022). Effects of MgSO4 Alone or Associated with 4-PBA on Behavior and White Matter Integrity in a Mouse Model of Cerebral Palsy: A Sex- and Time-Dependent Study. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415947"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Thabault, M., Turpin, V., Maisterrena, A., Jaber, M., Egloff, M., and Galvan, L. (2022). Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042294"},{"key":"ref_20","first-page":"e55261","article-title":"Neurodevelopmental Reflex Testing in Neonatal Rat Pups","volume":"122","author":"Nguyen","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_21","first-page":"e53569","article-title":"A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy","volume":"117","author":"Ferguson","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_22","unstructured":"Benezit, A., Hertz-Pannier, L., Dehaene-Lambertz, G., and Dubois, J. (2011). Le Corps Calleux: Sa Vie Pr\u00e9coce, Son \u0152uvre Tardive. Les Malformations Cong\u00e9nitales\u2014Diagnostic Ant\u00e9natal et Devenir, Tome 6, Sauramps Medical."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1038\/s41598-024-52277-z","article-title":"A Systematic Review and Meta-Analysis of How Social Memory Is Studied","volume":"14","author":"Cum","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_24","first-page":"e2376","article-title":"Assessment of Motor Balance and Coordination in Mice Using the Balance Beam","volume":"49","author":"Luong","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Martins, L.A., Schiavo, A., Xavier, L.L., and Mestriner, R.G. (2022). The Foot Fault Scoring System to Assess Skilled Walking in Rodents: A Reliability Study. Front. Behav. Neurosci., 16.","DOI":"10.3389\/fnbeh.2022.892010"},{"key":"ref_26","first-page":"e55718","article-title":"Novel Object Recognition Test for the Investigation of Learning and Memory in Mice","volume":"126","author":"Lueptow","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_27","unstructured":"Paxinos, G., Halliday, G., Watson, C., and Kassem, M.S. (2020). Atlas of the Developing Mouse Brain, Academic Press. [2nd ed.]."},{"key":"ref_28","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","year":"2012","journal-title":"J. Pathol."},{"key":"ref_29","first-page":"1","article-title":"Inflammatory Mechanisms Contribute to Long-Term Cognitive Deficits Induced by Perinatal Asphyxia via Interleukin 1","volume":"50","author":"Kelemen","year":"2025","journal-title":"Neuropsychopharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7465","DOI":"10.1523\/JNEUROSCI.2738-16.2017","article-title":"The Integrated Stress Response in Hypoxia-Induced Diffuse White Matter Injury","volume":"37","author":"Clayton","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.expneurol.2014.11.010","article-title":"Mild Intermittent Hypoxemia in Neonatal Mice Causes Permanent Neurofunctional Deficit and White Matter Hypomyelination","volume":"264","author":"Juliano","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4103\/1673-5374.314301","article-title":"Hypoxia Inducible Factor and Diffuse White Matter Injury in the Premature Brain: Perspectives from Genetic Studies in Mice","volume":"17","author":"Guo","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.brainres.2017.11.005","article-title":"Histone Acetylation of Oligodendrocytes Protects against White Matter Injury Induced by Inflammation and Hypoxia-Ischemia through Activation of BDNF-TrkB Signaling Pathway in Neonatal Rats","volume":"1688","author":"Huang","year":"2018","journal-title":"Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.brainres.2016.05.040","article-title":"Dose-Dependent Effects of Levetiracetam after Hypoxia and Hypothermia in the Neonatal Mouse Brain","volume":"1646","author":"Strasser","year":"2016","journal-title":"Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.neuroscience.2014.08.019","article-title":"Pharmacologic Stabilization of Hypoxia-Inducible Transcription Factors Protects Developing Mouse Brain from Hypoxia-Induced Apoptotic Cell Death","volume":"278","author":"Trollmann","year":"2014","journal-title":"Neuroscience"},{"key":"ref_36","first-page":"127","article-title":"The Neonatal Testosterone Surge: A Comparative Study","volume":"100","author":"Corbier","year":"1992","journal-title":"Arch. Int. Physiol. Biochim. Biophys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R1105","DOI":"10.1152\/ajpregu.00535.2005","article-title":"Effect of Chronic Continuous or Intermittent Hypoxia and Reoxygenation on Cerebral Capillary Density and Myelination","volume":"290","author":"Kanaan","year":"2006","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_38","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","year":"2017","journal-title":"Pediatr. Res."},{"key":"ref_39","first-page":"447","article-title":"Formation, Maturation, and Disorders of White Matter","volume":"13","author":"Barkovich","year":"1992","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0306-4522(01)00171-3","article-title":"Translating Developmental Time Across Mammalian Species","volume":"105","author":"Clancy","year":"2001","journal-title":"Neuroscience"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tiane, A., Schepers, M., Rombaut, B., Hupperts, R., Prickaerts, J., Hellings, N., van den Hove, D., and Vanmierlo, T. (2019). From OPC to Oligodendrocyte: An Epigenetic Journey. Cells, 8.","DOI":"10.3390\/cells8101236"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Abi Ghanem, C., Degerny, C., Hussain, R., Liere, P., Pianos, A., Tourpin, S., Habert, R., Macklin, W.B., Schumacher, M., and Ghoumari, A.M. (2017). Long-Lasting Masculinizing Effects of Postnatal Androgens on Myelin Governed by the Brain Androgen Receptor. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1007049"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1161\/STROKEAHA.114.005324","article-title":"Recognition Memory Impairments after Subcortical White Matter Stroke in Mice","volume":"45","author":"Blasi","year":"2014","journal-title":"Stroke"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.pneurobio.2009.01.003","article-title":"Periventricular White Matter Damage in the Hypoxic Neonatal Brain: Role of Microglial Cells","volume":"87","author":"Kaur","year":"2009","journal-title":"Prog. Neurobiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12099\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:28:26Z","timestamp":1766035706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":44,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262412099"],"URL":"https:\/\/doi.org\/10.3390\/ijms262412099","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,12,16]]}}}