{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:51:21Z","timestamp":1791309081903,"version":"4.3.1"},"reference-count":89,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"NIH","award":["R01NS117428"],"award-info":[{"award-number":["R01NS117428"]}]},{"name":"ANR","award":["ANR-21-CE17-0019-01"],"award-info":[{"award-number":["ANR-21-CE17-0019-01"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharm Res"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1007\/s11095-026-04163-8","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:49:50Z","timestamp":1785365390000},"page":"3173-3191","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Brain Distribution of a Purine-Derived Neuroprotective Agent after Intranasal Administration in Neonatal Rats with Hypoxic\u2013Ischemic Brain Injury"],"prefix":"10.1007","volume":"43","author":[{"given":"Auriane","family":"Ma\u00efza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemence","family":"Disdier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Tsintzou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anvi Laetitia","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Pruvost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Th\u00e9odoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexi","family":"Zang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nassima","family":"Oumata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Galons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara S.","family":"Stonestreet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alo\u00efse","family":"Mabondzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-2814","authenticated-orcid":false,"given":"Xiaodi F.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"issue":"8","key":"4163_CR1","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.ijdevneu.2009.05.009","volume":"27","author":"J Scafidi","year":"2009","unstructured":"Scafidi J, Fagel DM, Ment LR, Vaccarino FM. Modeling premature brain injury and recovery. Int J Dev Neurosci. 2009;27(8):863\u201371.","journal-title":"Int J Dev Neurosci"},{"key":"4163_CR2","doi-asserted-by":"crossref","unstructured":"Fatemi A, Wilson MA, Johnston MV. Hypoxic-ischemic encephalopathy in the term infant. Clin Perinatol. 2009;36(4):835\u2013858, vii.","DOI":"10.1016\/j.clp.2009.07.011"},{"issue":"3","key":"4163_CR3","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/bdrc.20095","volume":"81","author":"RD Barrett","year":"2007","unstructured":"Barrett RD, Bennet L, Davidson J, Dean JM, George S, Emerald BS, Gunn AJ. Destruction and reconstruction: hypoxia and the developing brain. Birth Defects Res C Embryo Today. 2007;81(3):163\u201376.","journal-title":"Birth Defects Res C Embryo Today"},{"key":"4163_CR4","unstructured":"Honeycutt A, Dunlap L, Chen H, Homsi G, Grosse S, Schendel D. Economic costs associated with mental retardation, cerebral palsy, hearing loss, and vision impairment - - - United States, 2003. In: Morbidity and Mortality Weekly Report. 2004:57\u20139."},{"issue":"1","key":"4163_CR5","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1089\/ther.2016.0018","volume":"7","author":"AC Klahr","year":"2017","unstructured":"Klahr AC, Nadeau CA, Colbourne F. Temperature control in rodent neuroprotection studies: methods and challenges. Ther Hypothermia Temp Manag. 2017;7(1):42\u20139.","journal-title":"Ther Hypothermia Temp Manag"},{"issue":"2","key":"4163_CR6","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1586\/eog.10.7","volume":"5","author":"CM Cotten","year":"2010","unstructured":"Cotten CM, Shankaran S. Hypothermia for hypoxic-ischemic encephalopathy. Expert Rev Obstet Gynecol. 2010;5(2):227\u201339.","journal-title":"Expert Rev Obstet Gynecol"},{"issue":"4","key":"4163_CR7","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.resuscitation.2013.12.006","volume":"85","author":"D Osredkar","year":"2014","unstructured":"Osredkar D, Thoresen M, Maes E, Flatebo T, Elstad M, Sabir H. Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxic-ischemic brain injury. Resuscitation. 2014;85(4):567\u201372.","journal-title":"Resuscitation"},{"key":"4163_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2016.00057","volume":"7","author":"P Rumajogee","year":"2016","unstructured":"Rumajogee P, Bregman T, Miller SP, Yager JY, Fehlings MG. Rodent hypoxia-ischemia models for cerebral palsy research: a systematic review. Front Neurol. 2016;7: 57.","journal-title":"Front Neurol"},{"key":"4163_CR9","unstructured":"Sakr M, Shah M, Balasundaram P. Neonatal therapeutic hypothermia. In. StatPearls. Treasure Island (FL). 2024.\u00a0https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33620791."},{"key":"4163_CR10","doi-asserted-by":"crossref","unstructured":"Molloy EJ, El-Dib M, Juul SE, Benders M, Gonzalez F, Bearer C, et al. Neuroprotective therapies in the NICU in term infants: present and future. Pediatr Res. 2023;93(7):1819\u201327.","DOI":"10.1038\/s41390-022-02295-2"},{"issue":"4","key":"4163_CR11","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1001\/jamapediatrics.2024.6613","volume":"179","author":"RG Faix","year":"2025","unstructured":"Faix RG, Laptook AR, Shankaran S, Eggleston B, Chowdhury D, Heyne RJ, Das A, Pedroza C, Tyson JE, Wusthoff C, Bonifacio SL, Sanchez PJ, Yoder BA, Laughon MM, Vasil DM, Van Meurs KP, Crawford MM, Higgins RD, Poindexter BB, Colaizy TT, Hamrick SEG, Chalak LF, Ohls RK, Hartley-McAndrew ME, Dysart K, D\u2019Angio CT, Guillet R, Kicklighter SD, Carlo WA, Sokol GM, DeMauro SB, Hibbs AM, Cotten CM, Merhar SL, Bapat RV, Harmon HM, Sewell E, Winter S, Natarajan G, Mosquera R, Hintz SR, Maitre NL, Benninger KL, Peralta-Carcelen M, Hines AC, Duncan AF, Wilson-Costello DE, Trembath A, Malcolm WF, Walsh MC, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Whole-Body Hypothermia for Neonatal Encephalopathy in Preterm Infants 33 to 35 Weeks\u2019 Gestation: A Randomized Clinical Trial. JAMA Pediatr. 2025;179(4):396\u2013406.","journal-title":"JAMA Pediatr"},{"issue":"23","key":"4163_CR12","doi-asserted-by":"publisher","first-page":"5655","DOI":"10.1113\/JP274938","volume":"596","author":"C Mallard","year":"2018","unstructured":"Mallard C, Ek CJ, Vexler ZS. The myth of the immature barrier systems in the developing brain: role in perinatal brain injury. J Physiol. 2018;596(23):5655\u201364.","journal-title":"J Physiol"},{"key":"4163_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00046","volume":"3","author":"NR Saunders","year":"2012","unstructured":"Saunders NR, Liddelow SA, Dziegielewska KM. Barrier mechanisms in the developing brain. Front Pharmacol. 2012;3: 46.","journal-title":"Front Pharmacol"},{"issue":"6 Pt 2","key":"4163_CR14","first-page":"R1594","volume":"271","author":"BS Stonestreet","year":"1996","unstructured":"Stonestreet BS, Patlak CS, Pettigrew KD, Reilly CB, Cserr HF. Ontogeny of blood-brain barrier function in ovine fetuses, lambs, and adults. Am J Physiol. 1996;271(6 Pt 2):R1594-1601.","journal-title":"Am J Physiol"},{"issue":"28","key":"4163_CR15","doi-asserted-by":"publisher","first-page":"9588","DOI":"10.1523\/JNEUROSCI.5977-11.2012","volume":"32","author":"D Fernandez-Lopez","year":"2012","unstructured":"Fernandez-Lopez D, Faustino J, Daneman R, Zhou L, Lee SY, Derugin N, Wendland MF, Vexler ZS. Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat. J Neurosci. 2012;32(28):9588\u2013600.","journal-title":"J Neurosci"},{"key":"4163_CR16","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.lfs.2017.12.025","volume":"195","author":"TP Crowe","year":"2018","unstructured":"Crowe TP, Greenlee MHW, Kanthasamy AG, Hsu WH. Mechanism of intranasal drug delivery directly to the brain. Life Sci. 2018;195:44\u201352.","journal-title":"Life Sci"},{"issue":"7","key":"4163_CR17","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.addr.2011.11.002","volume":"64","author":"JJ Lochhead","year":"2012","unstructured":"Lochhead JJ, Thorne RG. Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev. 2012;64(7):614\u201328.","journal-title":"Adv Drug Deliv Rev"},{"key":"4163_CR18","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/978-3-030-88773-5_15","volume-title":"Drug delivery to the brain: physiological concepts, methodologies and approaches","author":"JJ Lochhead","year":"2022","unstructured":"Lochhead JJ, Kumar NN, Nehra G, Stenslik MJ, Bradley LH, Thorne RG. Intranasal drug delivery to the brain. In: de Lange ECM, Hammarlund-Udenaes M, Thorne RG, editors. Drug delivery to the brain: physiological concepts, methodologies and approaches. Cham: Springer International Publishing; 2022. p. 461\u2013500."},{"issue":"1-2","key":"4163_CR19","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/S0378-5173(03)00039-5","volume":"255","author":"C Dufes","year":"2003","unstructured":"Dufes C, Olivier JC, Gaillard F, Gaillard A, Couet W, Muller JM. Brain delivery of vasoactive intestinal peptide (VIP) following nasal administration to rats. Int J Pharm. 2003;255(1\u20132):87\u201397.","journal-title":"Int J Pharm"},{"key":"4163_CR20","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.brainresbull.2018.10.009","volume":"143","author":"F Erd\u0151","year":"2018","unstructured":"Erd\u0151 F, Bors LA, Farkas D, Bajza \u00c1, Gizurarson S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res Bull. 2018;143:155\u201370.","journal-title":"Brain Res Bull"},{"issue":"(Suppl 3)","key":"4163_CR21","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1186\/1471-2202-9-S3-S5","volume":"9","author":"LR Hanson","year":"2008","unstructured":"Hanson LR, Frey WH 2nd. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci. 2008;9((Suppl 3)):S5.","journal-title":"BMC Neurosci"},{"key":"4163_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1341295","volume":"15","author":"Q Huang","year":"2023","unstructured":"Huang Q, Chen X, Yu S, Gong G, Shu H. Research progress in brain-targeted nasal drug delivery. Front Aging Neurosci. 2023;15: 1341295.","journal-title":"Front Aging Neurosci"},{"key":"4163_CR23","doi-asserted-by":"publisher","first-page":"638136","DOI":"10.3389\/falgy.2021.638136","volume":"2","author":"C Cingi","year":"2021","unstructured":"Cingi C, Bayar Muluk N, Mitsias DI, Papadopoulos NG, Klimek L, Laulajainen-Hongisto A, Hytonen M, Toppila-Salmi SK, Scadding GK. The Nose as a Route for Therapy: Part 1. Pharmacotherapy Front Allergy. 2021;2:638136.","journal-title":"Pharmacotherapy Front Allergy"},{"issue":"3","key":"4163_CR24","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1248\/bpb.30.608","volume":"30","author":"T Furubayashi","year":"2007","unstructured":"Furubayashi T, Kamaguchi A, Kawaharada K, Masaoka Y, Kataoka M, Yamashita S, Higashi Y, Sakane T. Evaluation of the contribution of the nasal cavity and gastrointestinal tract to drug absorption following nasal application to rats. Biol Pharm Bull. 2007;30(3):608\u201311.","journal-title":"Biol Pharm Bull"},{"issue":"4","key":"4163_CR25","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1097\/JNN.0000000000000769","volume":"56","author":"PO Shafer","year":"2024","unstructured":"Shafer PO, Dean P, Brooks L, Gidal B, Misra SN, Carrazana E. Intranasal delivery of medications for the treatment of neurologic conditions: a pharmacology update. J Neurosci Nurs. 2024;56(4):136\u201342.","journal-title":"J Neurosci Nurs"},{"key":"4163_CR26","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00376","volume":"12","author":"CI Tasca","year":"2018","unstructured":"Tasca CI, Lanznaster D, Oliveira KA, Fernandez-Duenas V, Ciruela F. Neuromodulatory effects of guanine-based purines in health and disease. Front Cell Neurosci. 2018;12: 376.","journal-title":"Front Cell Neurosci"},{"issue":"6","key":"4163_CR27","doi-asserted-by":"publisher","first-page":"541","DOI":"10.2174\/0115680266290152240110074034","volume":"24","author":"N Rana","year":"2024","unstructured":"Rana N, Grover P, Singh H. Recent developments and future perspectives of purine derivatives as a promising scaffold in drug discovery. Curr Top Med Chem. 2024;24(6):541\u201379.","journal-title":"Curr Top Med Chem"},{"issue":"6","key":"4163_CR28","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/S0301-0082(99)00017-9","volume":"59","author":"MP Rathbone","year":"1999","unstructured":"Rathbone MP, Middlemiss PJ, Gysbers JW, Andrew C, Herman MA, Reed JK, Ciccarelli R, Di Iorio P, Caciagli F. Trophic effects of purines in neurons and glial cells. Prog Neurobiol. 1999;59(6):663\u201390.","journal-title":"Prog Neurobiol"},{"key":"4163_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00941","volume":"8","author":"M Fumagalli","year":"2017","unstructured":"Fumagalli M, Lecca D, Abbracchio MP, Ceruti S. Pathophysiological role of purines and pyrimidines in neurodevelopment: unveiling new pharmacological approaches to congenital brain diseases. Front Pharmacol. 2017;8: 941.","journal-title":"Front Pharmacol"},{"key":"4163_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713067","author":"N Matsumura","year":"2023","unstructured":"Matsumura N, Aoyama K. Glutathione-mediated neuroprotective effect of purine derivatives. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms241713067.","journal-title":"Int J Mol Sci"},{"issue":"4","key":"4163_CR31","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.1021\/acs.jmedchem.0c02145","volume":"64","author":"F Calzaferri","year":"2021","unstructured":"Calzaferri F, Narros-Fernandez P, de Pascual R, de Diego AMG, Nicke A, Egea J, Garcia AG, de Los Rios C. Synthesis and pharmacological evaluation of novel non-nucleotide purine derivatives as P2X7 antagonists for the treatment of neuroinflammation. J Med Chem. 2021;64(4):2272\u201390.","journal-title":"J Med Chem"},{"issue":"8","key":"4163_CR32","doi-asserted-by":"publisher","first-page":"961","DOI":"10.4155\/tde.15.32","volume":"6","author":"WJ Geldenhuys","year":"2015","unstructured":"Geldenhuys WJ, Mohammad AS, Adkins CE, Lockman PR. Molecular determinants of blood-brain barrier permeation. Ther Deliv. 2015;6(8):961\u201371.","journal-title":"Ther Deliv"},{"issue":"11","key":"4163_CR33","doi-asserted-by":"publisher","first-page":"7253","DOI":"10.1021\/acs.jmedchem.2c01824","volume":"66","author":"FMG Cornelissen","year":"2023","unstructured":"Cornelissen FMG, Markert G, Deutsch G, Antonara M, Faaij N, Bartelink I, Noske D, Vandertop WP, Bender A, Westerman BA. Explaining blood-brain barrier permeability of small molecules by integrated analysis of different transport mechanisms. J Med Chem. 2023;66(11):7253\u201367.","journal-title":"J Med Chem"},{"issue":"1","key":"4163_CR34","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1038\/s41598-020-57560-3","volume":"10","author":"AC Guyot","year":"2020","unstructured":"Guyot AC, Leuxe C, Disdier C, Oumata N, Costa N, Roux GL, Varela PF, Duchon A, Charbonnier JB, Herault Y, Pavoni S, Galons H, Andriambeloson E, Wagner S, Meijer L, Lund AK, Mabondzo A. A small compound targeting prohibitin with potential interest for cognitive deficit rescue in aging mice and tau pathology treatment. Sci Rep. 2020;10(1):1143.","journal-title":"Sci Rep"},{"issue":"5","key":"4163_CR35","first-page":"600","volume":"50","author":"PV Turner","year":"2011","unstructured":"Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci. 2011;50(5):600\u201313.","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"4163_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2025.e00621","author":"A Mabondzo","year":"2025","unstructured":"Mabondzo A, Disdier C, Bouzid A, Larbi KS, Tsintzou A, Maiza A, Kim B, Costa N, Harati R, Nguyen AL, Pruvost A, Galons H, Oumata N, Armengaud J, Knijnenburg M, Verma G, Hagberg H, Gressens P, Chen XF, Hamoudi RA, Stonestreet BS. Novel purine derivatives mitigate hypoxia ischemia related brain injury through agrin, zyxin and synaptotagmin proteins. Neurotherapeutics. 2025. https:\/\/doi.org\/10.1016\/j.neurot.2025.e00621.","journal-title":"Neurotherapeutics"},{"issue":"2","key":"4163_CR37","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/ana.410090206","volume":"9","author":"JE Rice","year":"1981","unstructured":"Rice JE, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain-damage in the rat. Ann Neurol. 1981;9(2):131\u201341.","journal-title":"Ann Neurol"},{"key":"4163_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/life12101514","author":"R McLeod","year":"2022","unstructured":"McLeod R, Rosenkrantz T, Fitch RH. Therapeutic interventions in rat models of preterm hypoxic ischemic injury: effects of hypothermia, caffeine, and the influence of sex. Life. 2022. https:\/\/doi.org\/10.3390\/life12101514.","journal-title":"Life"},{"issue":"3","key":"4163_CR39","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/pr.2015.100","volume":"78","author":"SD Patel","year":"2015","unstructured":"Patel SD, Pierce L, Ciardiello A, Hutton A, Paskewitz S, Aronowitz E, Voss HU, Moore H, Vannucci SJ. Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: characterization of a translational preclinical model. Pediatr Res. 2015;78(3):264\u201371.","journal-title":"Pediatr Res"},{"key":"4163_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","volume":"106-107","author":"BD Semple","year":"2013","unstructured":"Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ. Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol. 2013;106\u2013107:1\u201316.","journal-title":"Prog Neurobiol"},{"issue":"17","key":"4163_CR41","doi-asserted-by":"publisher","first-page":"7368","DOI":"10.1523\/JNEUROSCI.5746-12.2013","volume":"33","author":"AD Workman","year":"2013","unstructured":"Workman AD, Charvet CJ, Clancy B, Darlington RB, Finlay BL. Modeling transformations of neurodevelopmental sequences across mammalian species. J Neurosci. 2013;33(17):7368\u201383.","journal-title":"J Neurosci"},{"key":"4163_CR42","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.neuroscience.2018.01.023","volume":"405","author":"C Mallard","year":"2019","unstructured":"Mallard C, Tremblay ME, Vexler ZS. Microglia and neonatal brain injury. Neuroscience. 2019;405:68\u201376.","journal-title":"Neuroscience"},{"issue":"1-2","key":"4163_CR43","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.bbr.2003.08.018","volume":"151","author":"K Mishima","year":"2004","unstructured":"Mishima K, Ikeda T, Yoshikawa T, Aoo N, Egashira N, Xia YX, Ikenoue T, Iwasaki K, Fujiwara M. Effects of hypothermia and hyperthermia on attentional and spatial learning deficits following neonatal hypoxia-ischemic insult in rats. Behav Brain Res. 2004;151(1\u20132):209\u201317.","journal-title":"Behav Brain Res"},{"key":"4163_CR44","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.expneurol.2016.06.024","volume":"283","author":"BS Reinboth","year":"2016","unstructured":"Reinboth BS, Koster C, Abberger H, Prager S, Bendix I, Felderhoff-Muser U, Herz J. Endogenous hypothermic response to hypoxia reduces brain injury: implications for modeling hypoxic-ischemic encephalopathy and therapeutic hypothermia in neonatal mice. Exp Neurol. 2016;283:264\u201375.","journal-title":"Exp Neurol"},{"key":"4163_CR45","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jped.2015.07.004","volume":"91","author":"RC Silveira","year":"2015","unstructured":"Silveira RC, Procianoy RS. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy. J Pediatr (Rio J). 2015;91:78\u201383.","journal-title":"J Pediatr (Rio J)"},{"issue":"8","key":"4163_CR46","first-page":"494","volume":"12","author":"K Marks","year":"2010","unstructured":"Marks K, Shany E, Shelef I, Golan A, Zmora E. Hypothermia: A Neuroprotective Therapy for Neonatal Hypoxic Ischemic Encephalopathy. Israel Med Assoc J. 2010;12(8):494\u2013500.","journal-title":"Israel Med Assoc J"},{"issue":"4","key":"4163_CR47","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/jcbfm.2008.163","volume":"29","author":"M Thoresen","year":"2009","unstructured":"Thoresen M, Hobbs CE, Wood T, Chakkarapani E, Dingley J. Cooling combined with immediate or delayed xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia. J Cereb Blood Flow Metab. 2009;29(4):707\u201314.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"4163_CR48","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1172\/JCI200418336","volume":"113","author":"L Zhang","year":"2004","unstructured":"Zhang L, Nair A, Krady K, Corpe C, Bonneau RH, Simpson IA, Vannucci SJ. Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice. J Clin Invest. 2004;113(1):85\u201395.","journal-title":"J Clin Invest"},{"key":"4163_CR49","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.expneurol.2019.03.013","volume":"317","author":"X Chen","year":"2019","unstructured":"Chen X, Nakada S, Donahue JE, Chen RH, Tucker R, Qiu J, Lim YP, Stopa EG, Stonestreet BS. Neuroprotective effects of inter-alpha inhibitor proteins after hypoxic-ischemic brain injury in neonatal rats. Exp Neurol. 2019;317:244\u201359.","journal-title":"Exp Neurol"},{"key":"4163_CR50","doi-asserted-by":"publisher","first-page":"115151","DOI":"10.1016\/j.expneurol.2025.115151","volume":"386","author":"XF Chen","year":"2025","unstructured":"Chen XF, Kroke B, Ni J, Munoz C, Appleman M, Jacobs B, Tran T, Nguyen KV, Qiu C, Stonestreet BS, Marshall J. Novel peptidomimetic compounds attenuate hypoxic-ischemic brain injury in neonatal rats. Exp Neurol. 2025;386:115151.","journal-title":"Exp Neurol"},{"issue":"1","key":"4163_CR51","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1161\/01.STR.24.1.117","volume":"24","author":"TN Lin","year":"1993","unstructured":"Lin TN, He YY, Wu G, Khan M, Hsu CY. Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke. 1993;24(1):117\u201321.","journal-title":"Stroke"},{"issue":"2","key":"4163_CR52","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/jcbfm.1990.47","volume":"10","author":"RA Swanson","year":"1990","unstructured":"Swanson RA, Morton MT, Tsao-Wu G, Savalos RA, Davidson C, Sharp FR. A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab. 1990;10(2):290\u20133.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"4163_CR53","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1097\/00004647-200001000-00015","volume":"20","author":"M Sawada","year":"2000","unstructured":"Sawada M, Alkayed NJ, Goto S, Crain BJ, Traystman RJ, Shaivitz A, Nelson RJ, Hurn PD. Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse. J Cereb Blood Flow Metab. 2000;20(1):112\u20138.","journal-title":"J Cereb Blood Flow Metab"},{"key":"4163_CR54","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-123","volume":"7","author":"HJ Motulsky","year":"2006","unstructured":"Motulsky HJ, Brown RE. Detecting outliers when fitting data with nonlinear regression - a new method based on robust nonlinear regression and the false discovery rate. BMC Bioinform. 2006;7: 123.","journal-title":"BMC Bioinform"},{"issue":"1","key":"4163_CR55","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1089\/jam.2006.19.92","volume":"19","author":"L Illum","year":"2006","unstructured":"Illum L. Nasal clearance in health and disease. J Aerosol Med. 2006;19(1):92\u20139.","journal-title":"J Aerosol Med"},{"issue":"7","key":"4163_CR56","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1023\/A:1015830907632","volume":"8","author":"NG Schipper","year":"1991","unstructured":"Schipper NG, Verhoef JC, Merkus FW. The nasal mucociliary clearance: relevance to nasal drug delivery. Pharm Res. 1991;8(7):807\u201314.","journal-title":"Pharm Res"},{"key":"4163_CR57","volume":"11","author":"B Alwali","year":"2026","unstructured":"Alwali B, Parumasivam T, Al-Tabakha MM. Intranasal drug delivery: Unlocking the nose-to-brain route for central nervous system therapies. Int J Pharm X. 2026;11: 100521.","journal-title":"Int J Pharm X"},{"issue":"1","key":"4163_CR58","doi-asserted-by":"publisher","first-page":"10833","DOI":"10.1038\/s41598-020-67532-2","volume":"10","author":"TR Wood","year":"2020","unstructured":"Wood TR, Gundersen JK, Falck M, Maes E, Osredkar D, Loberg EM, Sabir H, Walloe L, Thoresen M. Variability and sex-dependence of hypothermic neuroprotection in a rat model of neonatal hypoxic-ischaemic brain injury: a single laboratory meta-analysis. Sci Rep. 2020;10(1):10833.","journal-title":"Sci Rep"},{"key":"4163_CR59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1243364","volume":"14","author":"LA Kelly","year":"2023","unstructured":"Kelly LA, Branagan A, Semova G, Molloy EJ. Sex differences in neonatal brain injury and inflammation. Front Immunol. 2023;14: 1243364.","journal-title":"Front Immunol"},{"key":"4163_CR60","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/867531","author":"CA Hill","year":"2012","unstructured":"Hill CA, Fitch RH. Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice. Neurol Res Int. 2012. https:\/\/doi.org\/10.1155\/2012\/867531.","journal-title":"Neurol Res Int"},{"key":"4163_CR61","doi-asserted-by":"publisher","first-page":"7 8 1","DOI":"10.1002\/cpph.9","volume":"74","author":"KM Knights","year":"2016","unstructured":"Knights KM, Stresser DM, Miners JO, Crespi CL. In vitro drug metabolism using liver microsomes. Curr Protoc Pharmacol. 2016;74:7 8 1-7 8 24.","journal-title":"Curr Protoc Pharmacol"},{"issue":"8","key":"4163_CR62","doi-asserted-by":"publisher","first-page":"822","DOI":"10.2174\/138920007782798207","volume":"8","author":"L Jia","year":"2007","unstructured":"Jia L, Liu X. The conduct of drug metabolism studies considered good practice (II): in vitro experiments. Curr Drug Metab. 2007;8(8):822\u20139.","journal-title":"Curr Drug Metab"},{"key":"4163_CR63","doi-asserted-by":"publisher","first-page":"17671","DOI":"10.1038\/srep17671","volume":"5","author":"H Zhang","year":"2015","unstructured":"Zhang H, Gao N, Tian X, Liu T, Fang Y, Zhou J, Wen Q, Xu B, Qi B, Gao J, Li H, Jia L, Qiao H. Content and activity of human liver microsomal protein and prediction of individual hepatic clearance in vivo. Sci Rep. 2015;5:17671.","journal-title":"Sci Rep"},{"issue":"6","key":"4163_CR64","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1208\/s12248-016-9962-6","volume":"18","author":"UA Argikar","year":"2016","unstructured":"Argikar UA, Potter PM, Hutzler JM, Marathe PH. Challenges and opportunities with non-CYP enzymes aldehyde oxidase, carboxylesterase, and UDP-glucuronosyltransferase: focus on reaction phenotyping and prediction of human clearance. AAPS J. 2016;18(6):1391\u2013405.","journal-title":"AAPS J"},{"issue":"9","key":"4163_CR65","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1517\/17425255.4.9.1153","volume":"4","author":"JM Hatfield","year":"2008","unstructured":"Hatfield JM, Wierdl M, Wadkins RM, Potter PM. Modifications of human carboxylesterase for improved prodrug activation. Expert Opin Drug Metab Toxicol. 2008;4(9):1153\u201365.","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"6","key":"4163_CR66","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1203\/pdr.0b013e31805341dc","volume":"61","author":"PA Statler","year":"2007","unstructured":"Statler PA, McPherson RJ, Bauer LA, Kellert BA, Juul SE. Pharmacokinetics of high-dose recombinant erythropoietin in plasma and brain of neonatal rats. Pediatr Res. 2007;61(6):671\u20135.","journal-title":"Pediatr Res"},{"key":"4163_CR67","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1016\/j.biopha.2018.11.041","volume":"109","author":"L Goenka","year":"2019","unstructured":"Goenka L, Uppugunduri Satyanarayana CR, S SK, George M. Neuroprotective agents in acute ischemic stroke-a reality check. Biomed Pharmacother. 2019;109:2539\u201347.","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"4163_CR68","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1542\/peds.2012-0498","volume":"130","author":"YW Wu","year":"2012","unstructured":"Wu YW, Bauer LA, Ballard RA, Ferriero DM, Glidden DV, Mayock DE, Chang T, Durand DJ, Song D, Bonifacio SL, Gonzalez FF, Glass HC, Juul SE. Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics. 2012;130(4):683\u201391.","journal-title":"Pediatrics"},{"key":"4163_CR69","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1508696","volume":"15","author":"SY Lim","year":"2024","unstructured":"Lim SY, Scarlett CO, Yapici S, Ferrazzano P, Cengiz P. Pharmacokinetics of 7,8-dihydroxyflavone in neonatal mice with hypoxia-ischemia related brain injury. Front Pharmacol. 2024;15: 1508696.","journal-title":"Front Pharmacol"},{"issue":"32","key":"4163_CR70","doi-asserted-by":"publisher","first-page":"3997","DOI":"10.2174\/1381612826666200421123242","volume":"26","author":"X Chen","year":"2020","unstructured":"Chen X, Song D, Nakada S, Qiu J, Iwamoto K, Chen RH, Lim YP, Jusko WJ, Stonestreet BS. Pharmacokinetics of inter-alpha inhibitor proteins and effects on hemostasis after hypoxic-ischemic brain injury in neonatal rats. Curr Pharm Des. 2020;26(32):3997\u20134006.","journal-title":"Curr Pharm Des"},{"key":"4163_CR71","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20123108","author":"R Abdul Razzak","year":"2019","unstructured":"Abdul Razzak R, Florence GJ, Gunn-Moore FJ. Approaches to CNS drug delivery with a focus on transporter-mediated transcytosis. Int J Mol Sci. 2019. https:\/\/doi.org\/10.3390\/ijms20123108.","journal-title":"Int J Mol Sci"},{"key":"4163_CR72","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmt.2022.101631","volume":"29","author":"ML Formica","year":"2022","unstructured":"Formica ML, Real DA, Picchio ML, Catlin E, Donnelly RF, Paredes AJ. On a highway to the brain: a review on nose-to-brain drug delivery using nanoparticles. Appl Mater Today. 2022;29: 101631.","journal-title":"Appl Mater Today"},{"key":"4163_CR73","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043390","author":"E Marcello","year":"2023","unstructured":"Marcello E, Chiono V. Biomaterials-enhanced intranasal delivery of drugs as a direct route for brain targeting. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms24043390.","journal-title":"Int J Mol Sci"},{"issue":"7","key":"4163_CR74","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jnr.24590","volume":"98","author":"C Disdier","year":"2020","unstructured":"Disdier C, Stonestreet BS. Hypoxic-ischemic-related cerebrovascular changes and potential therapeutic strategies in the neonatal brain. J Neurosci Res. 2020;98(7):1468\u201384.","journal-title":"J Neurosci Res"},{"key":"4163_CR75","doi-asserted-by":"crossref","unstructured":"Chauhan MB, Chauhan NB. Brain uptake of neurotherapeutics after Intranasal versus intraperitoneal delivery in mice. J Neurol Neurosurg. 2015;2(1).\u00a0https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26366437.","DOI":"10.19104\/jnn.2015.91"},{"issue":"1","key":"4163_CR76","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s40035-025-00481-w","volume":"14","author":"I Drath","year":"2025","unstructured":"Drath I, Richter F, Feja M. Nose-to-brain drug delivery: from bench to bedside. Transl Neurodegener. 2025;14(1):23.","journal-title":"Transl Neurodegener"},{"issue":"2","key":"4163_CR77","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3109\/10717544.2013.838713","volume":"21","author":"D Mittal","year":"2014","unstructured":"Mittal D, Ali A, Md S, Baboota S, Sahni JK, Ali J. Insights into direct nose to brain delivery: current status and future perspective. Drug Deliv. 2014;21(2):75\u201386.","journal-title":"Drug Deliv"},{"issue":"7","key":"4163_CR78","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s40263-022-00930-4","volume":"36","author":"A Lofts","year":"2022","unstructured":"Lofts A, Abu-Hijleh F, Rigg N, Mishra RK, Hoare T. Using the intranasal route to administer drugs to treat neurological and psychiatric illnesses: rationale, successes, and future needs. CNS Drugs. 2022;36(7):739\u201370.","journal-title":"CNS Drugs"},{"key":"4163_CR79","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14030588","author":"PC Pires","year":"2022","unstructured":"Pires PC, Rodrigues M, Alves G, Santos AO. Strategies to improve drug strength in nasal preparations for brain delivery of low aqueous solubility drugs. Pharmaceutics (Basel). 2022. https:\/\/doi.org\/10.3390\/pharmaceutics14030588.","journal-title":"Pharmaceutics (Basel)"},{"issue":"3","key":"4163_CR80","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1124\/jpet.119.258152","volume":"370","author":"Z Wang","year":"2019","unstructured":"Wang Z, Xiong G, Tsang WC, Sch\u00e4tzlein AG, Uchegbu IF. Nose-to-brain delivery. J Pharmacol Exp Ther. 2019;370(3):593\u2013601.","journal-title":"J Pharmacol Exp Ther"},{"key":"4163_CR81","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13111904","author":"F Maigler","year":"2021","unstructured":"Maigler F, Ladel S, Flamm J, Ganger S, Kurpiers B, Kiderlen S, Volk R, Hamp C, Hartung S, Spiegel S, Soleimanizadeh A, Eberle K, Hermann R, Krainer L, Pitzer C, Schindowski K. Selective CNS targeting and distribution with a refined region-specific intranasal delivery technique via the olfactory mucosa. Pharmaceutics. 2021. https:\/\/doi.org\/10.3390\/pharmaceutics13111904.","journal-title":"Pharmaceutics"},{"issue":"1","key":"4163_CR82","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-019-2745-x","volume":"37","author":"A Al Shoyaib","year":"2019","unstructured":"Al Shoyaib A, Archie SR, Karamyan VT. Intraperitoneal route of drug administration: should it be used in experimental animal studies? Pharm Res. 2019;37(1): 12.","journal-title":"Pharm Res"},{"key":"4163_CR83","doi-asserted-by":"crossref","unstructured":"Percie du Sert N, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, et al. Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol. 2020;18(7):e3000411.","DOI":"10.1371\/journal.pbio.3000411"},{"issue":"9","key":"4163_CR84","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1177\/0271678X20943823","volume":"40","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Wurbel H. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. J Cereb Blood Flow Metab. 2020;40(9):1769\u201377.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"6","key":"4163_CR85","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1177\/01926233231208987","volume":"51","author":"T Steger-Hartmann","year":"2023","unstructured":"Steger-Hartmann T, Clark M. Can historical control group data be used to replace concurrent controls in animal studies? Toxicol Pathol. 2023;51(6):361\u20132.","journal-title":"Toxicol Pathol"},{"issue":"2","key":"4163_CR86","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1097\/ALN.0000000000004258","volume":"137","author":"BL Li","year":"2022","unstructured":"Li BL, Guan YP, Yuen VM, Wei W, Huang M, Zhang MZ, Li AW, Standing JF, Zhong GP, Song XR. Population pharmacokinetics of intranasal dexmedetomidine in infants and young children. Anesthesiology. 2022;137(2):163\u201375.","journal-title":"Anesthesiology"},{"issue":"3","key":"4163_CR87","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1159\/000521949","volume":"119","author":"D Snyers","year":"2022","unstructured":"Snyers D, Tribolet S, Rigo V. Intranasal analgosedation for infants in the neonatal intensive care unit: a systematic review. Neonatology. 2022;119(3):273\u201384.","journal-title":"Neonatology"},{"issue":"3","key":"4163_CR88","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1080\/17425247.2025.2587185","volume":"23","author":"X Owen","year":"2026","unstructured":"Owen X, Hejazi M, Golshahi L. Navigating the challenges in pediatric intranasal drug delivery. Expert Opin Drug Deliv. 2026;23(3):449\u201366.","journal-title":"Expert Opin Drug Deliv"},{"issue":"5","key":"4163_CR89","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1002\/jps.2600800522","volume":"80","author":"S Gizurarson","year":"1991","unstructured":"Gizurarson S, Rasmussen SN, Larsen F. Pharmacokinetics of intranasal drug administration: the influence of some biological factors. J Pharm Sci. 1991;80(5):505\u20136.","journal-title":"J Pharm Sci"}],"container-title":["Pharmaceutical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-026-04163-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11095-026-04163-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-026-04163-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:02:48Z","timestamp":1791306168000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11095-026-04163-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":89,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["4163"],"URL":"https:\/\/doi.org\/10.1007\/s11095-026-04163-8","relation":{},"ISSN":["0724-8741","1573-904X"],"issn-type":[{"value":"0724-8741","type":"print"},{"value":"1573-904X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]},"assertion":[{"value":"12 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"No conflicts of interest, financial or otherwise, are declared by the authors.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}