U. Ådén, G. Favrais, F. Plaisant, M. Winerdal, U. Felderhoff-mueser et al., Systemic inflammation sensitizes the neonatal brain to excitotoxicity through a pro-/anti-inflammatory imbalance: key role of TNF? pathway and protection by etanercept, Brain Behav Immun, vol.24, pp.747-758, 2010.

M. V. Avshalumov, B. T. Chen, S. P. Marshall, D. M. Peña, and M. E. Rice, Glutamate-dependent inhibition of dopamine release in striatum is mediated by a new diffusible messenger, H2O2, J Neurosci, vol.23, pp.2744-2750, 2003.

A. Ayala, M. F. Muñoz, and S. Argüelles, Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal, Oxid Med Cell Longev, vol.360438, 2014.

S. A. Back, White matter injury in the preterm infant: pathology and mechanisms, Acta Neuropathol, vol.134, pp.331-349, 2017.

O. Baud, A. E. Greene, J. Li, H. Wang, J. J. Volpe et al., Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes, J Neurosci, vol.24, pp.1531-1540, 2004.

G. P. Bienert and F. Chaumont, Aquaporin-facilitated transmembrane diffusion of hydrogen peroxide, Biochim Biophys Acta, vol.1840, pp.1596-1604, 2014.

G. P. Bienert, J. K. Schjoerring, and T. P. Jahn, Membrane transport of hydrogen peroxide, Biochim Biophys Acta, vol.1758, pp.994-1003, 2006.

R. Brigelius-flohé and M. Maiorino, Glutathione peroxidases, Biochim Biophys Acta, vol.1830, pp.3289-3303, 2013.

G. Buonocore, S. Perrone, and R. Bracci, Free radicals and brain damage in the newborn, Biol Neonate, vol.79, pp.180-186, 2001.

J. D. Carver, V. J. Benford, B. Han, and A. B. Cantor, The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects, Brain Res Bull, vol.56, pp.551-553, 2001.

W. H. Cheng, Y. S. Ho, B. A. Valentine, D. A. Ross, G. F. Combs et al., Cellular glutathione peroxidase is the mediator of body selenium to protect against paraquat lethality in transgenic mice, J Nutr, vol.128, pp.1070-1076, 1998.

E. M. Cornford, J. B. Varesi, S. Hyman, R. T. Damian, and M. J. Raleigh, Mitochondrial content of choroid plexus epithelium, Exp Brain Res, vol.116, pp.399-405, 1997.

R. Daneman, L. Zhou, A. A. Kebede, and B. A. Barres, Pericytes are required for blood-brain barrier integrity during embryogenesis, Nature, vol.468, pp.562-566, 2010.

S. Desagher, J. Glowinski, and J. Premont, Astrocytes protect neurons from hydrogen peroxide toxicity, J Neurosci, vol.16, pp.2553-2562, 1996.

R. Dringen, M. Brandmann, M. C. Hohnholt, and E. M. Blumrich, Glutathionedependent detoxification processes in astrocytes, Neurochem Res, vol.40, pp.2570-2582, 2015.

R. Dringen and B. Hamprecht, Involvement of glutathione peroxidase and catalase in the disposal of exogenous hydrogen peroxide by cultured astroglial cells, Brain Res, vol.759, pp.233-236, 1997.

R. Dringen, L. Kussmaul, and B. Hamprecht, Detoxification of exogenous hydrogen peroxide and organic hydroperoxides by cultured astroglial cells assessed by microtiter plate assay, Brain Res Brain Res Protoc, vol.2, pp.223-228, 1998.

K. M. Dziegielewska, J. Ek, M. D. Habgood, and N. R. Saunders, Development of the choroid plexus, Microsc Res Tech, vol.52, pp.5-20, 2001.

H. J. Forman, A. Bernardo, and K. Davies, What is the concentration of hydrogen peroxide in blood and plasma?, Arch Biochem Biophys, vol.603, issue.7, pp.48-53, 2016.

C. Gauron, F. Meda, E. Dupont, S. Albadri, N. Quenech'du et al., The cyclopentenone product of lipid peroxidation, 15-A(2t)-isoprostane (8-isoprostaglandin A(2)), is efficiently conjugated with glutathione by human and rat glutathione transferase A4 -4, References Baxter PS, Hardingham GE (2016) Adaptive regulation of the brain's antioxidant defences by neurons and astrocytes, vol.414, pp.17553-17559, 1970.

R. Lin, J. Cai, C. Nathan, X. Wei, S. Schleidt et al., Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistance. kinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity, Neurogenesis is enhanced by stroke in multiple new stem cell niches along the ventricular system at sites of high BBB permeability, vol.74, pp.6275-6289, 1990.

N. Strazielle, J. Ghersi-egea, N. Strazielle, and J. F. Ghersi-egea, Choroid plexus controls brain availability of anti-HIV nucleoside analogs via pharmacologically inhibitable organic anion transporters, Physiology of blood-brain interfaces in relation to brain disposition of small compounds and macromolecules, vol.10, pp.1717-1740, 2003.

R. M. Smyth, E. Gargon, J. Kirkham, L. Cresswell, S. Golder et al., Adverse drug reactions in children-a systematic review, PLoS One, vol.7, issue.3, p.24061, 2012.

J. R. Bellis, J. J. Kirkham, S. Thiesen, E. J. Conroy, L. E. Bracken et al., Adverse drug reactions and off-label and unlicensed medicines in children: a nested case-control study of inpatients in a pediatric hospital, BMC Med, vol.11, p.238, 2013.

E. M. Agency, Evidence of harm from off-label or unlicensed medicines in children, 2004.

A. A. Elzagallaai, M. Greff, and M. J. Rieder, Adverse drug reactions in children: the double-edged sword of therapeutics, Clin Pharmacol Ther, vol.101, issue.6, pp.725-760, 2017.

C. Ko, H. Sammons, and I. Choonara, Systematic review of paediatric studies of adverse drug reactions from pharmacovigilance databases, Expert Opin Drug Saf, vol.15, issue.10, pp.1321-1329, 2016.

D. B. Andropoulos, Effect of anesthesia on the developing brain: infant and fetus, Fetal Diagn Ther, vol.43, issue.1, pp.1-11, 2018.

K. K. Jain, Drug-induced neurological disorders, 2011.

U. Hanke, K. May, V. Rozehnal, S. Nagel, W. Siegmund et al., Commonly used nonionic surfactants interact differently with the human efflux transporters ABCB1 (p-glycoprotein) and ABCC2 (MRP2), Eur J Pharm Biopharm, vol.76, issue.2, pp.260-268, 2010.

E. M. Agency, Reflection paper on extrapolation of efficacy and safety in 4 paediatric medicine development, 2016.

, Pediatric Science and Research Activities

E. M. Agency, Needs for paediatric medicines

R. M. Ward, D. K. Benjamin, J. Davis, J. M. Gorman, R. L. Kauffman et al., The need for pediatric drug development, J Pediatr, 2017.

A. Rai, S. Bhalla, S. S. Rebello, H. Kastrissios, and A. Gulati, Disposition of morphine in plasma and cerebrospinal fluid varies during neonatal development in pigs, J Pharm Pharmacol, vol.57, issue.8, pp.981-987, 2005.

M. Hausler, C. Schafer, C. Osterwinter, and W. Jahnen-dechent, The physiologic development of fetuin-a serum concentrations in children, Pediatr Res, vol.66, issue.6, pp.660-664, 2009.

M. Ehrnebo, S. Agurell, B. Jalling, and L. O. Boreus, Age differences in drug binding by plasma proteins: studies on human foetuses, neonates and adults, Eur J Clin Pharmacol, vol.3, issue.4, pp.189-93, 1971.

H. M. Sammons and I. Choonara, Learning lessons from adverse drug reactions in children, Children (Basel), vol.3, issue.1, p.1, 2016.

B. Thyagarajan and S. S. Deshpande, Cotrimoxazole and neonatal kernicterus: a review, Drug Chem Toxicol, vol.37, issue.2, pp.121-130, 2014.

N. Strazielle and J. F. Ghersi-egea, Physiology of blood-brain interfaces in relation to brain disposition of small compounds and macromolecules, Mol Pharm, vol.10, issue.5, pp.1473-91, 2013.

A. D. Workman, C. J. Charvet, B. Clancy, R. B. Darlington, and B. L. Finlay, Modeling transformations of neurodevelopmental sequences across mammalian species, J Neurosci, vol.33, issue.17, pp.7368-83, 2013.

J. D. Fenstermacher, Implications of the blood-brain barrier and its manipulation, pp.137-55, 1989.

J. Westerhout, M. Danhof, D. Lange, and E. C. , Preclinical prediction of human brain target site concentrations: considerations in extrapolating to the clinical setting, J Pharm Sci, vol.100, issue.9, pp.3577-93, 2011.

A. Nehlig, A. Pereira-de-vasconcelos, and S. Boyet, Postnatal changes in local cerebral blood flow measured by the quantitative autoradiographic [14C]iodoantipyrine technique in freely moving rats, J Cereb Blood Flow Metab, vol.9, issue.5, pp.579-88, 1989.

L. Wei, T. Otsuka, V. Acuff, D. Bereczki, K. Pettigrew et al., The velocities of red cell and plasma flows through parenchymal microvessels of rat brain are decreased by pentobarbital, J Cereb Blood Flow Metab, vol.13, issue.3, pp.487-97, 1993.

N. Strazielle and J. F. Ghersi-egea, Choroid plexus in the central nervous system: biology and physiopathology, J Neuropathol Exp Neurol, vol.59, issue.7, pp.561-74, 2000.

D. W. Caley and D. S. Maxwell, Development of the blood vessels and extracellular spaces during postnatal maturation of rat cerebral cortex, J Comp Neurol, vol.138, issue.1, pp.31-47, 1970.

K. M. Dziegielewska, J. Ek, M. D. Habgood, and N. R. Saunders, Development of the choroid plexus, Microsc Res Tech, vol.52, issue.1, pp.5-20, 2001.

J. Szmydynger-chodobska, A. Chodobski, and C. E. Johanson, Postnatal developmental changes in blood flow to choroid plexuses and cerebral cortex of the rat, Am J Phys, vol.266, issue.5, pp.1488-92, 1994.

M. Hammarlund-udenaes, M. Friden, S. Syvanen, and A. Gupta, On the rate and extent of drug delivery to the brain, Pharm Res, vol.25, issue.8, pp.1737-50, 2008.

R. Daneman, L. Zhou, A. A. Kebede, and B. A. Barres, Pericytes are required for blood-brain barrier integrity during embryogenesis, Nature, vol.468, issue.7323, pp.562-568, 2010.

A. Lehmenkuhler, E. Sykova, J. Svoboda, K. Zilles, and C. Nicholson, Extracellular space parameters in the rat neocortex and subcortical white matter during postnatal development determined by diffusion analysis, Neuroscience, vol.55, issue.2, pp.339-51, 1993.

S. Yang, Y. Wang, K. Li, X. Tang, K. Zhang et al., Extracellular space diffusion analysis in the infant and adult rat striatum using magnetic resonance imaging, Int J Dev Neurosci, vol.53, pp.1-7, 2016.

J. F. Ghersi-egea, W. Finnegan, J. L. Chen, and J. D. Fenstermacher, Rapid distribution of intraventricularly administered sucrose into cerebrospinal fluid cisterns via subarachnoid velae in rat, Neuroscience, vol.75, issue.4, pp.1271-88, 1996.

P. M. Knopf, H. F. Cserr, S. C. Nolan, T. Y. Wu, and C. J. Harling-berg, Physiology and immunology of lymphatic drainage of interstitial and cerebrospinal fluid from the brain, Neuropathol Appl Neurobiol, vol.21, issue.3, pp.175-80, 1995.

J. F. Ghersi-egea, A. Babikian, S. Blondel, and N. Strazielle, Changes in the cerebrospinal fluid circulatory system of the developing rat: quantitative volumetric analysis and effect on blood-CSF permeability interpretation, Fluids Barriers CNS, vol.12, p.8, 2015.
URL : https://hal.archives-ouvertes.fr/inserm-01264513

N. H. Bass and P. Lundborg, Postnatal development of bulk flow in the cerebrospinal fluid system of the albino rat: clearance of carboxyl-( 14 C)inulin after intrathecal infusion, Brain Res, vol.52, pp.323-355, 1973.

H. C. Jones, R. Deane, and R. M. Bucknall, Developmental changes in cerebrospinal fluid pressure and resistance to absorption in rats, Dev Brain Res, vol.33, issue.1, pp.23-30, 1987.

C. E. Johanson, J. A. Duncan, P. M. Klinge, T. Brinker, E. G. Stopa et al., Multiplicity of cerebrospinal fluid functions: new challenges in health and disease, Cerebrospinal Fluid Res, vol.5, p.10, 2008.

K. M. Dziegielewska, C. A. Evans, D. H. Malinowska, K. Mollgard, J. M. Reynolds et al., Studies of the development of brain barrier systems to lipid insoluble molecules in fetal sheep, J Physiol, vol.292, pp.207-238, 1979.

N. R. Saunders, G. W. Knott, and K. M. Dziegielewska, Barriers in the immature brain, Cell Mol Neurobiol, vol.20, issue.1, pp.29-40, 2000.

D. Dickens, S. D. Webb, S. Antonyuk, A. Giannoudis, A. Owen et al., , p.1

, Biochem Pharmacol, vol.85, issue.11, pp.1672-83, 2013.

N. Y. Lee, H. O. Choi, and Y. S. Kang, The acetylcholinesterase inhibitors competitively inhibited an acetyl L-carnitine transport through the blood-brain barrier, Neurochem Res, vol.37, issue.7, pp.1499-507, 2012.

P. Vlieghe and M. Khrestchatisky, Medicinal chemistry based approaches and nanotechnology-based systems to improve CNS drug targeting and delivery, Med Res Rev, vol.33, issue.3, pp.457-516, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01718195

K. Goasdoue, S. M. Miller, P. B. Colditz, and S. T. Bjorkman, Review: the blood-brain barrier; protecting the developing fetal brain, Placenta, vol.54, pp.111-117, 2017.

N. Strazielle, S. T. Khuth, and J. F. Ghersi-egea, Detoxification systems, passive and specific transport for drugs at the blood-CSF barrier in normal and pathological situations, Adv Drug Deliv Rev, vol.56, issue.12, pp.1717-1757, 2004.

F. Schlachetzki, C. Zhu, and W. M. Pardridge, Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier, J Neurochem, vol.81, issue.1, pp.203-209, 2002.

K. Mollgard, K. M. Dziegielewska, C. B. Holst, M. D. Habgood, and N. R. Saunders, Brain barriers and functional interfaces with sequential appearance of ABC efflux transporters during human development, Sci Rep, vol.7, issue.1, p.11603, 2017.

I. Kratzer, A. Vasiljevic, C. Rey, M. Fevre-montange, N. Saunders et al., Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier, Histochem Cell Biol, vol.138, issue.6, pp.861-79, 2012.

S. A. Liddelow, K. M. Dziegielewska, C. J. Ek, M. D. Habgood, H. Bauer et al., Mechanisms that determine the internal environment of the developing brain: a transcriptomic, functional and ultrastructural approach, PLoS One, vol.8, issue.7, p.65629, 2013.

C. J. Ek, K. M. Dziegielewska, H. Stolp, and N. R. Saunders, Functional effectiveness of the blood-brain barrier to small water-soluble molecules in developing and adult opossum (Monodelphis domestica), J Comp Neurol, vol.496, issue.1, pp.13-26, 2006.

A. Armulik, G. Genove, M. Mae, M. H. Nisancioglu, E. Wallgard et al., Pericytes regulate the blood-brain barrier, Nature, vol.468, issue.7323, pp.557-61, 2010.

M. S. Conrad and R. W. Johnson, The domestic piglet: an important model for investigating the neurodevelopmental consequences of early life insults, Annu Rev Anim Biosci, vol.3, pp.245-64, 2015.

B. S. Stonestreet, G. H. Burgess, and H. F. Cserr, Blood-brain barrier integrity and brain water and electrolytes during hypoxia/hypercapnia and hypotension in newborn piglets, Brain Res, vol.590, issue.1-2, pp.263-70, 1992.

R. L. Leino, D. Z. Gerhart, and L. R. Drewes, Monocarboxylate transporter (MCT1) abundance in brains of suckling and adult rats: a quantitative electron microscopic immunogold study, Brain Res Dev Brain Res, vol.113, issue.1-2, pp.47-54, 1999.

N. Strazielle and J. F. Ghersi-egea, Efflux transporters in blood-brain interfaces of the developing brain, Front Neurosci, vol.9, p.21, 2015.

S. Gazzin, N. Strazielle, C. Schmitt, M. Fevre-montange, J. D. Ostrow et al., Differential expression of the multidrug resistancerelated proteins ABCb1 and ABCc1 between blood-brain interfaces, J Comp Neurol, vol.510, issue.5, pp.497-507, 2008.

S. Baello, M. Iqbal, W. Gibb, and S. G. Matthews, Astrocyte-mediated regulation of multidrug resistance p-glycoprotein in fetal and neonatal brain endothelial cells: age-dependent effects, Phys Rep, vol.4, issue.16, p.12853, 2016.

N. R. Saunders, K. M. Dziegielewska, K. Mollgard, M. D. Habgood, M. J. Wakefield et al., Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study, Front Neurosci, vol.9, p.123, 2015.

R. Shawahna, Y. Uchida, X. Decleves, S. Ohtsuki, S. Yousif et al., Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels, Mol Pharm, vol.8, issue.4, pp.1332-1373, 2011.

I. Kratzer, S. A. Liddelow, N. R. Saunders, K. M. Dziegielewska, N. Strazielle et al., Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection, Fluids Barriers CNS, vol.10, issue.1, p.25, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00850664

D. Virgintino, D. Robertson, V. Benagiano, M. Errede, M. Bertossi et al., Immunogold cytochemistry of the blood-brain barrier glucose transporter GLUT1 and endogenous albumin in the developing human brain, Brain Res Dev Brain Res, vol.123, issue.1, pp.95-101, 2000.

N. Strazielle and J. F. Ghersi-egea, Potential pathways for CNS drug delivery across the blood-cerebrospinal fluid barrier, Curr Pharm Des, vol.22, issue.35, pp.5463-76, 2016.

R. Moretti, J. Pansiot, D. Bettati, N. Strazielle, J. F. Ghersi-egea et al., Blood-brain barrier dysfunction in disorders of the developing brain, Front Neurosci, vol.9, p.40, 2015.

H. B. Stolp, K. M. Dziegielewska, C. J. Ek, M. D. Habgood, M. A. Lane et al., Breakdown of the blood-brain barrier to proteins in white matter of the developing brain following systemic inflammation, Cell Tissue Res, vol.320, issue.3, pp.369-78, 2005.

L. C. Hutton, M. Castillo-melendez, and D. W. Walker, Uteroplacental inflammation results in blood brain barrier breakdown, increased activated caspase 3 and lipid peroxidation in the late gestation ovine fetal cerebellum, Dev Neurosci, vol.29, issue.4-5, pp.341-54, 2007.

I. Kratzer, S. Chip, and Z. S. Vexler, Barrier mechanisms in neonatal stroke, Front Neurosci, vol.8, p.359, 2014.

K. Muramatsu, A. Fukuda, H. Togari, Y. Wada, and H. Nishino, Vulnerability to cerebral hypoxic-ischemic insult in neonatal but not in adult rats is in parallel with disruption of the blood-brain barrier, Stroke, vol.28, issue.11, pp.2281-2289, 1997.

D. Fernandez-lopez, F. J. Daneman, R. Zhou, L. Lee, S. Y. Derugin et al., Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat, J Neurosci, vol.32, issue.28, pp.9588-600, 2012.

S. Gazzin, A. L. Berengeno, N. Strazielle, F. Fazzari, A. Raseni et al., Modulation of Mrp1 (ABCc1) and Pgp (ABCb1) by bilirubin at the blood-CSF and blood-brain barriers in the Gunn rat, PLoS One, vol.6, issue.1, p.16165, 2011.

W. Neuhaus, M. Schlundt, M. Fehrholz, A. Ehrke, S. Kunzmann et al., Multiple antenatal dexamethasone treatment alters brain vessel differentiation in newborn mouse pups, PLoS One, vol.10, issue.8, p.136221, 2015.

M. Iqbal, S. Baello, M. Javam, M. C. Audette, W. Gibb et al., Regulation of multidrug resistance P-glycoprotein in the developing blood-brain barrier: interplay between glucocorticoids and cytokines, J Neuroendocrinol, vol.28, issue.3, p.12360, 2016.

J. F. Ghersi-egea, S. Gazzin, and N. Strazielle, Blood-brain interfaces and bilirubin-induced neurological diseases, Curr Pharm Des, vol.15, issue.25, pp.2893-907, 2009.