Brain injury; Developing brain; hypoxia-ischemia; inflammation; magnetic resonance imaging; preterm infant; Lactoferrin
T. J. Ochoa, S. V. Sizonenko (2017), Lactoferrin and prematurity: a promising milk protein?, in Biochemestry and Cell Biology
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Vanessa Ginet, Yohan van de Looij, Volodymyr Petrenko, Audrey Toulotte, Jozsef Kiss, Petra S. Hüppi, Ste phane V Sizonenko (2016), Lactoferrin during lactation reduces lipopolysaccharide-induced brain injury, in Biofactors
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Van de Looij Yohan, Ginet Vanessa, Chatagner Alexandra, Toulotte Audrey, Huppi Petra, Sizonenko Stéphane (2014), Lactoferrin during lactation protects the immature hypoxic- ischemic rat brain, in Annals of Clinical and Translational Neurology
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Kunz Nicolas, Sizonenko Stéphane V., Huppi Petra S., Gruetter Rolf, van de Looij Yohan (2013), Investigation of field and diffusion time dependence of the diffusion-weighted signal at ultrahigh magnetic fields, in NMR in Biomedicine
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1.Research summaryPreterm infants are at high risk of brain injury that can lead to severe neurological disorders, cognitive deficits, delayed neurodevelopment and psychiatric diseases requiring special education and health needs with high human, social and economic costs.Hypoxia-Ischemia (HI) and inflammation (INF) are major triggers of preterm brain damage, with acute tissue injury and healing and with modification of the subsequent cerebral development and plasticity leading to a specific pattern of myelination deficit and grey matter loss. Despite similar pattern of resulting damage, the mechanisms of acute injury are different. Lactoferrin ß (LF) is an iron-binding glycoprotein, with roles in the iron uptake and homeostasis, in the regulation of immune response and it has antioxidant activities. Supplementation in pre-term infants appears to reduce sepsis and necrotising enterocolitis. High level is found in human milk. Secretion in colostrum, milk and transport from intestine to brain are highly regulated. LF binding sites are present in brain endothelial capillary cells and it is actively transported into the brain. A role of lactoferrin in brain development is suggested. Using a prenatal stress rat model by dexamethasone exposure during gestation, we have induced developmental alteration of brain structure, metabolism and function. Supplementation of dams during gestation and lactation with LF reverted most of these alterations possibly through the neurotrophic factors BDNF and NGF. Therefore, LF appears as a promising therapeutic interven-tion to protect the developing brain.We aim to study cerebral damage and repair after LF nutritional intervention in the developing brain using a multi-modal approach of high field in vivo magnetic resonance imaging, functional cortical somatosensory evoked potential and behaviour in neonatal rat models of cerebral HI and INF injuries. The potential of the combination of the in vivo techniques with detailed neuro-pathological assessment in HI and INF models will further delineate the effects of therapeutic intervention with LF.A protective action of LF on the developing brain in addition to the recently described protective effects on gut inflammation and systemic infection in the preterm infant, would give to this nutri-tional supplement a major role in neonatal therapies.