title: Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain.
abstract: OBJECTIVE
  Lactoferrin (Lf) is an iron-binding glycoprotein secreted in maternal milk presenting anti-inflammatory and antioxidant properties. It shows efficient absorption into the brain from nutritional source. Brain injury frequently resulting from cerebral hypoxia-ischemia (HI) has a high incidence in premature infants with ensuing neurodevelopmental disabilities. We investigated the neuroprotective effect of maternal nutritional supplementation with Lf during lactation in a rat model of preterm HI brain injury using magnetic resonance imaging (MRI), brain gene, and protein expression.
  
  
  METHODS
  Moderate brain HI was induced using unilateral common carotid artery occlusion combined with hypoxia (6%, 30 min) in the postnatal day 3 (P3) rat brain (24-28 weeks human equivalent). High-field multimodal MRI techniques were used to investigate the effect of maternal Lf supplementation through lactation. Expression of cytokine coding genes (TNF-α and IL-6), the prosurvival/antiapoptotic AKT protein and caspase-3 activation were also analyzed in the acute phase after HI.
  
  
  RESULTS
  MRI analysis demonstrated reduced cortical injury in Lf rats few hours post-HI and in long-term outcome (P25). Lf reduced HI-induced modifications of the cortical metabolism and altered white matter microstructure was recovered in Lf-supplemented rats at P25. Lf supplementation significantly decreased brain TNF-α and IL-6 gene transcription, increased phosphorylated AKT levels and reduced activation of caspase-3 at 24 h post-injury.
  
  
  CONCLUSIONS
  Lf given through lactation to rat pups with cerebral HI injury shows neuroprotective effects on brain metabolism, and cerebral gray and white matter recovery. This nutritional intervention may be of high interest for the clinical field of preterm brain neuroprotection.
authors.affiliation: Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland ; Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL) Lausanne, Switzerland.
authors.forename: Yohan
authors.initials: Y
authors.lastname: van de Looij
authors.affiliation: Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ginet
authors.affiliation: Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chatagner
authors.affiliation: Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
authors.forename: Audrey
authors.initials: A
authors.lastname: Toulotte
authors.affiliation: Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Somm
authors.affiliation: Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
authors.forename: Petra S
authors.initials: PS
authors.lastname: Hüppi
authors.affiliation: Division of Child Development and Growth, Department of Pediatrics, University of Geneva Geneva, Switzerland.
authors.forename: Stéphane V
authors.initials: SV
authors.lastname: Sizonenko