Lactoferrin during lactation reduces lipopolysaccharide-induced brain injury.
Lactoferrin (Lf), component of maternal milk, has antioxidant, anti-inflammatory and antimicrobial properties. Neuroprotective effects of Lf on the immature brain have been recently shown in rodent models of intrauterine growth restriction and cerebral hypoxia/ischemia. Here we postulated that Lf could also have beneficial effects on preterm inflammatory brain injury. Lf was supplemented in maternal food during lactation and lipopolysaccharide (LPS) was injected in subcortical white matter of rat pups at postnatal day 3 (P3). Effect of maternal Lf supplementation was investigated 24 h (P4), 4 (P7), or 21 days (P24) after LPS injection mainly on the striatum. Lateral ventricle and brain structures volumes were quantified. Microstructure was evaluated by diffusion tensor imaging, neurite orientation dispersion and density imaging as well as electron microscopy. Neurochemical profile was measured by (1) H-magnetic resonance spectroscopy. GFAP protein, proinflammatory cytokines mRNA expression microglial activation were assessed. Lf displayed neuroprotective effects as shown by reduced LPS-induced ventriculomegaly, brain tissue loss, and microstructural modifications, including myelination deficit. (1) H-MRS neurochemical profile was less altered through an antioxidant action of Lf. Despite the lack of effect on LPS-induced proinflammatory cytokines genes expression and on reactive gliosis, microglia was less activated under Lf treatment. In conclusion, Lf supplemented in food during lactation attenuated acute and long-term cerebral LPS-induced alterations. This provides a new evidence for a promising use of Lf as a preventive neuroprotective approach in preterm encephalopathy. © 2016 BioFactors, 42(3):323-336, 2016.
Division of Child Development and Growth, Department of Pediatrics, University of Geneva, Geneva, Switzerland.
Vanessa
V
Ginet
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.
Yohan
Y
van de Looij
Department of Fundamental Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Volodymyr
V
Petrenko
Division of Child Development and Growth, Department of Pediatrics, University of Geneva, Geneva, Switzerland.
Audrey
A
Toulotte
Department of Fundamental Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Jozsef
J
Kiss
Division of Child Development and Growth, Department of Pediatrics, University of Geneva, Geneva, Switzerland.
Petra S
PS
Hüppi
Division of Child Development and Growth, Department of Pediatrics, University of Geneva, Geneva, Switzerland.
Stéphane V
SV
Sizonenko
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001930:Brain Injuries / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology; D001931:Brain Mapping; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology; D007774:Lactation / Q000378:metabolism; D007781:Lactoferrin / Q000008:administration & dosage* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008892:Milk / Q000737:chemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats
D000975:Antioxidants; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D007781:Lactoferrin
electron microscopy; lactoferrin; lipopolysaccharide; magnetic resonance spectroscopy and imaging; perinatal brain