title: The role of different strain backgrounds in bacterial endotoxin-mediated sensitization to neonatal hypoxic-ischemic brain damage.
abstract: Genetic background is known to influence the outcome in mouse models of human disease, and previous experimental studies have shown strain variability in the neonatal mouse model of hypoxia-ischemia. To further map out this variability, we compared five commonly used mouse strains: C57BL/6, 129SVJ, BALB/c, CD1 and FVB in a pure hypoxic-ischemic setup and following pre-sensitization with lipopolysaccharide (LPS). Postnatal day 7 pups were subjected to unilateral carotid artery occlusion followed by continuous 30 min 8% oxygen exposure at 36 °C. Twelve hours prior, a third of the pups received a single intraperitoneal LPS (0.6 μg/g) or a saline (vehicle) administration, respectively; a further third underwent hypoxia-ischemia alone without preceding injection. Both C57BL/6 and 129SVJ strains showed minimal response to 30min hypoxia-ischemia alone, BALB/c demonstrated a moderate response, and both CD1 and FVB revealed the highest brain damage. LPS pre-sensitization led to substantial increase in overall brain infarction, microglial and astrocyte response and cell death in four of the five strains, with exception of BALB/c that only showed a significant effect with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Saline administration prior to hypoxia-ischemia resulted in an increase in inflammatory-associated markers, particularly in the astroglial activation of C57BL/6 mice, and in combined microglial activation and neuronal cell loss in FVB mice. Finally, two of the four strongly affected strains--C57BL/6 and CD1--revealed pronounced contralateral astrogliosis with a neuroanatomical localization similar to that observed on the occluded hemisphere. Overall, the current findings demonstrate strain differences in response to hypoxia-ischemia alone, to stress associated with vehicle injection, and to LPS-mediated pre-sensitization, which partially explains the high variability seen in the neonatal mouse models of hypoxia-ischemia. These results can be useful in future studies of fetal/neonatal response to inflammation and reduced oxygen-blood supply.
authors.affiliation: Perinatal Brain Protection and Repair Group, EGA Institute for Women's Health, University College London, WC1E 6HX London, UK. Electronic address: e.ferreira@ucl.ac.uk.
authors.forename: E
authors.initials: E
authors.lastname: Rocha-Ferreira
authors.affiliation: Perinatal Brain Protection and Repair Group, EGA Institute for Women's Health, University College London, WC1E 6HX London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Phillips
authors.affiliation: Perinatal Brain Protection and Repair Group, EGA Institute for Women's Health, University College London, WC1E 6HX London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Francesch-Domenech
authors.affiliation: Perinatal Brain Protection and Repair Group, EGA Institute for Women's Health, University College London, WC1E 6HX London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Thei
authors.affiliation: Perinatal Brain Protection and Repair Group, EGA Institute for Women's Health, University College London, WC1E 6HX London, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Peebles
authors.affiliation: Perinatal Brain Protection and Repair Group, EGA Institute for Women's Health, University College London, WC1E 6HX London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Raivich
authors.affiliation: Perinatal Brain Protection and Repair Group, EGA Institute for Women's Health, University College London, WC1E 6HX London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hristova
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002340:Carotid Artery Diseases; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology*; D008070:Lipopolysaccharides; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013045:Species Specificity
chemical_list: D008070:Lipopolysaccharides
keywords: 129SVJ; BALB/c; C57BL/6; CD1; FVB; hypoxia–ischemia