title: NF-κB activity in perinatal brain during infectious and hypoxic-ischemic insults revealed by a reporter mouse.
abstract: Infants suffering from infection or hypoxia-ischemia around the time of birth can develop brain damage resulting in life-long impairment such as cerebral palsy, epilepsy and cognitive disability. Inflammation appears to be an important contributor irrespective of whether the primary event is infection or hypoxia-ischemia. Activation of the transcription factor NF-κB is a hallmark of inflammation. To study perinatal brain inflammation, we developed a transgenic reporter mouse for imaging NF-κB activity in live animals and tissue samples. The reporter genes firefly luciferase and a destabilized version of enhanced GFP (dEGFP) were regulated by common NF-κB sites using a bidirectional promoter. Luciferase activity was imaged in vivo, while dEGFP was detected at cellular level in tissue sections. In newborn mice subjected to experimental models of infections or hypoxia-ischemia; luciferase signal increased in brains of live animals. In brain sections dEGFP expression, revealing NF-κB activation was observed in the endothelial cells of the blood-brain barrier in all disease models. In meningitis and hypoxia-ischemia expression of dEGFP was also induced in perivascular astrocytes. In conclusion, by using this transgenic reporter mouse in experimental models of perinatal complications, we could assess NF-κB activity in vivo and subsequently determine the cellular origin in the tissues.
authors: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors: Anders
authors: A
authors: Kielland
authors: Laura M A
authors: LM
authors: Camassa
authors: Gaute
authors: G
authors: Døhlen
authors: Ludvig A
authors: LA
authors: Munthe
authors: Rune
authors: R
authors: Blomhoff
authors: Mahmood
authors: M
authors: Amiry-Moghaddam
authors: Harald
authors: H
authors: Carlsen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism; D016920:Meningitis, Bacterial / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D049452:Green Fluorescent Proteins