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Updated: May 27, 2026
Methods for the Modulation and Analysis of NF-κB-dependent Adult Neurogenesis
Published on: February 13, 2014
NF-κB activity in perinatal brain during infectious and hypoxic-ischemic insults revealed by a reporter mouse
Anders Kielland1, Laura M A Camassa, Gaute Døhlen
1Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway.
Insights
Newborn brain inflammation, a cause of lifelong impairment, was studied using a novel reporter mouse. This tool visualizes nuclear factor-kappa B (NF-κB) activation in vivo, revealing its role in perinatal brain injury models.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Perinatal brain damage in infants, linked to infection or hypoxia-ischemia, causes lifelong impairments like cerebral palsy and cognitive disability.
- Inflammation is a key contributor to perinatal brain damage, regardless of the initial cause.
- Activation of the transcription factor nuclear factor-kappa B (NF-κB) is a central marker of inflammation.
Purpose of the Study:
- To develop and utilize a transgenic reporter mouse for real-time imaging of NF-κB activity in the developing brain.
- To investigate the role of NF-κB activation in experimental models of perinatal infection and hypoxia-ischemia.
- To identify the specific cell types involved in NF-κB activation during perinatal brain injury.
Main Methods:
- Development of a bidirectional transgenic reporter mouse with firefly luciferase and destabilized enhanced green fluorescent protein (dEGFP) under NF-κB control.
- In vivo imaging of luciferase activity to monitor NF-κB activation in live newborn mice.
- Ex vivo cellular-level detection of dEGFP expression in brain tissue sections to pinpoint NF-κB activation sites.
Main Results:
- Increased luciferase signal in the brains of live mice subjected to infection or hypoxia-ischemia models, indicating elevated NF-κB activity.
- dEGFP expression in brain sections confirmed NF-κB activation in endothelial cells of the blood-brain barrier across all disease models.
- NF-κB activation was also observed in perivascular astrocytes in meningitis and hypoxia-ischemia models.
Conclusions:
- The developed transgenic reporter mouse enables in vivo assessment of NF-κB activity during perinatal complications.
- This tool allows for the precise determination of the cellular origins of inflammation in the brain.
- Findings highlight the critical role of NF-κB in the inflammatory response to perinatal brain injury, offering potential therapeutic targets.
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.
