Based on the epidemiological association between maternal infection during pregnancy and enhanced risk of neurodevelopmental brain disorders in the offspring, a number of in-vivo models have been established in rats and mice in order to study this link on an experimental basis. These models provide indispensable experimental tools to test the hypothesis of causality in human epidemiological associations, and to explore the critical neuroimmunological and developmental factors involved in shaping the vulnerability to infection-induced neurodevelopmental disturbances in humans. Here, we summarize the findings derived from numerous in-vivo models of prenatal infection and/or immune activation in rats and mice, including models of exposure to influenza virus, bacterial endotoxin, viral-like acute phase responses and specific pro-inflammatory cytokines. Furthermore, we discuss the methodological aspects of these models in relation to their practical implementation and their translatability to the human condition. We highlight that these models can successfully examine the influence of the precise timing of maternal immune activation, the role of pro- and anti-inflammatory cytokines, and the contribution of gene-environment interactions in the association between prenatal immune challenge and postnatal brain dysfunctions. Finally, we discuss that in-vivo models of prenatal immune activation offer a unique opportunity to establish and evaluate early preventive interventions aiming to reduce the risk of long-lasting brain dysfunctions following prenatal exposure to infection.
Bibliographical noteFunding Information:
The studies performed at the authors’ institute were supported by the Swiss Federal Institute of Technology (ETH) Zurich (grant – 11 07/03; to UM and JF), the Swiss National Science Foundation (grant 310000-118284/1; to UM and JF), and the National Institute of Child Health and Human Development (grant #1R01 HD046589-01A2; to SHF). JF received additional support from a 2009 NARSAD Distinguished Investigator Award. We are extremely grateful to Dr. Andrea Engler for running the cytokine assays ( Fig. 3 ), and to Stéphanie Vuillermot for providing the photographs ( Fig. 1 ).
- Animal model
- Immune system