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Abstract
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.