Does prenatal immune challenge result in increased extra-axial CSF volume?

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Abstract Enlarged extra-axial cerebrospinal fluid volume (CSF in the subarachnoid space) is an encouraging neuroimaging biomarker for the early detection of neurodevelopmental disorders (NDDs), particularly for autism spectrum disorder. The link between extra-axial CSF accumulation and NDDs is not yet fully clear. We propose that maternal immune activation (MIA) can help to inform about this question. Clinical and animal studies implicate MIA during the gestational period as a significant etiological cause of NDDs. MIA is associated with increases in maternal proinflammatory cytokines, and some of these cytokines can cross the placenta and reach the fetal brain. MIA-related changes in the fetal brain cytokine milieu can cause adverse effects on neurodevelopment, because, besides immune function, cytokines have a signaling function in the brain and participate in the regulation of neurogenesis and synaptogenesis. Several findings also point to the possible pathways on how MIA can be associated with CSF volume. The cytokines can increase CSF secretion, inflammation with bacterial endotoxin decreases CSF flow, and cytokines also might modulate the meningeal lymphatic-glymphatic exchange and CSF reabsorption. In this study, we propose to take advantage of a large number of previously acquired neuroimaging scans of young monkeys from controlled rearing conditions to interrogate the impact of prenatal inflammatory events on EA-CSF volume during infancy. We hypothesize that these well-defined insults will reveal selective effects on the accumulation of CSF in subarachnoid space, which can be detected with structural MRI during the postnatal period. The findings will help to guide similar analyses in pediatric samples and may reveal novel diagnostic tools for use in pediatric practice. Our preliminary results suggested a significant increase in extra-axial CSF volum in monkeys prenatally exposed to bacterial endotoxin.