The Impact of Systemic Inflammation on Neurodevelopment

Inflammatory mediators affect the brain during development. Neurodevelopmental disorders such as autism spectrum disorders, cognitive impairment, cerebral palsy, epilepsy, and schizophrenia have been linked to early life inflammation. Recent advances have shown the effects of systemic inflammation on children’s neurodevelopment. We discuss the potential mechanisms by which inflammatory molecules can exert their effects on the developing brain and consider the roles of MHC class I molecules, the HPA axis, glial cells, and monoamine metabolism. Methods to prevent the effects of cytokine imbalance may lead to the development of new therapeutics for neuropsychiatric disorders. Future research should focus on identifying at-risk individuals and early effective interventions to prevent long-term neurodevelopmental disabilities. Maternal immune activation (MIA) refers to the activation of a pregnant mother’s immune system in response to an insult such as an infection. While MIA is generally protective, MIA may also be a risk factor for neurological conditions in the child later on. Elevated concentrations of inflammation-related cytokines, such as IL-6, in maternal serum in utero as well as in children early in life are associated with worse neurodevelopmental outcomes, while IL-4 appeared protective. Dysbiotic microbiota and environmental enteropathy have been connected to inflammation in the child during the first 2 years of life and poor neurodevelopmental outcomes. Microglia (macrophage-like cells in the developing brain) are a potential therapeutic target given that they are a major hub of proinflammatory activity.