Developmental Brain Injury and Social Determinants of Health: Opportunities to Combine Preclinical Models for Mechanistic Insights into Recovery

Abstract

Epidemiological studies show that social determinants of health are amongst the strongest factors associated with developmental outcomes after prenatal and perinatal brain injuries, even when controlling for the severity of the initial injury. Elevated socioeconomic status and a higher level of parental education correlate with improved neurologic function after premature birth. Conversely, children experiencing early life adversity have worse outcomes after developmental brain injuries. Animal models have provided vital insight into mechanisms perturbed by developmental brain injuries, which have indicated directions for novel therapeutics or interventions. Animal models have also been used to learn how social environments affect brain maturation through enriched environments and early adverse conditions. We recognize animal models cannot fully recapitulate human social circumstances. However, we posit that mechanistic studies combining models of developmental brain injuries and early-life social environments will provide insight into pathways important for recovery. Some studies combining enriched environments with neonatal hypoxic injury models have shown improvements in developmental outcomes, but further studies are needed to understand the mechanisms underlying these improvements. By contrast, there have been more limited studies of the effects of adverse conditions on developmental brain injury extent and recovery. Uncovering the biological underpinnings for early life social experiences has translational relevance, enabling the development of novel strategies to improve outcomes through lifelong treatment. With the emergence of new technologies to analyze subtle molecular and behavioral phenotypes, here we discuss the opportunities for combining animal models of developmental brain injury with social construct models to deconvolute the complex interactions between injury, recovery, and social inequity.