Stress in pregnancy: a role for neuroactive steroids in protecting the fetal and neonatal brain

Abstract

Stressors during pregnancy can lead to perinatal brain injury resulting in serious neurological impairment. Neuroactive steroid concentrations are elevated during pregnancy and are remarkably high in the fetal brain. In long-gestation species, including humans, these steroids enhance GABAergic inhibition and reduce the possibility of cerebral excitotoxicity during the last third of gestation. The fetal brain responds to acute hypoxia/ischemia by increasing steroid concentrations further as protection against excitotoxic cell death. The placenta has a key role in maintaining neuroactive steroid concentrations in the brain by acting as a source of precursors for neuroactive steroid synthesis. Gestational neuroactive steroid concentrations are needed for normal cell proliferation and cell death in the late gestation brain and a loss of these steroids at preterm birth may adversely affect development and vulnerability to injury.