Vulnerability of fourth ventricle choroid plexus in sudden unexplained fetal and infant death syndromes related to smoking mothers

•We examined the human fourth ventricle choroid plexus in subjects died in perinatal period of both known and unknown cause.•Victims of sudden unexplained fetal and infant death shoved many neuropathological alterations of this structure.•These alterations were significantly related to maternal smoking.•The role of the fourth ventricle choroid plexus in the central autonomic nervous system development was outlined.

The human choroid plexuses in the ventricular system represent the main source of cerebrospinal fluid secretion and constitute a major barrier interface that controls the brain's environment. The present study focused on the choroid plexus of the fourth ventricle, the main cavity of the brainstem containing important nuclei and/or structures mediating autonomic vital functions.In serial sections of 84 brainstems of subjects aged from 17 gestational weeks to 8 postnatal months of life, the deaths due to both known and unknown causes, we examined the cytoarchitecture and the developmental steps of the fourth ventricle choroid plexus to determine whether this structure shows morphological and/or functional alterations in unexplained perinatal deaths (Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death Syndrome).High incidence of histological and immunohistochemical alterations (prevalence of epithelial dark cells, the presence of cystic cells in the stroma, decreased number of blood capillaries, hyperexpression of Substance P and apoptosis) were prevalently observed in unexplained death victims (p < 0.05 vs. controls). A significant correlation was found between maternal smoking in pregnancy and choroidal neuropathological parameters (p < 0.01).This work underscores the negative effects of prenatal exposure to nicotine on the development of the autonomic nervous system, and in particular of the fourth ventricle choroid plexus that is a very vulnerable structure in the developing CSF–brain system.