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

Abstract

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.

The effects of nicotine on human fetal development

“…Other possibilities exist as well. Lavezzi et al () performed histological analysis of human autopsy specimens from unexplained intrauterine fetal demises or unexplained postnatal death and compared them to specimens from perinatal deaths of other, known causes (i.e., infectious etiologies, cardiac abnormalities). They found defective maturation and/or migration of cerebellar Purkinje cells, thought to likely be due to exposure to maternal cigarette smoke (Lavezzi et al, ).…”

“…Lavezzi et al () evaluated autopsy specimens of intrauterine fetal demises or early neonatal deaths. Those fetuses exposed to nicotine showed choroid plexus abnormalities in the 4th ventricle.…”

Emerging Role of the Cerebrospinal Fluid – Neuronal Interface in Neuropathology

“…Interestingly, nicotine has been shown to mediate the function of the choroid plexus. 46,47 Transthyretin, the plasma thyroid hormone transport protein, is produced by the choroid plexus and acts to transport thyoxine across the blood-brain barrier, 48 and nicotine administration has been found to increase the synthesis and release of transthyretin into the CSF. 47 Further, prenatal exposure to nicotine has also been correlated with an increased incidence of pathological features of the fourth ventricle choroid plexus and premature death.…”

“…47 Further, prenatal exposure to nicotine has also been correlated with an increased incidence of pathological features of the fourth ventricle choroid plexus and premature death. 46 However, further investigations will be critical to ascertain whether extracellular factors from the choroid plexus/CSF are important mechanisms that mediate the development and maintenance of drug dependence. “If established, these findings have the potential to redefine our understanding of novel signaling mechanisms within the brain and in doing so, could provide a foundation for more efficacious therapeutic approaches Table 1.”…”

Full-Gestational Exposure to Nicotine and Ethanol Results in Long-Term Dysregulation in the Ventral Tegmental Area

“…Maternal smoking has been correlated with low birth weight, behavioral problems, and initiation of smoking (Ernst et al 2001;Kandel et al 2007). In addition, the occurrence of sudden infant death has been correlated with maternal smoking (Lavezzi et al 2013). Adolescent male children of mothers that smoke demonstrated a four-fold increase in the incidence of conduct disorder compared to male children of nonsmokers (Ernst et al 2001).…”