Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking

Abstract

BackgroundThe ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma) and thoracic spinal cord (central canal ependyma) of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking.ResultsOur results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy.ConclusionsWe conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.

Neuroanatomical dysmorphology of the medial superior olivary nucleus in sudden fetal and infant death

“…As we did in our previous studies (Lavezzi et al, 2005, 2007, 2010, 2012a,b), we ascribe once again the neuropathological findings of this study to smoke absorption in fetal life. Prenatal chronic nicotine exposure primarily alters the development of fetal cholinergic and other neurotransmitter systems, so potentially affecting brainstem centers critical to cardiorespiratory and, more generally, all the autonomic functions control (Duncan et al, 2009).…”

“…The conclusion of this work is that considerable remodeling takes place in the MSO of sudden death victims, in addition to neurological alteration of brainstem and cerebellum previously highlighted by us (Matturri et al, 2002; Lavezzi et al, 2004, 2010, 2012a,b; Matturri and Lavezzi, 2007; Lavezzi and Matturri, 2008a). This leads to attribute to the MSO more important functions than those well-known related to hearing.…”

“…In the course of our neuropathologic investigations on victims of sudden intrauterine unexplained death syndrome (SIUDS) and sudden infant death syndrome (SIDS), we have highlighted specific abnormalities of nuclei and/or structures mediating vital functions, mainly located in the brainstem (Matturri et al, 2002; Lavezzi et al, 2004, 2010, 2012a,b; Matturri and Lavezzi, 2007; Lavezzi and Matturri, 2008a). These neurodevelopmental defects could play a key role in the pathogenetic mechanism of sudden and unexplained perinatal death.…”

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

“…In both SIUDS and SIDS, we have previously highlighted congenital abnormalities of the brain vital centers (Lavezzi and Matturri, 2008a,b; Lavezzi et al, 2004, 2006; Matturri and Lavezzi, 2007; Matturri et al, 2002) and specific developmental defects of the ependyma (Lavezzi et al, 2010) and area postrema (Lavezzi et al, 2012). This study is the first to focus on the development of the fourth ventricle in these pathologies, as there are no reports in the literature on this topic.…”

“…Because the immature blood–CSF barrier (BCSFB) is susceptible to injuries (Rothstein and Levison, 2002), we also investigated a possible link between ontogenetic choroidal alterations and smoking in pregnancy. This anticipated linkage was prompted by defective maturation of the autonomic nervous system observed in sudden‐death victims with smoker mothers (Lavezzi et al, 2005, 2007, 2010, 2012).…”