title: Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking.
abstract: BACKGROUND
  The 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.
  
  
  RESULTS
  Our 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Department of Surgical, Reconstructive and Diagnostic Sciences, Lino Rossi Research Center, University of Milan, Via della Commenda 19, 20122 Milan, Italy. anna.lavezzi@unimi.it
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lavezzi
authors.forename: Melissa F
authors.initials: MF
authors.lastname: Corna
authors.forename: Luigi
authors.initials: L
authors.lastname: Matturri
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004805:Ependyma / Q000002:abnormalities / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005313:Fetal Death / Q000139:chemically induced* / Q000503:physiopathology; D020546:Fourth Ventricle / Q000002:abnormalities / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects*; D013398:Sudden Infant Death / Q000209:etiology* / Q000473:pathology