title: Pathophysiology of the human locus coeruleus complex in fetal/neonatal sudden unexplained death.
abstract: OBJECTIVE
  We investigated the locus coeruleus complex in the brainstems of 78 subjects aged from 24 gestational weeks to 8 postnatal months, who died of unknown (sudden unexplained fetal and infant deaths) and known causes (controls). The goals of this study were: (1) to obtain  basic information about the morphology of the locus coeruleus complex and the expression of different biological parameters (tyrosine hydroxylase, neuromelanin and apoptosis) during the first phases of human nervous system development; (2) to evaluate possible alterations of this structure  in victims of sudden death; and (3) to verify any correlation with risk factors.
  
  
  METHODS
  All the victims were subjected to a complete autopsy, including an in-depth histological examination of the autonomic nervous system and in particular of the locus coeruleus complex, the target  of this study. Adrenergic neurons were identified by tyrosine hydroxylase (TH) immunohistochemistry and neuromelanin-containing neurons were specifically visualized by the application of Lillie's method. In addition, the activation of programmed cell death (apoptosis) was studied by  investigating DNA fragmentation (TUNEL-positive cells).
  
  
  RESULTS
  Alterations of the noradrenaline system, decreased neuromelanin, hypoplasia, in addition to a high neuronal death rate, were observed almost exclusively in the locus coeruleus complex of fetal and infant sudden deaths,  and were significantly correlated to maternal smoking.
  
  
  CONCLUSIONS
  The developmental defects found in the locus coeruleus complex in victims of sudden unexplained fetal and infant death imply alterations of the vital activities related to the widespread brain connections arising  from this neuronal center, including coordination of the sleep-waking cycle and control of the cardio-respiratory system.
authors: 'Lino Rossi' Research Center for the Study and Prevention of Unexpected Perinatal Death and SIDS Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy.
authors: Anna M
authors: AM
authors: Lavezzi
authors: Graziella
authors: G
authors: Alfonsi
authors: Luigi
authors: L
authors: Matturri
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D020287:In Situ Nick-End Labeling; D007223:Infant; D008125:Locus Coeruleus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008543:Melanins / Q000378:metabolism*; D011247:Pregnancy; D013398:Sudden Infant Death / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D008543:Melanins; C014121:neuromelanin; D014446:Tyrosine 3-Monooxygenase