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Delayed neuronal maturation of the medullary arcuate nucleus in sudden infant death syndrome

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Abstract

Recently, quantitative abnormalities in neuronal populations derived from the rhombic lip (inferior olive nucleus of the brain stem and external granular layer of the cerebellum) have been reported in victims of the sudden infant death syndrome (SIDS). In this study we examined the arcuate nucleus (ARCn) of 35 SIDS victims and 25 controls, to determine neuronal abnormalities involving this nucleus in SIDS. Computer-assisted cell evaluation was made on sections stained with hematoxylin and eosin to study the neuronal dimensions (nuclear and cytoplasmic area, nuclear/cytoplasmic ratio), the form factor and the density of reactive astrocytes. There was a significant reduction of the neuronal area (nuclear and cytoplasmic) in SIDS victims compared with controls. The neuronal populations of SIDS victims had a significantly higher form factor, index of immaturity. The SIDS victims were divided into two groups on the basis of ARCn development: 18 SIDS-A cases with a well-developed ARCn and 17 SIDS-B cases with severe bilateral hypoplasia. The results of our research indicate that the developmental defect is characterized by a reduction in size of the ARC neurons and by neuronal depletion. In SIDS the ARCn has the histomorphological features of neuronal immaturity, and there is a marked reduction of all quantitative cell parameters and lower astrocytes density with respect to controls. On the basis of the morphometric results of the arcuate neuronal populations, we hypothesize that infants whose neurons have failed to reach full maturity are at risk for SIDS because they are unable to develop appropriate cardioventilatory control.

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Acknowledgements

This study was supported by MURST Cofin 2000 (project MM06153578: "Pathologic Study of Late Fetal Unexplained Death-Stillbirth") and by the Lombardy Region "Program of Research and Intervention for the Reduction of the Risk of Sudden Infant Death and Unexpected Fetal Death"(project 49210-24/02/00)

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Authors and Affiliations

  1. Institute of Pathology, University of Milan, Via Commenda 19, 20122, Milan, Italy

    Bruna Biondo, AnnaMaria Lavezzi, Delfina Tosi, Paola Turconi & Luigi Matturri

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  1. Bruna Biondo
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  2. AnnaMaria Lavezzi
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  3. Delfina Tosi
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  4. Paola Turconi
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  5. Luigi Matturri
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Correspondence to Luigi Matturri.

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Biondo, B., Lavezzi, A., Tosi, D. et al. Delayed neuronal maturation of the medullary arcuate nucleus in sudden infant death syndrome. Acta Neuropathol 106, 545–551 (2003). https://doi.org/10.1007/s00401-003-0757-3

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  • DOI: https://doi.org/10.1007/s00401-003-0757-3

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