Glial and neuronal alterations in the nucleus tractus solitarii of sudden infant death syndrome victims.

The factors underlying the sudden infant death syndrome (SIDS) are still unknown, but in recent years much attention has been focused on the central cardiorespiratory control system. In the present work we analyzed the nucleus tractus solitarii (nTS) of 23 SIDS victims and 17 age-matched control cases. We studied the functional and morphological alterations of neurons and glial cells to evaluate the results of possible hypoxic-ischemic injury that could have led to sudden death. Morphometric and immunohistochemical analyses were performed on medullary sections. In the nTS of SIDS victims we observed modifications of both neuronal and glial cells. Brain injury triggers the activation of both astrocytes and microglia, which respond to neuronal damage by characteristic changes that could explain our observations in the nTS of SIDS victims. In our investigation of the nTS of SIDS victims we found a significant increase of reactive astrocytes density, a significantly higher percentage of necrotic cells, an increase of reactive microglial cells density, a significantly higher expression of substance P and the presence of NMDA receptors immunoreactivity. Our results support the hypothesis that there is injury of the nTS neurons in SIDS victims, even if the causes of this damage are still unknown. This neuronal damage may explain why adequate ventilation is often not maintained during hypoxia. Such histological findings have never been thought sufficient to explain SIDS, but the tissue findings could be an indication of the impairment of several pathophysiological mechanisms which may underlie brainstem dysfunction, affecting cardiorespiratory control.

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

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.