Identification of neurons responding to hypoxia in sudden infant death syndrome

The pathogenesis of sudden infant death syndrome (SIDS) is still not understood, although one of the most credited current hypotheses is the respiratory theory. Considerable evidence has been assembled suggesting that hypoxia in human infants produces an initial increase in ventilation, after which respiration is rapidly inhibited. We investigated the expression of the c-fos proto-oncogene, a marker of activated neurons, particularly by hypoxia, in the medulla oblongata nuclei involved in breathing after birth, with special reference to SIDS. We utilized c-fos protein immunohistochemistry on serial transverse sections of medulla oblongata from 22 SIDS victims. In 60% of the analyzed cases, we observed numerous positive c-fos neurons in the dorsal motor nucleus of the vagal nerve. In control cases, the immunohistochemical labeling was negative or very low. The c-fos protein was expressed in the rostral-intermediate portion of the dorsal motor vagal nucleus, where motoneurons with respiratory-related activity are located. The positive c-fos immunoreactivity observed in SIDS suggests that the neurons of the dorsal motor vagal nucleus involved in the regulation of breathing are able to yield an intense, immediate ventilatory response to hypoxia. Our results support the respiratory theory of SIDS.