The correlation between microtubule-associated protein 2 in the brainstem of SIDS victims and physiological data on sleep apnea

Abstract

Background: Microtubule-associated protein 2 (MAP2), a cytoskeletal protein of the neuron, is a marker of early ischemic neuronal damage. As a chronic hypoxic situation exists in the brains of victims of the sudden infant death syndrome (SIDS), the correlation between MAP2-positive neurons or dendritic spines in the brainstem and sleep apnea was investigated in SIDS, which is still the main cause of postneonatal infant death. Materials and methods: Twenty-seven thousand infants were studied prospectively to characterize their sleep–wake behavior and amongst these, 38 infants died under 6 months of age. They included 26 cases of SIDS. The frequency and duration of sleep apneae were analyzed. The brainstem material was collected and immunohistochemistry of MAP2 was carried out. The density of MAP2-positive neurons, dendrites, and dendritic spines were measured quantitatively. Correlation analyses were carried out between the MAP2-associated pathological data and the physiological data of sleep apnea. Results: One negative correlation between the density of MAP2-positive endrites in the pars compacta of pedunculo-pontine tegmentum nucleus (PPTNc) and the duration of obstructive apnea ( P=0.017) and two SIDS-specific positive correlations between the density of MAP2-positive dendrites in the pars dissipata of pedunculo-pontine tegmentum nucleus (PPTNd) and the duration of central apnea ( P=0.005) and between the dorsal raphe and the frequency of obstructive apnea were found in SIDS victims. The density of MAP2-positive dendritic spines in PPTNc was significantly higher in SIDS than in control ( P=0.034). Conclusions: The significant correlations with the MAP2-positive findings in the midbrain arousal pathway and the characteristics of sleep apnea in SIDS victims were in agreement with the association with apnea and arousal-deficiency in SIDS.