Substantia Nigra Abnormalities Provide New Insight on the Neural Mechanisms Underlying the Sleep-Arousal Phase Dysfunctions in Sudden Infant Death Syndrome

Abstract

The purpose of this study was to research possible developmental alterations of the substantia nigra (SN) in sudden infant death syndrome (SIDS), a syndrome frequently attributed to arousal failure from sleep. Brain stems of 46 victims of sudden infant death, aged from 1 to about 7 months (4 to 30 postnatal weeks), were investigated. Twenty-six of these cases were diagnosed as SIDS, due to the lack of any pathological finding, while the remaining 20 cases in which the cause of death was determined at autopsy served as controls. Maternal smoking was reported in 77% of SIDS and 10% of controls. Histopathological examination of the SN was done on 5-µm-thick sections of caudal midbrain stained with both hematoxylin-eosin and Klüver-Barrera. Densitometry, immunohistochemistry and histochemistry were applied to highlight the neuronal concentration, the tyrosine hydroxylase (TH) expression, and the presence of neuromelanin (NM) in this structure. Hypoplasia of the pars compacta portion of the SN was observed in 69% of SIDS but never in controls; TH expression was significantly higher in controls than in SIDS; and NM was observed only in 4 infants of the control group but not in SIDS. A significant correlation was found between SIDS, hypoplasia/low neuronal density, low TH expression in the pars compacta, and maternal smoking. Because the SN pars compacta, being the major dopamine brain center, controls many functions, including the sleep-arousal phase, its alterations, especially concurrently with smoking exposure, may contribute to explain the pathogenesis of SIDS that occur in the great part of cases at awakening from sleep.

Immunohistochemical Expression of the Alpha Nicotinic Acetylcholine Receptor 7 in the Human Normal, Diabetic, and Preeclamptic Placenta and Products of Conception

“…The hazardous effects of exposure to tobacco smoking, whether active or passive, during pregnancy include placenta previa (Shobeiri and Jenabi, 2017), placental abruption (Ananth et al, 2016), ectopic pregnancy, early membrane rupture, low birth weight (Bar-Zeev and Solt, 2018), premature birth, sudden perinatal deaths, and stillbirths (Lavezzi et al, 2017;Anderson et al, 2019). We have highlighted these aspects in previous studies as well (Lavezzi et al, 2010(Lavezzi et al, , 2011(Lavezzi et al, , 2020Mehboob, 2017;Mehboob et al, 2017;Muhammad et al, 2018).…”

Sudden Infant Death Syndrome: Beyond Risk Factors

“…A study by Lavezzi et al recently described low tyrosine hydroxylase expression in SIDS cases associated with a delayed development of Substantia Nigra pars compacta (SNpc). Moreover, nicotine absorption in the uterus was related to decreased neuron density in SN [83]. SNpc represents the major dopamine brain center with an important role in regulation of the sleep-arousal cycle [84].…”

“…SNpc represents the major dopamine brain center with an important role in regulation of the sleep-arousal cycle [84]. Therefore, the deficit of dopaminergic neurons, alongside with smoking exposure, may explain SIDS occurrence in the awakening phase in a significant number of cases [83].…”

Medical, Forensic and Social Quandaries of Sudden Infant Death Syndrome Today

“…It has been demonstrated that alveolar bleeding does not correlate with hemorrhage of the nose/mouth or with intrathoracic hemorrhagic petechiae in cases of sudden infant death with adequate sleeping conditions (Krous et al, 2007;Lavezzi et al, 2020;Osawa et al, 2020). Heart tissue samples obtained from the left ventricle show T cell infiltrates that require further immunochemistry and/or biomolecular testing to diagnose acute fatal myocarditis (Bajanowski et al, 2007).…”