Neuropathology of Early Sudden Infant Death Syndrome—Hypoplasia of the Pontine Kolliker-Fuse Nucleus: A Possible Marker of Unexpected Collapse during Skin-to-Skin Care

Lavezzi, Anna Maria; Ferrero, Stefano; Paradiso, Beatrice; Chamitava, Liliya; Piscioli, Francesco; Pusiol, Teresa

doi:10.1055/s-0038-1669398

Cited by 19 publications

(21 citation statements)

References 68 publications

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“…The KF has been shown to impact breathing in anesthetized, ventilated goats during nighttime, as well as anesthetized rats (Bonis et al, 2010;Levitt et al, 2015). Furthermore, hypoplasia of the KF in infants has been implicated in the neuropathology of Sudden Infant Death Syndrome, characterized by failure to stimulate breathing during sleep, indicating a decreased or absent chemosensory response (Lavezzi et al, 2019(Lavezzi et al, , 2004. Taken together, KF modulation can impact respiration during sleep and sedation.…”

Section: State Dependence Of Opioid Action: Implications For Targetinmentioning

confidence: 99%

Kölliker-Fuse/Parabrachial complex mu opioid receptors contribute to fentanyl-induced apnea and respiratory rate depression

Saunders

Levitt

2020

Respiratory Physiology & Neurobiology

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Overdoses caused by the opioid agonist fentanyl have increased exponentially in recent years. Identifying mechanisms to counter progression to fatal respiratory apnea during opioid overdose is desirable, but difficult to study in vivo. The pontine Kölliker-Fuse/Parabrachial complex (KF/PB) provides respiratory drive and contains opioid-sensitive neurons. The contribution of the KF/PB complex to fentanyl-induced apnea was investigated using the in situ arterially perfused preparation of rat. Systemic application of fentanyl resulted in concentration-dependent respiratory disturbances. At low concentrations, respiratory rate slowed and subsequently transitioned to an apneustic-like, 2-phase pattern. Higher concentrations caused prolonged apnea, interrupted by occasional apneustic-like bursts. Application of CTAP, a selective mu opioid receptor antagonist, directly into the KF/PB complex reversed and prevented fentanyl-induced apnea by increasing the frequency of apneustic-like bursting. These results demonstrate that countering opioid effects in the KF/PB complex is sufficient to restore phasic respiratory output at a rate similar to prefentanyl conditions, which could be beneficial in opioid overdose.

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Section: State Dependence Of Opioid Action: Implications For Targetinmentioning

confidence: 99%

Kölliker-Fuse/Parabrachial complex mu opioid receptors contribute to fentanyl-induced apnea and respiratory rate depression

Saunders

Levitt

2020

Respiratory Physiology & Neurobiology

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“…The study focused on the examination of the brainstem, where the control centres for vital body functions are located. The procedure, which has already been described in depth in some of our previous articles (23)(24)(25), is again summarized below. Transverse serial sections from each specimen were made at intervals of 60 µm.…”

Section: Antomopathological Proceduresmentioning

confidence: 99%

Neurobiological Alterations Of The Substantia Nigra In Sudden Infant Death Syndrome

Lavezzi¹,

Mehboob²,

Alfonsi³

et al. 2020

Preprint

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Background - The purpose of this study was to research possible morphological and functional alterations of the substantia nigra in SIDS. Methods - Brainstems of 46 victims of sudden infant death, aged from 1 to 7 months, 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 10% of controls and 77% of SIDS. Histopathological examination of the substantia nigra was done on midbrain 5-µm-thick sections stained with hematoxylin-eosin and Klüver-Barrera. Densitometry, immunohistochemistry and histochemistry were applied to highlight the neuronal concentration, the expression of tyrosine hydroxylase and neuromelanin, respectively. Results - Hypoplasia of the pars compacta of the substantia nigra was observed in SIDS but not in controls. Tyrosine hydroxylase expression in the substantia nigra was significantly higher in controls than in SIDS. Neuromelanin was observed as dark granules only in 4 infants of the control group but never in SIDS. A significant correlation was found between hypoplasia/low neuronal density, low tyrosine hydroxylase expression in the substantia nigra pars compacta and maternal smoking. Conclusion - The substantia nigra pars compacta, that is the main dopamine center in the brain, is involved in the control of many functions, including the sleep-arousal phase, and hence, its structural and/or functional alterations may explain the pathogenesis of SIDS, that often occurs during sleep. This study also indicates that maternal smoking can may have strongly influenced the SN altered development. Trial registration – not applicable for this study

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“…We observed hypodevelopments (hypoplasia/agenesis) of different nervous centers, all components of the RN, and precisely: hypoplasia, with a few immature neurons, or agenesis of the Kölliker-Fuse nucleus in the rostral pons and caudal mesencephalon [28,29];…”

Section: Morphological Alterationsmentioning

confidence: 90%

Sudden Intrauterine Unexplained Death: Time To Adopt Uniform Postmortem Investigative Guidelines?

Lavezzi

Piscioli

Pusiol

et al. 2019

Preprint

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Background: In developed countries, one in 100–200 pregnancies ends in stillbirth, in the great part unexplained. The evenness and standardisation of the diagnostic criteria are prerequisites to understand the pathogenesis of these deaths. The core goal of this article is to propose new investigative post-mortem guidelines that should be adopted in all the Institutions especially when a fetal death, after a routine autopsy procedure, is diagnosed as “unexplained”. Methods: Updated investigative guidelines for the examination of unexplained stillbirths, prevalently focused on the histological examination of the brainstem, where the main centers that are involved in monitoring the vital functions are located, are here presented. A section of this protocol concerns the Immunohistochemical evaluation of specific functional markers such as the neuronal nuclear antigen, nicotinic acetylcholine receptors, serotonin, orexin, apoptosis and gliosis. The important role of risk factors, having regard in particular to maternal smoking and air pollution is also contemplated in these guidelines. Results: Specific morphological and/or functional alterations of vital brainstem structures have been found with high incidence in about 100 cases of unexplained fetal death sent to the “Lino Rossi Research Center” of the Milan University according to the Italian law. These alterations were rarely detected in a group of control cases. Conclusions: We hope this protocol can be adopted in all the Institutions notably for the examination of unexplained fetal deaths, in order to make uniform investigations. This will lead to identify a plausible explanation of the pathogenetic mechanism behind the unexplained fetal deaths and to design preventive strategies to decrease the incidence of these very distressing events for both parents and clinicians .

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Neuropathology of Early Sudden Infant Death Syndrome—Hypoplasia of the Pontine Kolliker-Fuse Nucleus: A Possible Marker of Unexpected Collapse during Skin-to-Skin Care

Cited by 19 publications

References 68 publications

Kölliker-Fuse/Parabrachial complex mu opioid receptors contribute to fentanyl-induced apnea and respiratory rate depression

Kölliker-Fuse/Parabrachial complex mu opioid receptors contribute to fentanyl-induced apnea and respiratory rate depression

Neurobiological Alterations Of The Substantia Nigra In Sudden Infant Death Syndrome

Sudden Intrauterine Unexplained Death: Time To Adopt Uniform Postmortem Investigative Guidelines?

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