26 research outputs found
IL NUCLEO RETROTRAPEZOIDE UMANO: ALTERAZIONI CONGENITE IN CASI DI MORTE INASPETTATA PERINATALE E DEL LATTANTE
No full textEfficient uptake of oxygen and removal of carbon dioxide are essential conditions for life, and for normal growth and development in many species. Neurons in the brainstem chemoreceptors are distributed in specialized cental detect and regulate the presence of CO2 and/or changes in pH through a variety of responses. In so doing, these central chemoreceptors regulate extrauterin breathing actively responding through a variety of responses. Differences between prenatal and postnatal chemoreception appear to be primarily dependent on central inhibition in fetal life of the ventilatory responses to hypoxia and/or hypercapnia, with localization to the rostral lateral pons in the parabrachial/Kölliker-Fuse complex. The inhibitory effects of this complex are significantly reduced after the birth. Thus, chemoreception would function differently in the fetus than in the newborn, and birth would be associated with an abrupt change in the parabrachial/Kölliker-Fuse complex function.
Experimental studies on animal models have identified the retrotrapezoide nucleus (RTN) as one of the main sites of central chemoreception and respiratory control. Numerous studies have RTN elected as one of the most important regions mediating central chemoreception. The RTN appears to integrate central and peripheral chemoreceptor information, providing an important role in respiratory function. The objectives of the study were: to locate and describe the cytoarchitecture of the nucleus retrotrapezoide (RTN) in the human fetus and infant, and ensure that the RTN, given its essential role in animal studies for the maintenance of respiration, showed abnormalities in victims of death sudden unexplained intrauterine (SIUD) and sudden infant syndrome (SIDS). Many studies have shown the expression of a transcription factor in neurons of the NRT: PHOX2B gene that was used as a marker. Three groups of Italians Caucasian children were autopsied, and by using immunohistochemistry has been studied the expression of PHOX2B gene. A group of positive neurons has been identified located within the caudal pons, contiguous to the facial/parafacial (PFN) complex, potentially the human homologous RTN (hRTN), already known in the mouse.
In 71% of the cases has been observed structural abnormalities and/or expression of the PHOX2B gene hRTN vs. 10% of controls. In 85% of cases with alterations was also observed agenesis of the complex PFN. This study was conducted to determine the possibility of tracing the anatomical borders and cytoarchitecture of the human homologue of the RTN, by using immunohistochemical techniques. Views longstanding literature regarding the involvement of cardio-respiratory alterations in the sudden infant death syndrome (SIDS) pathogenesis, and the role of hNRT in regulation of breathing chemoreception, it has been hypothesized that abnormalities of development the RTN can play a critical role in SIDS and SIUD etiology
Neuronal nuclear antigen (NeuN): a useful marker of neuronal immaturity in sudden unexplained perinatal death
No full textINTRODUCTION - In the developing brain neuronal differentiation is associated with permanent exit from the mitotic cycle. Neuronal nuclear antigen (NeuN) is a nuclear protein widely expressed in the mature postmitotic neurons.
METHODS - We applied NeuN immunocytochemistry in 65 cases of perinatal death (16 victims of sudden intrauterine unexplained death syndrome/SIUDS, 19 of sudden infant death syndrome/SIDS and 30 Controls) to test the physiological status of the brain neurons. In addition we applied both TUNEL and activated-Caspase 3 immunohistochemical methods in order to highlight neuronal death and evaluate a possible relation between decreased NeuN expression and apoptotic outcome. We also attempted to see whether or not NeuN pathological changes can be related to cigarette smoke absorption in pregnancy.
RESULTS - NeuN staining was considerably reduced or lost in SIUDS/SIDS compared to controls. However neurons with decreased NeuN-labeling showed no sign of apoptosis. A significant association was found between NeuN depletion and maternal smoking.
CONCLUSION – Altered NeuN expression can be a marker of immature and/or suffering neurons. The exclusive presence of this pattern of expression in SIUDS/SIDS victims, leads us to recommend the NeuN immunohistochemistry as a routine method in neuropathological protocols to convalidate a diagnosis of sudden perinatal death
Disruption of the brain-derived neurotrophic factor (BDNF) immunoreactivity in the human Kölliker-Fuse nucleus in victims of unexplained fetal and infant death
No full textExperimental studies have demonstrated that the neurotrophin brain-derived neutrophic factor (BDNF) is required for the appropriate development of the central respiratory network, a neuronal complex in the brainstem of vital importance to sustaining life. The pontine Kölliker-Fuse nucleus (KFN) is a fundamental component of this circuitry with strong implications in the pre- and postnatal breathing control. This study provides detailed account for the cytoarchitecture, the physiology and the BDNF behaviour of the human KFN in perinatal age. We applied immunohistochemistry in formalin-fixed and paraffin-embedded brainstem samples (from 45 fetuses and newborns died of both known and unknown causes), to analyze BDNF, gliosis and apoptosis patterns of manifestation. The KFN showed clear signs of developmental immaturity, prevalently associated to BDNF altered expression, in high percentages of sudden intrauterine unexplained death syndrome (SIUDS) and sudden infant death syndrome (SIDS) victims. Our results indicate that BDNF pathway dysfunctions can derange the normal KFN development so preventing the breathing control in the sudden perinatal death.The data presented here are also relevant to a better understanding of how the BDNF expression in the KFN can be involved in several human respiratory pathologies such as the Rett’s and the congenital central hypoventilation syndromes
Possible role of the α7 nicotinic receptors in mediating nicotine’s effect on developing lung – implications in unexplained human perinatal death
No full textBackground
It is well known that maternal smoking during pregnancy is very harmful to the fetus. Prenatal nicotine absorption, in particular, is associated with alterations in lung development and functions at birth and with respiratory disorders in infancy. Many of the pulmonary disorders are mediated by the interaction of nicotine with the nicotinic receptors (nAChRs), above all with the alpha7 nAChRs subunits that are widely expressed in the developing lung. To determine whether the lung hypoplasia frequently observed in victims of sudden fetal and neonatal death with a smoker mother may result from nicotine interacting with lung nicotinic receptors, we investigated by immunohistochemistry the possible presence of this specific nAChR subunit overexpression in these pathologies.
Methods
In lung histological sections from 45 subjects who died of sudden intrauterine unexplained death syndrome (SIUDS) and 15 subjects who died of sudden infant death syndrome (SIDS), we applied the radial alveolar count (RAC) to evaluate the degree of lung maturation, and the immunohistochemical technique for nAChRs, in particular for the alpha7 nAChR subunit. In the same cases, an in-depth study of the autonomic nervous system was performed to highlight possible developmental alterations of the main vital centers located in the brainstem.
Results
We diagnosed a "lung hypoplasia", on the basis of RAC values lower than the normal reference values, in the 63% of SIUDS/SIDS group and in 8% of controls. In addition, we observed a significantly higher incidence of strong alpha7 nAChR immunostaining in lung epithelial cells and lung vessel walls in sudden fetal and infant death cases with a smoker mother than in age-matched controls. Hypoplasia of the raphe, the parafacial, the Kolliker-Fuse, the arcuate and the pre-Botzinger nuclei was simultaneously present in the brainstem of these victims.
Conclusions
These findings demonstrate that when crossing the placenta, nicotine can interact with nicotinic receptors of both neuronal and non-neuronal cells, leading to both lung and nervous system defective development. This work stresses the importance of implementing preventable measures to decrease the noxious potential of nicotine in pregnancy
Neuropathology of the intermediolateral nucleus of the spinal cord in sudden unexplained perinatal and infant death
No full textExperimental studies have demonstrated that breathing activity in rats is generated early in embryonic stages in rostral spinal cord, precisely in the intermediolateral nucleus, then establishing a spinal cord-brainstem network.
In this study we aimed to individuate and to define the developmental steps of the intermediolateral nucleus, still inadequately known in humans, in the thoracic spinal cord of a large series of perinatal and infant death victims, aged from 17 gestational weeks to 10 months of life. Besides we investigated a possible link between alterations of this nucleus and sudden unexplained perinatal and infant death.
The normal developmental pattern of the human intermediolateral nucleus consists of a progressive maturation of its neurons, that change from a round to a polygonal shape with long axons and significantly decrease in number.
Various degrees of intermediolateral nucleus hypodevelopment (neuronal immaturity in a normal structure/hypoplasia/agenesis) were found almost exclusively in unexplained fetal and infant death victims. Besides, a significant correlation was found between maternal smoking in pregnancy and the neuropathological results.
In conclusion this work underlines the negative effects of prenatal nicotine exposure on the development of autonomic nervous centers checking the vital functions, already in early gestational stages, when the integrity of the intermediolateral nucleus is indispensable for the first breathing burst
Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia
No full textAbstract Background Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia. Methods Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments. Results Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells. Conclusions We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.</p
Pesticide exposure during pregnancy, like nicotine, affects the brainstem α7 nicotinic acetylcholine receptor expression, increasing the risk of sudden unexplained perinatal death
No full textThis study indicates the impact of nicotine and pesticides (organochlorine and organophosphate insecticides
used in agriculture) on neuronal α7-nicotinic acetylcholine receptor expression in brainstem regions receiving
cholinergic projections in human perinatal life. An in-depth anatomopathological examination of the autonomic
nervous systemand immunohistochemistry to analyze the α7-nicotinic acetylcholine receptor expression in the
brainstem from 44 fetuses and newborns were performed. In addition, the presence of selected agricultural
pesticides in cerebral cortex samples of the victims was determined by specific analytical procedures.
Hypodevelopment of brainstem structures checking the vital functions, frequently associated with
α7-nicotinic acetylcholine receptor immunopositivity and smoke absorption in pregnancy, was observed in
high percentages of victims of sudden unexpected perinatal death. In nearly 30% of cases however the mothers
never smoked, but lived in rural areas. The search for pesticides highlighted in many of these cases traces of
both organochlorine and organophosphate pesticides. We detain that exposition to pesticides in pregnancy
produces homologous actions to those of nicotine on neuronal α7-nicotinic acetylcholine receptor, allowing to
developmental alterations of brainstem vital centers in victims of sudden unexplained death
DEVELOPMENTAL ALTERATIONS OF THE RESPIRATORY HUMAN RETROTRAPEZOID NUCLEUS IN SUDDEN UNEXPLAINED FETAL AND INFANT DEATH
No full textThe study aims were twofold: 1) identify the localization and the cytoarchitecture of the retrotrapezoid nucleus in the human fetus and infant and 2) ascertain if the RTN, given its essential role in animal studies for the maintenance of breathing and chemoreception, showed abnormalities in victims of sudden perinatal death (sudden intrauterine unexplained death/SIUD– and sudden infant death syndrome/SIDS). We examined SIDS and SIUD cases and Controls (n=58) from 34 gestational weeks to 8 months of postnatal age by complete autopsy, in-depth autonomic nervous system histological examination, and immunohistochemical analysis of the PHOX2B gene, a transcriptional factor involved in Congenital Central Hypoventilation Syndrome that has been defined as a marker of rat RTN neurons.
We identified a group of PHOX2B-immunopositive neurons within the caudal pons, contiguous to the facial/parafacial complex, in 90% of Controls, likely the homologous human RTN (hRTN). We observed structural and/or PHOX2B-expression abnormalities of the hRTN in 71% of SIUD/SIDS cases vs. 10% of Controls (p<0.05).
In conclusion we suggest that developmental abnormalities of the hRTN may seriously compromise chemoreception control, playing a critical role in the pathogenesis of both SIUD and SIDS
El Tlacuache Núm. 511 (2012). 511 Año 13 (2012) marzo. El Tlacuache
No full textCambio de estación y la migración de ballenas por Eduardo Corna Martínez. -Pasado y presente de los aprovechamientos costeros en la Península de Baja California por Ricardo Claudio Pacheco Bribiesca
A Si/SiGe based quantum dot with floating gates for scalability
No full textGreen Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.QCD/Vandersypen LabQN/Veldhorst LabQID/Ishihara LabQuantum Circuit Architectures and TechnologyQN/Vandersypen La
