50 research outputs found
From fix to fit into the autoptic human brains
No full textFormalin-fixed, paraffinembedded (FFPE) human brain tissues are very often stored in formalin for long time. Formalin fixation reduces immunostaining, and the DNA/RNA extraction from FFPE brain tissue becomes suboptimal. At present, there are different protocols of fixation and several procedures and kits to extract DNA/RNA from paraffin embedding tissue, but a gold standard protocol remains distant. In this study, we analyzed four types of fixation systems and compared histo and immuno-staining. Based on our results, we propose a modified method of combined fixation in formalin and formic acid for the autoptic adult brain to obtain easy, fast, safe and efficient immunolabelling of long-stored FFPE tissue. In particular, we have achieved an improved preservation of cellular morphology and obtained success in postmortem immunostaining for NeuN. This nuclear antigen is an important marker for mapping neurons, for example, to evaluate the histopathology of temporal lobe epilepsy or to draw the topography of cardiorespiratory brainstem nuclei in sudden infant death syndrome (SIDS). However, NeuN staining is frequently faint or lost in postmortem human brain tissues. In addition, we attained Fluoro Jade C staining, a marker of neurodegeneration, and immunofluorescent staining for stem cell antigens in the postnatal human brain, utilizing custom fit fixation procedures
Neuroanatomical dysmorphology of the medial superior olivary nucleus in sudden fetal and infant death
No full textThis study expands our understanding of the organization of the human caudal pons, providing a morphologic characterization of the medial superior olivary nucleus, component of the superior olivary complex, that plays an important role in the processing of acoustic information.
We examined victims of sudden unexplained fetal and infant death and controls (n=75), from 25 gestational weeks to 8 months of postnatal age, by complete autopsy and in-depth autonomic nervous system histological examination, particularly of the medial superior olivary nucleus, the focus of this study.
Peculiar cytoarchitectural features of the medial superior olivary nucleus were found in sudden death cases, such as hypoplasia/agenesis and immature hypercellularity, frequently related to dysgenesis of contiguous structures involved in respiratory rhythm-generating circuit, in particular to hypoplasia of the retrotrapezoid and the facial nuclei.
We propose the involvement of this nucleus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities. Besides, we highlight the fundamental role of the maternal smoking in pregnancy as etiological factor in the dysmorphic neuroanatomical development of the medial superior olivary nucleus
Developmental alterations of the spinal trigeminal nucleus disclosed by substance P immunohistochemistry in fetal and infant sudden unexplained deaths
No full textWe investigated the immunohistochemical expression of substance P (SP) in the brainstems of 56 subjects aged from 17 gestational weeks to 10 postnatal months, who died of unknown (sudden unexplained perinatal deaths and SIDS) and known causes (controls). The goals of this study were: 1) to obtain basic information about the expression of SP during the first phases of human nervous system development; 2) to evaluate whether there are alterations of this neuromodulator in victims of sudden death; 3) to verify any correlation with maternal cigarette smoking.
Immunohistochemistry demonstrated SP-immunoreactivity in the caudal trigeminal nucleus area, with a progressive increase in the density of SP-positive fibers of the corresponding tract during normal development from fetal life to the first postnatal months. Delineation of the structure of the human trigeminal nucleus, little investigated so far, provided essential data on its morphologic and functional development.
Instead, a negative or low SP expression was detectable in the fibers of this tract in a wide subset of SIDS victims and, conversely, a high SP-expression in a wide subset of sudden fetal deaths. We postulate, on the basis of these results, that SP has a functional importance in the early phases of central nervous system development and in the regulation of autonomic functions.
In addition, the observation of a significant correlation between sudden unexplained death, altered SP staining and maternal smoking leads us to suggest a close relation between the absorption of cigarette smoke in utero and a decreased functional activity of the trigeminal nucleus, that can trigger sudden death of the fetus during pregnancy or of the infant in the first months of life
Unexplained stillbirth versus SIDS: common congenital diseases of the autonomic nervous system--pathology and nosology
No full textObjective: To contribute to a more balanced assessment of the morphological substrates underlying
unexplained perinatal death and SIDS.
Methods: In-depth histological, immunohistochemical and genetic examinations were performed on the
autonomic nervous and cardiac conduction systems in 95 unexpected perinatal deaths, 140 SIDS and 78
controls (44 infants and 34 perinatal death victims).
Results: The study revealed the localization and the nature of a variety of specific congenital abnormalities of
the autonomic nervous system, central and peripheral, and of the cardiac conduction system that represent
the morphological substrates of the pathophysiological mechanism of sudden fetal death and SIDS.
Conclusions: The observation of similar anomalies of the autonomic nervous and the cardiac conduction
systems in both unexplained perinatal deaths and SIDS indicates their common congenital nature. Therefore,
the definitions of these deaths, currently nosographically distinct, should be unified.
© 2010 Elsevier Ireland Ltd. All rights reserved
Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking
No full textAbstract Background The ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma) and thoracic spinal cord (central canal ependyma) of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking. Results Our results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy. Conclusions We conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.</p
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
No full textObjective To find a possible pathogenetic mechanism of the early sudden infant death occurring in newborns during the skin-to-skin care (SSC), through the examination of neuronal centers regulating the vital activities. Study Design This is an in-depth examination of the brain stem in 22 healthy term newborns, suddenly died in the first hour of life without the identification of a cause at autopsy (early sudden infant death syndrome [eSIDS]), 12 of them concomitantly with SSC, and 10 with age-matched controls died of known pathology. Results Developmental alterations of neuronal structures of the brain stem were highlighted in 19 of the 22 eSIDS, but not in control. The hypoplasia of the pontine Kolliker-Fuse nucleus (KFN), an important respiratory center, was diagnosed at the histological examination, validated by morphometric quantifications, in 11 of the 12 eSIDS while they were placed on the mother's chest and in 2 of the 10 SSC unrelated neonatal deaths. Conclusion The delayed development of the KFN could represent a specific finding of eSIDS occurring during SSC. Therefore, it is necessary to point out that the SSC represents a further risk factor that must be added to others already known for sudden infant death syndrome. Then this practice needs appropriate monitoring strategies of the infant's conditions
Sudden Infant Death With Area Postrema Lesion Likely Due to Wrong Use of Insecticide
No full textWe report a noteworthy case of a 7-month-old infant who suddenly and abstract
unexpectedly died during her sleep. After a complete postmortem examination,
review of the clinical history, and detailed death scene investigation, the death
remained unexplained, leading to a diagnosis of sudden infant death syndrome.
However, an extensive review of the brainstem neuropathology revealed a severe
alteration in the area postrema (a highly vascular structure lying at the base of
the fourth ventricle outside of the blood-brain barrier). The alteration was
likely due to massive and repeated to a common household insecticide in the last
few weeks of life. These results provide an explanation for this sudden infant
death, allowing a differential diagnosis from sudden infant death syndrome
Severe intra- and periventricular hemorrhage: role of arteriolosclerosis related to maternal smoke
No full textThe authors aimed to describe the atherosclerotic lesions of the cerebral arterioles, as a substrate of their rupture and bleeding for ests.
The study was performed on brain of 9 caucasian fetal victims of intra- and periventricular hemorrhage, all grade IV, and 9 control cases.
In the 9 victims of hemorrhage the arteriolar wall structure was altered, focally transformed into a deposit of amorphous eosinophilic material. Such changes often affected the full-thickness of the wall, causing rupture and hemorrhage. In 8 of these cases and in 2 victims of the control group the mothers were heavy cigarette smokers (15-20 cigarettes/day) before and during pregnancy.
The authors conclude that intra- and periventricular haemorrhage can be ascribed to the toxic effects of prenatal absorption of nicotine
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
Authorised access web portal for Italian data bank on sudden unexpected perinatal and infant death
No full textSudden infant death syndrome (SIDS) is common during the first year of life and affects 0.40 every 1,000 births. Stillbirths are seven times more common than SIDS; in 40–80% of cases remain unexplained and are categorised as sudden intrauterine unexpected death syndrome. In 2006 Italy passed legislation that fetuses, and infants, from 25 weeks of gestation to one postnatal year, that died suddenly and unexpectedly should be sent to the University of Milan, Italy, for an in-depth diagnostic post-mortem with parental permission. The “Lino Rossi” Research Center is currently developing the technical specifications for a web portal (http://users.unimi.it/centrolinorossi) for its national data bank registry, which has been set up to centralise records retrieved from regions across Italy. This will record all post-mortem findings, together with clinical information about the pregnancy, fetal development, delivery, environmental conditions and the family situation when the death occurred. The privacy and confidentiality of the data are ensured, in accordance with European legislation
