Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia

Lavezzi, Anna Maria; Mohorović, Lucijan; Alfonsi, Graziella; Corna, Melissa F.; Matturri, Luigi

doi:10.1186/1471-2431-11-62

Cited by 15 publications

(11 citation statements)

References 51 publications

(47 reference statements)

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“…The conducted proper research found that neonatal jaundice incidence (p=0.034), heart murmur at a later age (p=0.011) and mild disorders in children and adults such as dyslalia and learning/memory impairments (p=0.002) were significantly higher than in children and adults of control mothers without pregnancy methemoglobinemia [17]. Lavezzi AM, Mohorovic L, et al recently presented the findings confirmed by pathohistological technique that under the adverse conditions, ferric iron positivity in capillary endothelial cells of the blood-brain barrier in the fetus rises, also resulting in preterm birth, stillbirth or early neonatal death [18]. The application of the Blue Prussian method highlighted the accumulations of blue granulations, indicative for non-heme Fe 3+ positive reactions, in the brainstem and cerebellum of 12 (33%) of the 36 victims, while there were none in the control group.…”

Section: Resultssupporting

confidence: 61%

Methemoglobinemia as biomarker and precursor of brain capillary oxidative damage link to ferric iron accumulation and originator of neurodegenerative diseases

Mohorović¹,

Lavezzi²,

Jonjić³

et al. 2017

J Syst Integr Neurosci

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Our main aim is to make a contribution to the establishment of sources of oxidants as the key factors in understanding the role that oxidants and oxidative stress play in the pathogenesis of neurodegeneration, i.e. in the progression of Alzheimer's disease (AD). Our original observation pointed out the main difference between the hemoglobin and methemoglobin degradation, did from the heme oxygenation when a hemoglobin results in ferrous (Fe2+) iron, but methemoglobin catabolism produces ferric (Fe3+) iron. The methemoglobin plays a role of the carrier, the donor of cytotoxic and redox-active ferric (Fe3+) iron, and it also acts as the originator of neurodegenerative diseases. The abundant and permanent source of redox-active ferric (Fe3+) iron which, without Ferrous-Ferric inversions, has "in situ" direct impact on endothelial small vessels in the brain accumulates and increases the rate of capillary endothelial cell apoptosis and possibly crosses into brain parenchyma to the astrocytes, glia, neurons, and other neuronal cells. Our understanding of the transport and neuronal accumulation of ferric (Fe3+) iron points to how microvessels are organized into a well-structured neurovascular unit with harmful consequences to the brain. Our previously conducted research found that the neonatal jaundice incidence (p=0.034), heart murmur at a later age (p=0.011) and mild disorders in children and adults such as dyslalia and learning/memory impairments (p=0.002) were significantly higher than in children and adults of control mothers without pregnancy methemoglobinemia.The consequence are performed as initial brain iron harmful effects from the mother-fetal pregnancy methemoglobinemia complication, and according to our hypothesis in humans could be followed with the neuronal death, the disease aging process, and leading finally to the severe disorders as AD, PD and other neurodegenerative diseases.

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Section: Resultssupporting

confidence: 61%

Methemoglobinemia as biomarker and precursor of brain capillary oxidative damage link to ferric iron accumulation and originator of neurodegenerative diseases

Mohorović¹,

Lavezzi²,

Jonjić³

et al. 2017

J Syst Integr Neurosci

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“…Obtained proper research found an incidence of neonatal jaundice (p = 0.034), heart murmur at a later age (p = 0.011), as well as child and adult mild disorders such as dyslalia and learning/memory impairments (p = 0.002) significantly higher than in the children and adults of control mothers without pregnancy methemoglobinemia [12]. Lavezzi, Mohorovic et al recently presented findings, confirmed by pathohistological techniques, that under adverse conditions, ferric iron positivity in capillary endothelial cells of the BBB in the fetus rises, also resulting in preterm birth, stillbirth or early neonatal death [13]. The application of the Blue Prussian method highlighted accumulations of blue gra-nulations, indicative of nonheme Fe 3+ -positive reactions in the brainstem and cerebellum of 12 (33%) of the 36 sudden intrauterine unexplained death (SIUD) and sudden infant death syndrome (SIDS) victims and in none of the control group.…”

Section: Methods and Resultsmentioning

confidence: 58%

“…The positivity of free iron in the cerebral parenchyma of a patient with Alzheimer's disease is represented in Figure 6. In the same cases of their previous study [13], Lavezzi, Mohorovic et al, by applying the TUNEL method, highlighted in the same cases showing iron deposition in the capillary endothelial cells of the BBB and in the brain parenchima, high percentages of apoptotic cells in the ventricular barriers, and precisely in the ependyma and in choroid plexus epithelial cells (Figures 7 and 8). …”

Section: Methods and Resultsmentioning

confidence: 60%

Methemoglobinemia—A biomarker and a link to ferric iron accumulation in Alzheimer’s disease

Mohorović¹,

Lavezzi²,

Štifter³

et al. 2014

ABB

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Understanding the mechanism of oxidative stress is likely to yield new insights regarding the pathogenesis of Alzheimer's disease (AD). Our earlier work focused on the difference between hemoglobin and methemoglobin degradation, respectively leading to ferrous (Fe 2+ ) iron, or ferric (Fe 3+ ) iron. Methemoglobin has the role of carrier, the donor of cytotoxic and redox-active ferric (Fe 3+ ) iron, which can directly accumulate and increase the rate of capillary endothelial cell apoptosis, and may cross into the brain parenchyma, to the astrocytes, glia, neurons, and other neuronal cells (neurovascular unit). This supposition helps us to understand the transport and neuronal accumulation process of ferric iron, and determine how iron is transported and accumulated intracellularly, identifiable as "Brain rust". Earlier research found that the incidences of neonatal jaundice (p = 0.034), heart murmur (p = 0.011) and disorders such as dyslalia and learning/memory impairments (p = 0.002) were significantly higher in those children born from mothers with methemoglobinemia. Our hypothesis suggests that prenatal iron abnormalities could lead to greater neuronal death, the disease ageing process, and neurodegenerative disorders such as AD and other neurodegenerative diseases. KEYWORDS

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“…Other staining materials are Lillie for the neuromelanin pigment (28) and Perl’s Prussian blue for iron in oxygen-transporting heme mechanism (29). …”

Section: Stepwise Proceduresmentioning

confidence: 99%

Updates on the Methodological Approaches for Carrying Out an In-Depth Study of the Cardiac Conduction System and the Autonomic Nervous System of Victims of Sudden Unexplained Fetal and Infant Death

Alfonsi

Crippa

2016

Front. Med.

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This article contains a set of protocols for histopathological techniques that can be used for carrying out in-depth studies of cases of sudden infant death syndrome and sudden intrauterine unexplained fetal death syndrome. In order to enable researchers to advance hypotheses regarding the causes of the unexpected death of infants and fetuses, the authors propose three innovative and accurate methodologies for studying the cardiac conduction system, the peripheral cardiac nervous system, and the central autonomic nervous system. Over the years, these protocols have been developed, modified, and improved on a vast number of cases which has enabled pathologists to carry out the microscopic analyses of the structures which regulate life, in order to highlight all the possible morphological substrates of pathophysiological mechanisms that may underlie these syndromes.In memory of our research professor Lino Rossi (1923–2004).

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Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia

Cited by 15 publications

References 51 publications

Methemoglobinemia as biomarker and precursor of brain capillary oxidative damage link to ferric iron accumulation and originator of neurodegenerative diseases

Methemoglobinemia as biomarker and precursor of brain capillary oxidative damage link to ferric iron accumulation and originator of neurodegenerative diseases

Methemoglobinemia—A biomarker and a link to ferric iron accumulation in Alzheimer’s disease

Updates on the Methodological Approaches for Carrying Out an In-Depth Study of the Cardiac Conduction System and the Autonomic Nervous System of Victims of Sudden Unexplained Fetal and Infant Death

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