Glucocorticosteroids effects on brain development in the preterm infants: a role for microglia?

2021 ◽  
Vol 19 ◽  
Author(s):  
Zinni Manuela ◽  
Pansiot Julien ◽  
Elodie Billion ◽  
Baud Olivier ◽  
Mairesse Jérôme

: Prematurity, observed in 15 million births worldwide each year, is a clinical condition that is a major cause of neonatal mortality and morbidity in short and long term. Preterm infants are at high risk for developing respiratory problems, sepsis, and other morbidities leading to neurodevelopmental impairment and neurobehavioral disorders. Perinatal glucocorticosteroids have been widely used for the prevention and treatment of adverse outcomes linked to prematurity. However, despite their shortterm benefits due to their maturational properties, some clinical trials have shown an association between steroids exposure and abnormal brain development in infants born preterm. Neuroinflammation has emerged as a preeminent factor for brain injury in preterm infants, and the major role of microglia, the brain resident immune cells, has been recently highlighted. Considering the role of microglia in the modulation of brain development, the aim of this review is to summarize the effects of endogenous and exogenous glucocorticosteroids on brain development and discuss the possible role of microglia as a mediator of these effects.

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Francesca Garofoli ◽  
Stefania Longo ◽  
Camilla Pisoni ◽  
Patrizia Accorsi ◽  
Micol Angelini ◽  
...  

Abstract Background Prevention of neurodevelopmental impairment due to preterm birth is a major health challenge. Despite advanced obstetric and neonatal care, to date there are few neuroprotective molecules available. Melatonin has been shown to have anti-oxidant/anti-inflammatory effects and to reduce brain damage, mainly after hypoxic ischemic encephalopathy. The planned study will be the first aiming to evaluate the capacity of melatonin to mitigate brain impairment due to premature birth. Method In our planned prospective, multicenter, double-blind, randomized vs placebo study, we will recruit, within 96 h of birth, 60 preterm newborns with a gestational age ≤ 29 weeks + 6 days; these infants will be randomly allocated to oral melatonin, 3 mg/kg/day, or placebo for 15 days. After the administration period, we will measure plasma levels of malondialdehyde, a lipid peroxidation product considered an early biological marker of melatonin treatment efficacy (primary outcome). At term-equivalent age, we will evaluate neurological status (through cerebral ultrasound, cerebral magnetic resonance imaging, vision and hearing evaluations, clinical neurological assessment, and screening for retinopathy of prematurity) as well as the incidence of bronchodysplasia and sepsis. We will also monitor neurodevelopmental outcome during the first 24 months of corrected age (using the modified Fagan Test of Infant Intelligence at 4–6 months and standardized neurological and developmental assessments at 24 months). Discussion Preterm birth survivors often present long-term neurodevelopmental sequelae, such as motor, learning, social-behavioral, and communication problems. We aim to assess the role of melatonin as a neuroprotectant during the first weeks of extrauterine life, when preterm infants are unable to produce it spontaneously. This approach is based on the supposition that its anti-oxidant mechanism could be useful in preventing neurodevelopmental impairment. Considering the short- and long-term morbidities related to preterm birth, and the financial and social costs of the care of preterm infants, both at birth and over time, we suggest that melatonin administration could lead to considerable saving of resources. This would be the first study addressing the role of melatonin in very low birth weight preterm newborns, and it could provide a basis for further studies on melatonin as a neuroprotection strategy in this vulnerable population. Trial registration ClinicalTrials.gov NCT04235673. Prospectively registered on 22 January 2020.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2944 ◽  
Author(s):  
Isadora Beghetti ◽  
Elena Biagi ◽  
Silvia Martini ◽  
Patrizia Brigidi ◽  
Luigi Corvaglia ◽  
...  

Breastfeeding is considered the gold standard for infants’ nutrition, as mother’s own milk (MOM) provides nutritional and bioactive factors functional to optimal development. Early life microbiome is one of the main contributors to short and long-term infant health status, with the gut microbiota (GM) being the most studied ecosystem. Some human milk (HM) bioactive factors, such as HM prebiotic carbohydrates that select for beneficial bacteria, and the specific human milk microbiota (HMM) are emerging as early mediators in the relationship between the development of GM in early life and clinical outcomes. The beneficial role of HM becomes even more crucial for preterm infants, who are exposed to significant risks of severe infection in early life as well as to adverse short and long-term outcomes. When MOM is unavailable or insufficient, donor human milk (DHM) constitutes the optimal nutritional choice. However, little is known about the specific effect of DHM on preterm GM and its potential functional implication on HMM. The purpose of this narrative review is to summarize recent findings on HMM origin and composition and discuss the role of HMM on infant health and development, with a specific focus on preterm infants.


2018 ◽  
Vol 69 (3) ◽  
pp. 688-692
Author(s):  
Lucian Nita ◽  
Dorin Tarau ◽  
Gheorghe Rogobete ◽  
Simona Nita ◽  
Radu Bertici ◽  
...  

The issue addressed relates to an area of 1891694 ha of which 1183343 ha are agricultural land (62, 56) located in the south-west of Romania and refer to the use of soil chemical and physical properties as an acceptor for certain crop systems, with minimal undesirable effects both for plants to be grown, as well as soil characteristics and groundwater surface quality. It is therefore necessary on a case-by-case basis, measure stoc or rect the acidic reaction by periodic or alkaline calculations, the improvement of plant nutrition conditions through ameliorative fertilization and the application of measures to improve the physical state, sufficient justification for the need to develop short and long term strategies for the protection and conservation of edifying factors and the need to respect the frequency of field and laboratory investigations at all 8x8 km grids of the National Soil-Grounds Monitoring System (organized by I.C.P.A.) and completing it with the relevant pedological and agrochemical studies.


2020 ◽  
Vol 26 (40) ◽  
pp. 5128-5133
Author(s):  
Kate Levenberg ◽  
Wade Edris ◽  
Martha Levine ◽  
Daniel R. George

Epidemiologic studies suggest that the lifetime prevalence of bipolar spectrum disorders ranges from 2.8 to 6.5 percent of the population. To decrease morbidity and mortality associated with disease progression, pharmacologic intervention is indicated for the majority of these patients. While a number of effective treatment regimens exist, many conventional medications have significant side effect profiles that adversely impact patients’ short and long-term well-being. It is thus important to continue advancing and improving therapeutic options available to patients. This paper reviews the limitations of current treatments and examines the chemical compound Linalool, an alcohol found in many plant species, that may serve as an effective mood stabilizer. While relatively little is known about Linalool and bipolar disorder, the compound has been shown to have antiepileptic, anti-inflammatory, anxiolytic, anti-depressive, and neurotrophic effects, with mechanisms that are comparable to current bipolar disorder treatment options.


Author(s):  
Dean Keith Simonton

Although psychologists typically see creativity as an individual-level event, sociologists and cultural anthropologists are more likely to view it as a sociocultural phenomenon. This phenomenon takes place at the level of relatively large and enduring collectives, such as cultures, nations, and even whole civilizations. This chapter reviews the extensive research on such macro-level creativity. The review begins with a historical overview before turning to the cross-sectional research on the creative Ortgeist, a subject that encompasses the factors that influence the relative creativity of both preliterate cultures and entire modern nations. From there the chapter turns to role of the Zeitgeist in affecting the creativity of civilizations across time—the rise and fall of creative activity. This research examines both quantitative and qualitative causes that operate both short- and long-term.


Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 148
Author(s):  
Alessandra Coscia ◽  
Flaminia Bardanzellu ◽  
Elisa Caboni ◽  
Vassilios Fanos ◽  
Diego Giampietro Peroni

In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one’s life, each subject is colonized by a great number of bacteria, which constitute its specific and individual microbiota. Human bacterial colonization starts during fetal life, in opposition to the previous paradigm of the “sterile womb”. Placenta, amniotic fluid, cord blood and fetal tissues each have their own specific microbiota, influenced by maternal health and habits and having a decisive influence on pregnancy outcome and offspring outcome. The maternal microbiota, especially that colonizing the genital system, starts to influence the outcome of pregnancy already before conception, modulating fertility and the success rate of fertilization, even in the case of assisted reproduction techniques. During the perinatal period, neonatal microbiota seems influenced by delivery mode, drug administration and many other conditions. Special attention must be reserved for early neonatal nutrition, because breastfeeding allows the transmission of a specific and unique lactobiome able to modulate and positively affect the neonatal gut microbiota. Our narrative review aims to investigate the currently identified pre- and peri-natal factors influencing neonatal microbiota, before conception, during pregnancy, pre- and post-delivery, since the early microbiota influences the whole life of each subject.


Children ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 276
Author(s):  
Judith Rittenschober-Böhm ◽  
Tanja Habermüller ◽  
Thomas Waldhoer ◽  
Renate Fuiko ◽  
Stefan M. Schulz ◽  
...  

Vaginal colonization with Ureaplasma (U.) spp. has been shown to be associated with adverse pregnancy outcome; however, data on neonatal outcome are scarce. The aim of the study was to investigate whether maternal vaginal colonization with U. spp. in early pregnancy represents a risk factor for adverse short- or long-term outcome of preterm infants. Previously, 4330 pregnant women were enrolled in an observational multicenter study, analyzing the association between vaginal U. spp. colonization and spontaneous preterm birth. U. spp. colonization was diagnosed via PCR analysis from vaginal swabs. For this study, data on short-term outcome were collected from medical records and long-term outcome was examined via Bayley Scales of Infant Development at 24 months adjusted age. Two-hundred-and-thirty-eight children were born <33 weeks gestational age. After exclusion due to asphyxia, malformations, and lost-to-follow-up, data on short-term and long-term outcome were available from 222 and 92 infants, respectively. Results show a significant association between vaginal U. spp. colonization and severe intraventricular hemorrhage (10.4% vs. 2.6%, p = 0.03), retinopathy of prematurity (21.7% vs. 10.3%, p = 0.03), and adverse psychomotor outcome (24.3% vs. 1.8%, OR 13.154, 95%CI 1.6,110.2, p = 0.005). The data suggest an association between vaginal U. spp. colonization in early pregnancy and adverse short- and long-term outcome of very preterm infants.


Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 514
Author(s):  
Tarek Hatoum ◽  
Robert S. Sheldon

Syncope accounts for up to 2% of emergency department visits and results in the hospitalization of 12–86% of patients. There is often a low diagnostic yield, with up to 50% of hospitalized patients being discharged with no clear diagnosis. We will outline a structured approach to the syncope patient in the emergency department, highlighting the evidence supporting the role of clinical judgement and the initial electrocardiogram (ECG) in making the preliminary diagnosis and in safely identifying the patients at low risk of short- and long-term adverse events or admitting the patient if likely to benefit from urgent intervention. Clinical decision tools and additional testing may aid in further stratifying patients and may guide disposition. While hospital admission does not seem to offer additional mortality benefit, the efficient utilization of outpatient testing may provide similar diagnostic yield, preventing unnecessary hospitalizations.


2018 ◽  
Vol 25 (3) ◽  
pp. 208-226 ◽  
Author(s):  
Zahid Padamsey ◽  
William J. Foster ◽  
Nigel J. Emptage

Ca2+ is an essential trigger for most forms of synaptic plasticity. Ca2+ signaling occurs not only by Ca2+ entry via plasma membrane channels but also via Ca2+ signals generated by intracellular organelles. These organelles, by dynamically regulating the spatial and temporal extent of Ca2+ elevations within neurons, play a pivotal role in determining the downstream consequences of neural signaling on synaptic function. Here, we review the role of three major intracellular stores: the endoplasmic reticulum, mitochondria, and acidic Ca2+ stores, such as lysosomes, in neuronal Ca2+ signaling and plasticity. We provide a comprehensive account of how Ca2+ release from these stores regulates short- and long-term plasticity at the pre- and postsynaptic terminals of central synapses.


2021 ◽  
Author(s):  
◽  
Amy O'Connell

<p>Serotonin is an important neurotransmitter that regulates a range of processes within the brain and is implicated in several psychiatric disorders. In addition, serotonin acts as a developmental signal during critical periods of prenatal development, influencing processes such as neuronal proliferation, migration, and synaptogenesis (Gaspar et al., 2003). The serotonin transporter (5- HTT) plays a key role in regulating extracellular serotonin levels and is the main target of selective-serotonin reuptake inhibitors (SSRIs), a class of drugs that have anti-anxiety and anti- depressive activity. SSRIs cause an acute increase in extracellular serotonin and are commonly prescribed as a treatment for depression and anxiety during pregnancy (Tran & Robb, 2015). Given that these drugs alter serotonin transmission and can pass to the developing fetus via the placenta, it is vital that the outcomes of prenatal SSRI exposure are investigated. In humans, a genetic variant of the gene that codes for the 5-HTT (SLC6A4) has been linked to increased risk for developing depression and anxiety (Caspi et al., 2003). The functional consequences of this genetic polymorphism are life-long alterations in 5-HTT activity, resulting in increased extracellular levels of serotonin (Nakamura et al., 2000). Given prenatal SSRI exposure results in a time-locked blockade of 5-HTT during critical periods of development, it follows that alterations in serotonin during development might similarly result in enhanced risk for depression and anxiety later in life. Outcomes in children prenatally exposed to SSRIs are difficult to study due to confounds of pre- existing maternal depression. Therefore, the current thesis presents two experiments that aimed to further investigate the role of altered extracellular serotonin levels during development in an animal model. Experiment one aimed to develop a method of voluntary oral administration of the SSRI fluoxetine to pregnant rat dams. This method was then applied in experiment two to create a time-locked blockade of 5-HTT during critical periods of development in an animal model of life-long 5-HTT blockade. The aim of experiment two was to directly assess the contribution of short- and long-term 5-HTT blockade on anxiety and depression phenotypes in adult male offspring. In addition, maternal behaviour was assessed to determine whether fluoxetine treatment had an influence on mother-pup interactions that could confound results. To test for anxiety and depression phenotypes, the novel affective disorder test (ADT) was used to assess anxiety behaviour and the deficits in anticipatory pleasure indicative of anhedonia. In the current study, fluoxetine treatment did not have an effect on litter outcomes or mother-pup interactions. Crucially, no significant group differences were found indicating that neither short- nor long- term blockade of 5-HTT resulted in increased anxiety- or depressive-like behaviours in the current experiment. However, limitations with methodological design limit the translatability of these results to the broader literature, and validation of the ADT is required before these results can be generalised beyond this thesis.</p>


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