The Impact of Toxins on the Developing Brain

Children in care, who have been maltreated, consistently demonstrate poorer educational outcomes than their peers. A number of reasons have been suggested for this such as a lack of stability and opportunities, as compared to their peers. One possible contributor to the poorer educational attainment of children in care is their underlying cognitive vulnerabilities. Cognitive deficits in maltreated children are thought to arise as a result of the impact of trauma on the developing brain. These cognitive deficits include difficulties with executive functioning. Executive functioning abilities include the ability to inhibit behaviour, plan ahead and switch from task to task and are critical for navigating the day to day requirements of educational settings. This article summarises what we know about the cognitive vulnerabilities of maltreated children in care and outlines the implications of these cognitive deficits for supporting maltreated children.

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Early Life Febrile Seizures Impair Hippocampal Synaptic Plasticity in Young Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22158218 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8218

Author(s):

Tatyana Y. Postnikova ◽

Alexandra V. Griflyuk ◽

Dmitry V. Amakhin ◽

Anna A. Kovalenko ◽

Elena B. Soboleva ◽

...

Keyword(s):

Early Life ◽

Significant Risk ◽

Febrile Seizures ◽

Long Term Potentiation ◽

Developing Brain ◽

Functional Impairments ◽

Glycine Site ◽

Functional Changes ◽

Young Rats ◽

The Impact

Febrile seizures (FSs) in early life are significant risk factors of neurological disorders and cognitive impairment in later life. However, existing data about the impact of FSs on the developing brain are conflicting. We aimed to investigate morphological and functional changes in the hippocampus of young rats exposed to hyperthermia-induced seizures at postnatal day 10. We found that FSs led to a slight morphological disturbance. The cell numbers decreased by 10% in the CA1 and hilus but did not reduce in the CA3 or dentate gyrus areas. In contrast, functional impairments were robust. Long-term potentiation (LTP) in CA3-CA1 synapses was strongly reduced, which we attribute to the insufficient activity of N-methyl-D-aspartate receptors (NMDARs). Using whole-cell recordings, we found higher desensitization of NMDAR currents in the FS group. Since the desensitization of NMDARs depends on subunit composition, we analyzed NMDAR current decays and gene expression of subunits, which revealed no differences between control and FS rats. We suggest that an increased desensitization is due to insufficient activation of the glycine site of NMDARs, as the application of D-serine, the glycine site agonist, allows the restoration of LTP to a control value. Our results reveal a new molecular mechanism of FS impact on the developing brain.

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Partial protective effects of melatonin on developing brain in a rat model of chorioamnionitis

Scientific Reports ◽

10.1038/s41598-021-01746-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Geraldine Favrais ◽

Elie Saliba ◽

Léa Savary ◽

Sylvie Bodard ◽

Zuhal Gulhan ◽

...

Keyword(s):

Infectious Agent ◽

Gabaergic Neurons ◽

Developing Brain ◽

Maturation Stage ◽

Protective Effects ◽

Neuroprotective Effects ◽

Candidate Drug ◽

Extremely Preterm ◽

Anti Oxidant ◽

The Impact

AbstractMelatonin has shown promising neuroprotective effects due to its anti-oxidant, anti-inflammatory and anti-apoptotic properties, making it a candidate drug for translation to humans in conditions that compromise the developing brain. Our study aimed to explore the impact of prenatal melatonin in an inflammatory/infectious context on GABAergic neurons and on oligodendrocytes (OLs), key cells involved in the encephalopathy of prematurity. An inflammatory/infectious agent (LPS, 300 μg/kg) was injected intraperitoneally (i.p.) to pregnant Wistar rats at gestational day 19 and 20. Melatonin (5 mg/kg) was injected i.p. following the same schedule. Immunostainings focusing on GABAergic neurons, OL lineage and myelination were performed on pup brain sections. Melatonin succeeded in preventing the LPS-induced decrease of GABAergic neurons within the retrospenial cortex, and sustainably promoted GABAergic neurons within the dentate gyrus in the inflammatory/infectious context. However, melatonin did not effectively prevent the LPS-induced alterations on OLs and myelination. Therefore, we demonstrated that melatonin partially prevented the deleterious effects of LPS according to the cell type. The timing of exposure related to the cell maturation stage is likely to be critical to achieve an efficient action of melatonin. Furthermore, it can be speculated that melatonin exerts a modest protective effect on extremely preterm infant brains.

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Prenatal Glucocorticoid-Exposed Infants Do Not Show an Age-Typical Fear Bias at 8 Months of Age – Preliminary Findings From the FinnBrain Birth Cohort Study

Frontiers in Psychology ◽

10.3389/fpsyg.2021.655654 ◽

2021 ◽

Vol 12 ◽

Author(s):

Eeva-Leena Kataja ◽

Ana João Rodrigues ◽

Noora M. Scheinin ◽

Saara Nolvi ◽

Riikka Korja ◽

...

Keyword(s):

Cohort Study ◽

Birth Cohort ◽

Emotional Processing ◽

Fetal Lung ◽

Developing Brain ◽

Birth Cohort Study ◽

Lung Maturation ◽

Fearful Faces ◽

Postnatal Depressive Symptoms ◽

The Impact

Synthetic glucocorticoids (sGC) are frequently administered to pregnant women at risk for preterm delivery to promote fetal lung maturation. Despite their undeniable beneficial effects in lung maturation, the impact of these hormones on developing brain is less clear. Recent human studies suggest that emotional and behavioral disorders are more common among sGC-exposed vs. non-exposed children, but the literature is sparse and controversial. We investigated if prenatal sGC exposure altered fear bias, a well-established infant attention phenotype, at 8-months. We used eye tracking and an overlap paradigm with control, neutral, happy, and fearful faces, and salient distractors, to evaluate infants’ attention disengagement from faces, and specifically from fearful vs. neutral and happy faces (i.e., a fear bias) in a sample (N = 363) of general population from the FinnBrain Birth Cohort Study. sGC exposed infants (N = 12) did not differ from non-exposed infants (N = 351) in their overall probability of disengagement in any single stimulus condition. However, in comparison with non-exposed infants, they did not show the age-typical fear bias and this association remained after controlling for confounding factors such as prematurity, gestational age at birth, birth weight, sex, and maternal postnatal depressive symptoms. Prenatal sGC exposure may alter emotional processing in infants. The atypical emotion processing in turn may be a predictor of emotional problems later in development. Future longitudinal studies are needed in order to evaluate the long-term consequences of sGC exposure for the developing brain.

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Association of the development of bone metastases with the development of brain metastases in patients with non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e13030 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e13030-e13030

Author(s):

Mohamed Salem ◽

Paul Elson ◽

Nathan A. Pennell ◽

Ammar Sukari ◽

Sherif El-Refai ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Bone Metastases ◽

Cell Lung Cancer ◽

Bone Disease ◽

Small Cell ◽

Developing Brain ◽

Small Cell Lung ◽

The Impact

e13030 Background: In patients (pts) with non-small cell lung cancer (NSCLC), it is unknown whether pts with bone metastases are predisposed to the development of brain metastases. The impact of bevacizumab (Bev) on the development of bone and brain metastases is not fully characterized. Methods: Retrospective review of pts with stage IV NSCLC without brain metastasis at diagnosis was undertaken. The primary endpoint was to determine whether the development of bone metastases is predictive of the development of brain metastases. Secondary endpoints involved the proportion of pts who developed brain and/or bone metastases while being treated with Bev. Data were analyzed using competing risks methods. Results: A total of 175 pts (52% males, median (range) age: 60 y (35-80)) were studied. Of whom 79% received Bev and 21% did not receive Bev as part of their treatment. Overall 34% of pts had bone metastases at the start of therapy. Pts with pre-existing bone metastases tended to develop new bone disease more frequently than pts who did not initially have bone metastases (39% vs. 19%, p =. 01). The incidence of the development of brain metastases among pts who had pre-existing bone metastases was 17% vs.16 % in pts without pre-existing bone metastases. However, the incidence of brain metastases among pts with pre-existing bone disease who developed new bone metastases was 33% vs. 6% in pts who did not develop new bone disease but had pre-existing bone metastases. Adjusting for initial bone disease, development of new bone metastases was associated with a shorter brain metastases-free interval HR 5.06 (2.03-12.65; p = 0.005). In a subgroup analysis based on Bev exposure, the likelihood of developing brain and bone metastases within 2 years of starting Bev was estimated to be 25% and 27%, respectively, while the likelihood of developing brain and bone metastases without Bev treatment was 33% and 43 %, respectively. Conclusions: In pts with NSCLC, the development of new bone metastases may be indicative of the subsequent development of brain metastases. Additionally, Bev therapy may have an effect on the development of both bone and brain metastases. A prospective investigation may be warranted.

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