Ferroptosis and Brain Injury
Ferroptosis is a nonapoptotic form of cell death characterized by the iron-dependent accumulation of toxic lipid reactive oxygen species. Small-molecule screening and subsequent optimization have yielded potent and specific activators and inhibitors of this process. These compounds have been employed to dissect the lethal mechanism and implicate this process in pathological cell death events observed in many tissues, including the brain. Indeed, ferroptosis is emerging as an important mechanism of cell death during stroke, intracerebral hemorrhage, and other acute brain injuries, and may also play a role in certain degener...
Source: Developmental Neuroscience - March 7, 2019 Category: Neuroscience Source Type: research
Seizure Susceptibility Correlates with Brain Injury in Male Mice Treated with Hypothermia after Neonatal Hypoxia-Ischemia
Hypoxic-ischemic encephalopathy is a common neonatal brain injury associated with significant morbidity and mortality despite the administration of therapeutic hypothermia (TH). Neonatal seizures and subsequent chronic epilepsy are frequent in this patient population and current treatments are partially effective. We used a neonatal murine hypoxia-ischemia (HI) model to test whether the severity of hippocampal and cortical injury predicts seizure susceptibility 8 days after HI and whether TH mitigates this susceptibility. HI at postnatal day 10 (P10) caused hippocampal injury not mitigated by TH in male or female pups. TH ...
Source: Developmental Neuroscience - March 7, 2019 Category: Neuroscience Source Type: research
HIF1 α Signaling in the Endogenous Protective Responses after Neonatal Brain Hypoxia-Ischemia
This study confirms the role of neuronal HIF1α signaling in the endogenous protective responses following HI in the developing brain.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 7, 2019 Category: Neuroscience Source Type: research
The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs
Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVCSal,n = 4; UVCBM,n = 6) were humanely killed without intervention; ventilated lambs (VentSal,n = 5; VentBM,n = 7) were...
Source: Developmental Neuroscience - March 7, 2019 Category: Neuroscience Source Type: research
Perinatal High-Fat Diet and Bisphenol A: Effects on Behavior and Gene Expression in the Medial Prefrontal Cortex
Both high-fat diets (HFD) and bisphenol A (BPA), an environmental endocrine disruptor, are prevalent in industrialized societies. Previous studies have detected separate effects of BPA and HFD; however, none have assessed possible interactive effects. Here, pregnant dams consumed 0, 40, or 400 µg BPA/kg/day and were fed either a control (CON; 15.8% kcal fat) or HFD (45% kcal fat) from gestational day 2 through parturition. The pups were individually dosed with BPA from postnatal days (P) 1–10, while the dams continued to consume one of the two diets. Maternal behavior increased with th e HFD while the offspring’s peri...
Source: Developmental Neuroscience - December 21, 2018 Category: Neuroscience Source Type: research
Repeated Pediatric Concussions Evoke Long-Term Oligodendrocyte and White Matter Microstructural Dysregulation Distant from the Injury
Concussion or mild traumatic brain injury (mTBI) is often accompanied by long-term behavioral and neuropsychological deficits. Emerging data suggest that these deficits can be exacerbated following repeated injuries. However, despite the overwhelming prevalence of mTBI in children due to falls and sports-related activities, the effects of mTBI on white matter (WM) structure and its development in children have not been extensively examined. Moreover, the effect of repeated mTBI (rmTBI) on developing WM has not yet been studied, despite the possibility of exacerbated outcomes with repeat injuries. To address this knowledge ...
Source: Developmental Neuroscience - November 22, 2018 Category: Neuroscience Source Type: research
Intrauterine Growth Restriction and Hyperoxia as a Cause of White Matter Injury
Intrauterine growth restriction (IUGR) is estimated to occur in 5% of pregnancies, with placental insufficiency being the most common cause in developed countries. While it is known that white matter injury occurs in premature infants, the extent of IUGR on white matter injury is less defined in term infants. We used a novel murine model that utilizes a thromboxane A2 (TXA2) analog (U46619), a potent vasoconstrictor, to induce maternal hypertension and mimic human placental insufficiency-induced IUGR to study the white matter. We also investigated the role of hyperoxia as an additional risk factor for white matter injury, ...
Source: Developmental Neuroscience - November 14, 2018 Category: Neuroscience Source Type: research
Infants Uniquely Express High Levels of RBM3 and Other Cold-Adaptive Neuroprotectant Proteins in the Human Brain
Neuroprotective cold-shock proteins (CSPs) are abundant in the normothermic neonatal rodent brain but decrease with advancing neurodevelopmental age and are low or absent in the adult brain. It has not been established if neurodevelopmental age alters the baseline expression of CSPs in the human brain. Here, we tested the hypothesis that protein levels of RNA-binding motif 3 (RBM3), reticulon-3 (RTN3), and cold-induced RNA-binding protein (CIRBP) are abundant in the normothermic developing human brain but low-to-absent in adults. We also tested if β-klotho (KLB) is expressed in the developing brain; KLB functions as a cor...
Source: Developmental Neuroscience - November 7, 2018 Category: Neuroscience Source Type: research
NFAT5 Has a Job in the Brain
This article aims to summarize the current knowledge regarding the expression of NFAT5, its regulation of activation, and varied biological functions in the brain.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - November 2, 2018 Category: Neuroscience Source Type: research
Can Functional Polymorphisms in < b > < i > VEGF < /i > < /b > and < b > < i > MMP < /i > < /b > Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?
Conclusion: This study demonstrated that the GA/AA genotype inVEGF RS1570360 and the AA/AC genotype inVEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examineVEGF polymorphisms in association with IVH.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - November 2, 2018 Category: Neuroscience Source Type: research
< b > < i > c-Jun N-Terminal Kinase < /i > < /b > Inhibition Induces Mitochondrial Oxidative Stress and Decreases Survival in Human Neural Stem Progenitors
Neural stem cells are attracting enormous attention in regenerative medicine due to their ability to self-renew and differentiate into the cell lineages that constitute the central nervous system. However, little is known about the mechanism underlying the regulation of their redox environment, which is essential for homeostatic cellular functions. The redox-modulatedc-Jun N-terminal kinases (JNK) are a molecular switch in stress signal transduction and are involved in numerous brain functions. Using a selective but broad-spectrum inhibitor of JNK 1/2/3, we investigated the role of JNK in regulating the levels of reactive ...
Source: Developmental Neuroscience - October 18, 2018 Category: Neuroscience Source Type: research
Brain Diffusion Imaging and Tractography to Distinguish Clinical Severity of Human < b > < i > PLP1 < /i > < /b > -Related Disorders
Aims: We performed quantitative diffusion tensor imaging and brain tractography to distinguish clinical severity in a series of 35 patients with hypomyelinatingPLP1-related disorders classified using the Motor Developmental Score according to the best motor function acquired before the age of 5 years and the gross motor function measure (GMFM) at the time of magnetic resonance imaging acquisition.Methods: We calculated fractional anisotropy and diffusivity values in 26 regions of interest and the numbers of fibers and volumes of hemisphere tractograms. Fiber bundles on tractograms were characterized according to 3 criteria...
Source: Developmental Neuroscience - October 4, 2018 Category: Neuroscience Source Type: research
Biochemical and Morphological Characterization of a Neurodevelopmental Disorder-Related Mono-ADP-Ribosylhydrolase, MACRO Domain Containing 2
In this study, we generated a specific antibody against MacroD2, and carried out expression and morphological analyses of the molecule during mouse brain development. In Western blotting, 2 MacroD2 isoforms with molecular masses of ∼70 and ∼75 kDa started to be expressed at embryonic day 16.5, reached the maximal level at postnatal day 8, and then gradually decreased through P30. In contrast, other isoforms with molecular masses of ∼110 and ∼140 kDa gradually increased during embryonic to postnatal development. In immu nohistochemical analyses, MacroD2 was strongly detected in cortical neurons in layer II–V at P0...
Source: Developmental Neuroscience - September 18, 2018 Category: Neuroscience Source Type: research
Validation of Raised Cord Blood Interleukin-16 in Perinatal Asphyxia and Neonatal Hypoxic-Ischaemic Encephalopathy in the BiHiVE2 Cohort
This study validates findings that cord blood-based IL-16 levels are increased in infants with PA, including those who go on to develop HIE.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - September 11, 2018 Category: Neuroscience Source Type: research
Erratum
Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - September 7, 2018 Category: Neuroscience Source Type: research
