Functional Connectivity and Metabolic Alterations in Medial Prefrontal Cortex in a Rat Model of Fetal Alcohol Spectrum Disorder: A Resting-State Functional Magnetic Resonance Imaging and in vivo Proton Magnetic Resonance Spectroscopy Study
In this study, we analyzed the functional connectivity and neurochemical levels of the prefrontal cortex (PFC) using resting-state functional magnetic resonance imaging (rsfMRI) and proton magnetic resonance spectroscopy (1H-MRS) in ethanol-exposed (Eth) and control (Ctr) rats. Pregnant Long-Evans rats were fed a liquid diet containing ethanol (2.1 –6.46% v/v ethanol) from gestational days 6 to 21 (Eth). Ctr animals received an isocaloric, isonutritive liquid diet. In young adulthood, male and female offspring underwent in vivo MRI using a 7.0-Tesla system.1H-MRS from the PFC and whole brain rsfMRI were obtained on the a...
Source: Developmental Neuroscience - April 18, 2019 Category: Neuroscience Source Type: research

The Arginase Pathway in Neonatal Brain Hypoxia-Ischemia
Brain damage after hypoxia-ischemia (HI) occurs in an age-dependent manner. Neuroprotective strategies assumed to be effective in adults might have deleterious effects in the immature brain. In order to create effective therapies, the complex pathophysiology of HI in the developing brain requires exploring new mechanisms. Critical determinants of neuronal survival after HI are the extent of vascular dysfunction, inflammation, and oxidative stress, followed later by tissue repair. The key enzyme of these processes in the human body is arginase (ARG) that acts via the bioavailability of nitric oxide, and the synthesis of pol...
Source: Developmental Neuroscience - April 18, 2019 Category: Neuroscience Source Type: research

Assessing Cerebral Metabolism in the Immature Rodent: From Extracts to Real-Time Assessments
Brain development is an energy-expensive process. Although glucose is irreplaceable, the developing brain utilizes a variety of substrates such as lactate and the ketone bodies, β-hydroxybutyrate and acetoacetate, to produce energy and synthesize the structural components necessary for cerebral maturation. When oxygen and nutrient supplies to the brain are restricted, as in neonatal hypoxia-ischemia (HI), cerebral energy metabolism undergoes alterations in substrate use to preserve the production of adenosine triphosphate. These changes have been studied by in situ biochemical methods that yielded valuable quantitative in...
Source: Developmental Neuroscience - April 16, 2019 Category: Neuroscience Source Type: research

How Early Can a Seizure Happen? Pathophysiological Considerations of Extremely Premature Infant Brain Development
Seizures in neonates represent a neurologic emergency requiring prompt recognition, determination of etiology, and treatment. Yet, the definition and identification of neonatal seizures remain challenging and controversial, in part due to the unique physiology of brain development at this life stage. These issues are compounded when considering seizures in premature infants, in whom the complexities of brain development may engender different clinical and electrographic seizure features at different points in neuronal maturation. In extremely premature infants (#x3c; 28 weeks gestational age), seizure pathophysiology has n...
Source: Developmental Neuroscience - April 8, 2019 Category: Neuroscience Source Type: research

Chorioamnionitis in Rats Precipitates Extended Postnatal Inflammatory Lymphocyte Hyperreactivity
Preterm birth is an important cause of perinatal brain injury (PBI). Neurological injury in extremely preterm infants often begins in utero with chorioamnionitis (CHORIO) or inflammation/infection of the placenta and concomitant placental insufficiency. Studies in humans have shown dysregulated inflammatory signaling throughout the placental-fetal brain axis and altered peripheral immune responses in children born preterm with cerebral palsy (CP). We hypothesized that peripheral immune responses would be altered in our well-established rat model of CP. Specifically, we proposed that isolated peripheral blood mononuclear ce...
Source: Developmental Neuroscience - March 31, 2019 Category: Neuroscience Source Type: research

Age-Dependent Electrocorticogram Dynamics and Epileptogenic Responsiveness in Rats Subjected to Prenatal Hypoxia
Using electrocorticogram (ECoG) analysis, we compared age-related dynamics of general neuronal activity and convulsive epileptiform responsiveness induced by intracortical microinjections of 4-aminopyridine (4-AP) in control Wistar rats and those subjected to prenatal hypoxia (Hx; E14; 7% O2, 3 h). The studies were carried out in three age periods roughly corresponding to childhood (P20 –27), adolescence (P30–45), and adulthood (P90–120). It was found that in the process of postnatal development of the control rats, the peak of the ECoG power spectrum density (PSD) of the theta rhythm during wakefulness shifted from ...
Source: Developmental Neuroscience - March 22, 2019 Category: Neuroscience Source Type: research

Golgipathies in Neurodevelopment: A New View of Old Defects
The Golgi apparatus (GA) is involved in a whole spectrum of activities, from lipid biosynthesis and membrane secretion to the posttranslational processing and trafficking of most proteins, the control of mitosis, cell polarity, migration and morphogenesis, and diverse processes such as apoptosis, autophagy, and the stress response. In keeping with its versatility, mutations in GA proteins lead to a number of different disorders, including syndromes with multisystem involvement. Intriguingly, however, #x3e; 40% of the GA-related genes known to be associated with disease affect the central or peripheral nervous system, highl...
Source: Developmental Neuroscience - March 15, 2019 Category: Neuroscience Source Type: research

Calbindin-1 Expression in the Hippocampus following Neonatal Hypoxia-Ischemia and Therapeutic Hypothermia and Deficits in Spatial Memory
Hippocampal injury following neonatal hypoxia-ischemia (HI) leads to memory impairments despite therapeutic hypothermia (TH). In the hippocampus, the expression of calbindin-1 (Calb1), a Ca2+-buffering protein, increases during postnatal development and decreases with aging and neurodegenerative disorders. Since persistent Ca2+ dysregulation after HI may lead to ongoing injury, persistent changes in hippocampal expression of Calb1 may contribute to memory impairments after neonatal HI. We hypothesized that, despite TH, neonatal HI persistently decreases Calb1 expression in the hippocampus, a change associated with memory d...
Source: Developmental Neuroscience - March 14, 2019 Category: Neuroscience Source Type: research

Oligodendrocyte Progenitor Cell Proliferation and Fate after White Matter Stroke in Juvenile and Adult Mice
The incidence of stroke in children is 2.4 per 100,000 person-years and results in long-term motor and cognitive disability. In ischemic stroke, white matter (WM) is frequently injured, but is relatively understudied compared to grey matter injury. Previous research suggests that the cellular response to WM ischemic injury is different at different ages. Little is known about whether WM repair mechanisms differ in children and adults. We utilized a model of focal ischemic WM injury to determine the oligodendrocyte (OL) response to focal WM ischemic injury in juvenile and adult mice.Methods: Juvenile (21 –25 days of age) ...
Source: Developmental Neuroscience - March 14, 2019 Category: Neuroscience Source Type: research

Strain-Related Differences in Mouse Neonatal Hypoxia-Ischemia
This study confirms that CD1 mice are more susceptible to injury than C57Bl/6J mice and that strain selection is important when using mouse models of HI.Dev Neurosci (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 7, 2019 Category: Neuroscience Source Type: research

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