Early Brain Activity Relates to Subsequent Brain Growth in Premature Infants

Recent experimental studies have shown that early brain activity is crucial for neuronal survival and the development of brain networks; however, it has been challenging to assess its role in the developing human brain. We employed serial quantitative magnetic resonance imaging to measure the rate of growth in circumscribed brain tissues from preterm to term age, and compared it with measures of electroencephalographic (EEG) activity during the first postnatal days by 2 different methods. EEG metrics of functional activity were computed: EEG signal peak-to-peak amplitude and the occurrence of developmentally important spontaneous activity transients (SATs). We found that an increased brain activity in the first postnatal days correlates with a faster growth of brain structures during subsequent months until term age. Total brain volume, and in particular subcortical gray matter volume, grew faster in babies with less cortical electrical quiescence and with more SAT events. The present findings are compatible with the idea that (1) early cortical network activity is important for brain growth, and that (2) objective measures may be devised to follow early human brain activity in a biologically reasoned way in future research as well as during intensive care treatmen

Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex

Strategies to enhance the capacity of grafted stem/progenitors cells to generate multipotential, proliferative and migrating pools of cells in the postnatal brain could be crucial for structural repair after brain damage. We investigated whether the over-expression of basic fibroblast growth factor 2 (FGF-2) in neural progenitor cells (NPCs) could provide a robust source of migrating NPCs for tissue repair in the rat cerebral cortex. Using live imaging we provide direct evidence that FGF-2 over-expression significantly enhances the migratory capacity of grafted NPCs in complex 3D structures, such as cortical slices. Furthermore, we show that the migratory as well as proliferative properties of FGF-2 over-expressing NPCs are maintained after in vivo transplantation. Importantly, after transplantation into a neonatal ischaemic cortex, FGF-2 over-expressing NPCs efficiently invade the injured cortex and generate an increased pool of immature neurons available for brain repair. Differentiation of progenitor cells into immature neurons was correlated with a gradual down-regulation of the FGF-2 transgene. These results reveal an important role for FGF-2 in regulating NPCs functions when interacting with the host tissue and offer a potential strategy to generate a robust source of migrating and immature progenitors for repairing a neonatal ischaemic corte

Lactoferrin and prematurity: a promising milk protein?

Lactoferrin (Lf) is the major whey protein in milk with multiple beneficial health effects, including direct anti-microbial activities, anti-inflammatory effects and iron homeostasis. Lf oral supplementation in human preterm infants has been shown to reduce the incidence of sepsis and necrotizing enterocolitis. In preclinical models of antenatal stress and perinatal brain injury bovine Lf protected the developing brain from neuronal loss, improved connectivity, increased neurotrophic factors and decreased inflammation. It also supported brain development and cognition. Further, Lf could prevent preterm delivery, through a reduction of pro-inflammatory factors and inhibition of premature cervix maturation. We review here the latest research on lactoferrin in the field of neonatology.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Mild Neonatal Brain Hypoxia-Ischemia in Very Immature Rats Causes Long-Term Behavioral and Cerebellar Abnormalities at Adulthood

Systemic hypoxia-ischemia (HI) often occurs during preterm birth in human. HI induces injuries to hinder brain cells mainly in the ipsilateral forebrain structures. Such HI injuries may cause lifelong disturbances in the distant regions, such as the contralateral side of the cerebellum. We aimed to evaluate behavior associated with the cerebellum, to acquire cerebellar abundant metabolic alterations using in vivo( 1)H magnetic resonance spectroscopy (H-1 MRS), and to determine GFAP, NeuN, and MBP protein expression in the left cerebellum, in adult rats after mild early postnatal HI on the right forebrain at day 3 (PND3). From PND45, HI animals exhibited increased locomotion in the open field while there is neither asymmetrical forelimb use nor coordination deficits in the motor tasks. Despite the fact that metabolic differences between two cerebellar hemispheres were noticeable, a global increase in glutamine of HI rats was observed and became significant in the left cerebellum compared to the sham-operated group. Furthermore, increases in glutamate, glycine, the sum of glutamate and glutamine and total choline, only occurred in the left cerebellum of HI rats. Remarkably, there were decreased expression of MBP and NeuN but no detectable reactive astrogliosis in the contralateral side of the cerebellum of HI rats. Taken together, the detected alterations observed in the left cerebellum of HI rats may reflect disequilibrium in the glutamate-glutamine cycle and a delay in the return of glutamine from astrocytes to neurons from hypoxic-ischemic origin. Our data provides in vivo evidence of long-term changes in the corresponding cerebellum following mild neonatal HI in very immature rats, supporting the notion that systemic HI could cause cell death in the cerebellum, a distant region from the expected injury site

3D remote sensing as a tool for river and riparian area regional monitoring in Wallonia (Belgium)

Sous l’impulsion de son administration, la Wallonie a entamé un processus de révision des modalités de gestion de ses cours d’eau publics, notamment à travers le projet des Programmes d’actions sur les rivières par une approche intégrée et sectorisée (PARIS). Les PARIS ont pour but d’intégrer dans le temps et dans l’espace l’ensemble des mesures de gestion spécifiques au linéaire des cours d’eau en fonction d’enjeux prioritaires identifiés à l’échelle d’unités de gestion homogènes : les secteurs (6 185 secteurs de gestion de 2 km de long en moyenne). La mise en place et le suivi de ces plans de gestion impliquent de facto le développement d’outils de suivi efficaces, permettant d’établir les états des lieux pour la planification des actes de gestion et à terme, d’évaluer l’efficacité desdits plans de gestion. Ces opérations doivent se réaliser sur près de 12 000 km de cours d’eau et de bandes riveraines associées sur une base objective et commune à l’ensemble des gestionnaires des cours d’eau publics. Des données fines de télédétection sont disponibles et acquises de manière régulière par l’administration wallonne ; des solutions dérivées de ces sources de données permettront de répondre partiellement aux besoins réguliers en information des plans de gestion PARIS à un coût réduit. Pour atteindre cet objectif, un protocole a été établi à partir de nuages de points lidar (light detection and ranging ; densité 1 point « sol » par m2) complétés par des nuages de points photogrammétriques. Ces données ont été utilisées afin de caractériser la structure spatiale des bandes riveraines du réseau hydrographique public wallon à partir de six paramètres. Ces paramètres peuvent être d’ordre hydromorphologique (hauteur des berges, largeur et sinuosité du lit mineur), ou décrire la structure des forêts riveraines (hauteur moyenne et continuité longitudinale des peuplements arborés et ombrage du lit mineur). Différentes formes de visualisations de l’information peuvent appuyer le processus décisionnel des gestionnaires, de l’échelle locale (secteurs d’une masse d’eau DCE (directive cadre sur l’eau) à l’échelle régionale (354 masses d’eau DCE). Les paramètres extraits dans le cadre de ce projet seront prochainement intégrés au sein d’une plateforme informatique permettant leur visualisation à différentes échelles ainsi que l’encodage des actions par les gestionnaires.The Walloon administration has initiated a process of reform of river management policies, notably through the project PARIS action programs. The PARIS programs aim the integration in time and space of all specific management measures regarding public waterways based on priority issues identified at the level of homogeneous management units (6185 units, with mean length of 2 km). The implementation and monitoring of these management plans involve the development of effective monitoring tools to establish the initial state, planning acts of management and evaluating the effectiveness of such management plans. These operations must be carried out on nearly 12,000 km of streams and associated riparian area. This task must be realized on an objective and common basis for all of public waterways managers. Fine remote sensing data’s are available and regularly acquired by the Walloon administration. Derived solutions of these data sources will partially meet the information needs of PARIS management plans at reduced cost. To achieve this goal, a protocol has been established based on lidar point clouds (density 1 point «soil»/m2) completed by photogrammetric points clouds. These data were used to characterize the spatial structure of riparian areas associated with all of the Walloon public water system (>12,000 km) through six parameters. These parameters can be hydromorphological (height of banks, width, and sinuosity of the riverbed), or describe the structure of riparian forests (average height, longitudinal continuity, and shading of the riverbed). Different types of visualizations can support management decision-making to the local level (single river management unit) to regional (354 waterbodies of the water framework directive). Through various visualizations at different scales, the extracted parameters by the project will be integrated into a webGIS platform used by the river managers to report and plan their management actions

Delayed cortical impairment following lipopolysaccharide exposure in preterm fetal sheep

Preterm infants exhibit chronic deficits in white matter (WM) and cortical maturation. Although fetal infection/inflammation may contribute to WM pathology, the factors contributing to cortical changes are largely unknown. We examined the effect of fetal lipopolysaccharide (LPS) exposure on WM and cortical development as assessed by magnetic resonance imaging (MRI), electroencephalography (EEG), and histopathology in fetal sheep at preterm human equivalent age

Repetitive Erythropoietin Treatment Improves Long-Term Neurocognitive Outcome by Attenuating Hyperoxia-Induced Hypomyelination in the Developing Brain

Introduction:Preterm infants born before 28 weeks of gestation are at high risk of neurodevelopmental impairment in later life. Cerebral white and gray matter injury is associated with adverse outcomes. High oxygen levels, often unavoidable in neonatal intensive care, have been identified as one of the main contributing factors to preterm brain injury. Thus, preventive and therapeutic strategies against hyperoxia-induced brain injury are needed. Erythropoietin (Epo) is a promising and also neuroprotective candidate due to its clinical use in infants as erythropoiesis-stimulating agent. Objective:The objective of this study was to investigate the effects of repetitive Epo treatment on the cerebral white matter and long-term motor-cognitive outcome in a neonatal rodent model of hyperoxia-induced brain injury. Methods:Three-day old Wistar rats were exposed to hyperoxia (48 h, 80% oxygen). Four doses of Epo (5,000 IU/kg body weight per day) were applied intraperitoneally from P3-P6 with the first dose at the onset of hyperoxia. Oligodendrocyte maturation and myelination were evaluated via immunohistochemistry and Western blot on P11. Motor-cognitive deficits were assessed in a battery of complex behavior tests (Open Field, Novel Object Recognition, Barnes maze) in adolescent and fully adult animals. Following behavior tests animals underwent post-mortem diffusion tensor imaging to investigate long-lasting microstructural alterations of the white matter. Results:Repetitive treatment with Epo significantly improved myelination deficits following neonatal hyperoxia at P11. Behavioral testing revealed attenuated hyperoxia-induced cognitive deficits in Epo-treated adolescent and adult rats. Conclusion:A multiple Epo dosage regimen protects the developing brain against hyperoxia-induced brain injury by improving myelination and long-term cognitive outcome. Though current clinical studies on short-term outcome of Epo-treated prematurely born children contradict our findings, long-term effects up to adulthood are still lacking. Our data support the essential need for long-term follow-up of preterm infants in current clinical trials