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Abstract: Brain injury is an important cause of morbidity in infants at risk for exposure to chronic hypoxia. Using a transgenic mouse that expresses green fluorescent protein (GFP) within this progenitor population we have previously shown that exposure to chronic hypoxia significantly decreases the progenitor stem cell pool in the dentate gyrus of the hippocampus that is in part mediated by inhibition of the mammalian target of rapamycin (mTOR) pathway. Hence we hypothesized that pharmacological inhibition of the mTOR pathway using rapamycin will alter the progenitor stem cell pool and impair the development of the dentate gyrus. We find that prolonged inhibition of the mTOR pathway causes a decrease in the early progenitor stem cell pool, demonstrated by decreased GFP-expressing progenitors, which persists long term. However there is a significant increase in proliferating progenitor cell pool, as seen by increased BrdU that is coupled with increased apoptosis thereby leading to fewer Neu N-expressing mature neurons. Further inhibition of the mTOR pathway leads to depletion of the astrocyte and microglial pool in the dentate gyrus as well. Overall our findings demonstrate that pharmacological inhibition of the mTOR pathway leads to impaired development of the DG, raising the concern that in young children could impair cognitive development. [Copyright &y& Elsevier]

Abstract: Chronic hypoxia (CH) present in infants with cyanotic congenital heart disease may be responsible for subsequent cognitive deficits seen in these children. In a rat model of CH [10% O2 between postnatal day (P) 3 and 28], we have demonstrated significant alterations in energy metabolism and excitatory neurotransmission in the developing hippocampus. These alterations may adversely affect dendritic morphology, which is a highly energy-dependent and excitatory neurotransmitter-mediated event, and hippocampus-mediated behaviors. We measured the apical segment length of dendrites in pyramidal neurons of the CA1 region of the hippocampus using microtubule-associated protein-2 (MAP-2) histochemistry on P28 while the animals were hypoxic (n =8 in CH and n =6 in control), and on P56 after the animals had been normoxic for 4 weeks (n =8/group). We also compared dorsal hippocampus-dependent trace fear conditioning and dorsal hippocampus-independent delay fear conditioning on P56. Developmental trajectory of the apical segment length was similar in CH and controls, decreasing between P28 and P56. However, when compared with the controls, the apical segment length was longer in the CH group on both P28 [55.11±2.30 μm (CH) vs. 40.52±1.20 μm (control), p <0.001] and P56 [44.01±1.56 μm (CH) vs. 31.75±1.31 μm (control), p <0.001], suggesting the persistence of an immature dendritic architecture. Both trace and delay fear conditioning were decreased in the CH group, suggesting functional abnormality beyond the dorsal hippocampus. These structural and functional alterations may contribute to the cognitive deficits seen in infants at risk for CH. [Copyright &y& Elsevier]

Abstract: The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9–11 μl centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myo-inositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios (P &#60; 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia. [Copyright &y& Elsevier]

• Weight gain is due to unhealthy foods rather than engaging in unhealthy activities. • Three year olds do not make a food/activity distinction for height or weight. • Four and 5 year olds think foods primarily cause height and weight differences. • Results suggest that the role of foods tends to predominate in people's conceptions of body size. Despite the important ways that both food and physical activities influence body size, much prior research has focused exclusively on children's concepts of food. The present studies address this issue by comparing preschoolers' (N = 128) and adults' (N = 64) understanding of the causal consequences of different foods and activities on height and weight. Participants were asked to make predictions (Study 1) or provide explanations (Study 2). Three- to 5-year-olds predicted heavier weight more on the basis of unhealthy foods than unhealthy activities, but did not differentiate their predictions about height on the basis of food or activity. We also found that 4- and 5-year-olds, but not 3-year-olds, explained differences in weight and height more on the basis of food than on the basis of activity. Together, these results suggest that children's and adults' strongest links were between unhealthy food and greater weight, suggesting that the role of food tends to predominate in people's conceptions of body size. [ABSTRACT FROM AUTHOR]

Background: Foreign body aspiration (FBA) is a common cause of morbidity and mortality in children < 3 years of age. Guidelines recommend performing a bronchoscopy in any suspected or confirmed FBA. Extracorporeal membrane oxygenation (ECMO) can be used as a rescue mode of support in children with life-threatening FBA for stabilization before, during, and after removal.Case Report: We present a series of children with life-threatening FBA who were placed on ECMO for stabilization before or after FB removal and a review of the literature and the Extracorporeal Life Support Organization database. Foreign bodies were removed without complications, and all patients survived ECMO support and were promptly discharged home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ECMO can be safely used in the stabilization of children with life-threatening FBA before, during, and after bronchoscopic removal. ECMO should be considered in the stabilization of children presenting with FBA to facilitate removal. [ABSTRACT FROM AUTHOR]

Chronic hypoxia (CH), a disease state that accounts for significant morbidity and mortality in pediatrics, occurs in many children during critical periods of hippocampal development and cortical myelination. Hippocampal neurogenesis occurs throughout postnatal life and is important for normal development, thus impairment results in long-term cognitive deficits. Erythropoietin (EPO), a drug commonly known for its role in erythrogenesis, has recently been evaluated in neuroprotection in neonatal injury models and preterm brain injury. However, the effects of EPO therapy on hippocampal neurogenesis and myelination in pediatric CH are unknown. We show that CH decreases hippocampal neurogenesis in a pediatric mouse model. This decrease in early and late progenitors, and actively dividing cells is rescued with EPO treatment. Furthermore, we show that CH during this critical time decreases oligodendrocyte progenitor (OPC) populations in the cortex, leading to defective myelination. However, EPO therapy is only able to rescue the OPC but not the loss of mature myelin. Overall, our findings demonstrate that CH in developing mice has significant effects on hippocampal neurogenesis and OPCs, which can be rescued with EPO treatment. Future studies should confirm the role of this FDA-approved therapy in neuroprotection in at-risk pediatric populations. [ABSTRACT FROM AUTHOR]