Pediatric research
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Neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and increases in the adult after brain injury. In this study, postnatal day 7 (P7) rats underwent right carotid artery ligation followed by 8% O2 exposure for 90 min, a lesioning protocol that resulted in ipsilateral forebrain hypoxic-ischemic (HI) injury. The effects of HI injury on SVZ cell proliferation and neurogenesis were examined 1-3 wk later by morphometric measurement of dorsolateral SVZ size; by immunoassays to detect incorporation of bromodeoxyuridine (BrdU) in proliferating cells; and by immunoassays of doublecortin, a microtubule-associated protein expressed only by immature neurons. ⋯ However, 4 wk after HI injury, in the lesioned striatum, although BrdU/glial fibrillary acidic protein and BrdU/RIP-labeled cells were identified, no BrdU/neuronal nuclear protein double-labeled cells were found. These results suggest that although acute neonatal HI injury stimulates SVZ proliferation and neurogenesis, there is inadequate trophic support for survival of newly generated neurons. Identification of the trophic factors that enhance maturation and survival of immature neurons could provide important clues for improving recovery after neonatal brain injury.
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To evaluate effects of polymyxin B direct hemoperfusion (PMX-DHP) on a neonatal sepsis cecal ligation and perforation (CLP) model, in 24 anesthetized and mechanically ventilated 3-d-old piglets, 16 were assigned to CLP and an arteriovenous extracorporeal circuit from 3 h until 6 h post-CLP, with a PMX-column in PMX-DHP-treated group (8 piglets) and 8 as sham. Plasma lipopolysaccharide (LPS) was measured at before CLP and at 3 and 9 h. Changes in mean systemic blood pressure (mSBP), mean pulmonary blood pressure, serum IL-6, tumor necrosis factor alpha, interferon gamma, and highly mobile group-1 box protein were measured before CLP and at 1, 3, 6, and 9 h. ⋯ IFN-gamma was only detected in the control group at 9 h. Survival times in the PMX-DHP group were longer than in the control. Thus, PMX-DHP improved septic shock in a neonatal septic model.
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Lung deposition of inhaled drugs in ventilated neonates has been studied in models of questionable relevance. With conventional nebulizers, pulmonary deposition has been limited to 1% of the total dose. The objective of this study was to assess lung delivery of aerosols in a model of neonatal ventilation using a conventional and novel electronic micropump nebulizer. ⋯ Duration of delivery was shorter with APN-C than with the two other nebulizers (2 versus 6 and 10 min for the APN-S and the MistyNeb, respectively; p < 0.001). Electronic micropump nebulizers are more efficient to administer aerosols in an animal model of ventilated neonates. Availability of Aerogen's electronic micropump nebulizers offers new opportunities to study clinical efficacy and risks of aerosol therapy in ventilated neonates.
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We recently showed that acidosis is protective during hypoxia and detrimental during reoxygenation. We hypothesized that the detrimental effect of acidosis during reoxygenation was due to a negative effect on mitochondrial function. Human postmitotic NT2-N neurons were exposed to 3 h of hypoxia and glucose deprivation and then reoxygenated for 0, 1, 4, 9, or 21 h. ⋯ Acidosis during reoxygenation, however, had no effect on the activity of either complex IV or complexes II+III. We conclude that acidosis during hypoxia increases neuronal survival and preserves complex IV activity. Acidosis during reoxygenation has an early detrimental effect on metabolic activity, but this is not mediated through an effect on the mitochondrial complexes IV or II+III.
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Moderate hypothermia is consistently neuroprotective after hypoxic-ischemic insults and is the subject of ongoing clinical trials. In pilot studies, we observed rebound seizure activity in one infant during rewarming from a 72-h period of hypothermia. We therefore quantified the development of EEG-defined seizures during rewarming in an experimental paradigm of delayed cooling for cerebral ischemia. ⋯ Individual seizures were typically short (28.8 +/- 5.8 s versus 29.0 +/- 6.8 s in sham cooled; NS), and of modest amplitude (35.9 +/- 2.8 versus 38.8 +/- 3.4 microV; NS). Neuronal loss in the parasagittal cortex was significantly reduced in the cooled group (51 +/- 9% versus 91 +/- 5%; p <0.002) and was not correlated with rebound epileptiform activity. In conclusion, rapid rewarming after a prolonged interval of therapeutic hypothermia can be associated with a transient increase in epileptiform events but does not seem to have significant adverse implications for neural outcome.