Vera Neubauer

Neuroprotective effects of the sigma-1 receptor ligand PRE-084 against excitotoxic perinatal brain injury in newborn mice.

Excessive glutamate release followed by N-methyl-D-aspartate receptor (NMDAR) activation plays a crucial role in perinatal brain injury. We have previously shown that dextromethorphan, a low-affinity NMDAR antagonist with anti-inflammatory properties, is neuroprotective against neonatal excitotoxic brain injury. Of interest, dextromethorphan is also a sigma-1 receptor (σ1R) agonist. The pharmacologic class of σ1R agonists has yielded propitious results in various animal models of adult central nervous system pathology. In an established neonatal mouse model of excitotoxic brain injury, we evaluated the effect of the selective σ1R agonist 2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate (PRE-084). A single intraperitoneal injection of 0.1 μg/g (low dose) or 10 μg/g (high dose) bodyweight (bw) PRE-084, given 1h after the excitotoxic insult, significantly reduced lesion size in cortical gray matter 24 h and 120 h after the insult. Repetitive injections of 0.1 μg/g PRE-084 proved to be equally effective. PRE-084 treatment resulted in a decrease in cell death indicated by reduced TUNEL positivity and caspase-3 activation. Furthermore, it lowered the number of isolectin B4-positive, activated microglial cells. PRE-084 had no effect on developmental apoptosis in the undamaged brain. In vitro findings in primary hippocampal neurons suggest that PRE-084 treatment provides partial protection against glutamate induced morphological and functional changes. For excitotoxicity as playing a crucial role in the pathogenesis of perinatal brain injury, we demonstrate for the first time that systemic treatment with the highly selective σ1R agonist PRE-084 protects against NMDAR-mediated excitotoxic brain damage.

Poor postnatal head growth in very preterm infants is associated with impaired neurodevelopment outcome.

To examine the association between neurodevelopmental outcome and head circumference (HC) in a cohort of very preterm infants and in this context to investigate the relevance of suboptimal head size.

The effect of sex on outcome of preterm infants - a population-based survey.

Aim:  To provide comprehensive data on potential sex differences in maternal and neonatal characteristics, short‐term morbidity and neurodevelopmental outcome within an entire geographically determined collective of infants born at a gestational age <32 weeks.

Effect of developmental care for very premature infants on neurodevelopmental outcome at 2 years of age

BACKGROUND To determine the effect of developmental care on neurodevelopmental outcome in formerly preterm infants at a corrected age of 2 years. METHODS A prospective phase-lag study was performed at an Austrian neonatal intensive care unit (NICU). From January 2003 to December 2005 (study period of conventional care) and January 2007 to December 2009 (study period of developmental care), we enrolled all infants born in Tyrol at less than 32 weeks of gestation. During this period a total of 261 of 359 preterm infants (participation rate 72.7%) completed the follow-up visit at 2 years of age; there were 124 children in the conventional and 137 in the developmental care group. The association between developmental care and delayed motor or mental development (Bayley Scales of Infant Development II; psychomotor or mental developmental index <85) was analyzed by means of logistic regression analysis at a corrected age of 24 months. RESULTS Children in the developmental care group showed less psychomotor delay than did those in the control group (developmental care group: 16.1%, conventional care group 27.4%; adjusted odds ratio 0.37 [95% confidence interval: 0.19-0.74], P=0.005). Not smoking in pregnancy and higher gestational age were also significant predictors for a better psychomotor outcome at 2 years of age. Regarding cognitive outcome, no significant difference was observed between these two groups. CONCLUSION Our data implicate that developmental care may result in an improved 2-year psychomotor outcome in formerly preterm infants.

Very preterm children are at increased risk of reduced processing speed at 5 years of age, predicted by typical complications of prematurity and prenatal smoking

Very little is known about risk predictors for the development of reduced processing speed, which can cause intellectual problems in later life. This study identified risk predictors at 5 years of age in a population‐based cohort of very preterm infants.

Poor postdischarge head growth is related to a 10% lower intelligence quotient in very preterm infants at the chronological age of five years

This study examined the relationship between head growth and cognitive outcome at the age of five years in preterm infants born at less than 32 weeks of gestation from 2003 to 2009, as previous research has mostly focused on outcomes in toddlers.

Comparing growth charts demonstrated significant deviations between the interpretation of postnatal growth patterns in very preterm infants

This study compared postnatal growth patterns calculated using different reference data in a large cohort of very preterm infants.

Congenital varicella syndrome in a very low birthweight preterm infant

Congenital varicella syndrome (CVS) is a rare but deleterious consequence of primary varicella zoster virus (VZV) infection during pregnancy. Typical CVS stigmata are cerebral abnormalities, eye diseases and segmentally distributed, cicatricial skin lesions. In this paper the authors report on a male preterm infant, born at 30 weeks of gestation, who developed pustular skin lesions at the age of 4 weeks. The mother had suffered from chickenpox at 14 weeks of gestation. Apart from skin manifestations, critical bronchopulmonary dysplasia made the infant conspicuous. The VZV genome was detected in blood, respiratory secretions and skin lesions. At age 10 weeks he presented with extensive intestinal wall perforation, considered to be related to CVS, which finally led to death. This case shows for the first time the clinical course of CVS in a preterm infant. It illustrates the need for discussion of comprehensive VZV vaccination for seronegative women of childbearing age.

Need for quality control for aEEG monitoring of the preterm infant: a 2-year experience.

Aim:  To establish and apply a questionnaire for the evaluation of amplitude‐integrated electroencephalogram (aEEG) with respect to practicability and feasibility in the NICU, to reveal strategies for improvements in daily use and to investigate the level of staff know‐how with regard to performance and evaluation of bedside aEEG for the purpose of quality control.

Delayed application of the haematopoietic growth factors G-CSF/SCF and FL reduces neonatal excitotoxic brain injury

BACKGROUND Developmental brain injury results in cognitive and motor deficits in the preterm infant. Enhanced glutamate release and subsequent receptor activation are major pathogenetic factors. The effect of haematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF) and flt-3 ligand (FL) on neonatal brain injury is controversially discussed. Timing of treatment is known to be a crucial factor. Based on the hypothesis that an exacerbation of injury is caused by administration of substances in the acute phase, the objective of this study was to evaluate the effect of delayed administration of G-CSF/SCF and FL to protect against excitotoxic brain injury in vivo. METHODS In an established neonatal mouse model of excitotoxic brain injury, we evaluated the effect of daily intraperitoneal doses of G-CSF/SCF or FL, starting 60 h after the excitotoxic insult. RESULTS Intraperitoneal injections of G-CSF/SCF and FL, given 60 h after the excitotoxic insult, significantly reduced lesion size at postnatal days 10, 18 and 90. G-CSF/SCF treatment resulted in a decrease in apoptotic cell death indicated by reduced caspase-3 activation. G-CSF/SCF and FL treatment did not affect apoptosis-inducing factor-dependent apoptosis or cell proliferation. CONCLUSION We show that delayed systemic treatment with the haematopoietic growth factors G-CSF/SCF and FL protects against N-methyl-D-aspartate receptor-mediated developmental excitotoxic brain damage. Our results suggest that neuroprotective effects in this neonatal animal model of excitotoxic brain injury depend on the timing of drug administration after the insult.