Increasing epidemiological and experimental evidence implicates gestational infections as one important factor involved in the pathogenesis of several neuropsychiatric disorders. Corresponding preclinical model systems based upon maternal immune activation (MIA) by treatment of the pregnant female have been developed. These MIA animal model systems have been successfully used in basic and translational research approaches, contributing to the investigation of the underlying pathophysiological mechanisms at the molecular, cellular and behavioral levels. The present article focuses on the application of a specific MIA rodent paradigm, based upon treatment of the gestating dam with the viral mimic polyinosinic-polycytidilic acid (Poly(I:C)), a synthetic analog of double-stranded RNA (dsRNA) which activates the Toll-like receptor 3 (TLR3) pathway. Important advantages and constraints of this animal model will be discussed, specifically in light of gestational infection as one vulnerability factor contributing to the complex etiology of mood and psychotic disorders, which are likely the result of intricate multi-level gene×environment interactions. Improving our currently incomplete understanding of the molecular pathomechanistic principles underlying these disorders is a prerequisite for the development of alternative therapeutic approaches which are critically needed in light of the important drawbacks and limitations of currently available pharmacological treatment options regarding efficacy and side effects. The particular relevance of the Poly(I:C) MIA model for the discovery of novel drug targets for symptomatic and preventive therapeutic strategies in mood and psychotic disorders is highlighted in this review article.

The impaired infection control related to the functional immaturity of the neonatal immune system is an important cause of infection in preterm newbo

Background: A new mode of surfactant administration without intubation - less invasive surfactant administration (LISA) - has recently been described for premature infants. Objective: We report single-center outcome data of extremely premature infants who have been managed by LISA in our department. Mortality and morbidity rates of the cohort were compared to historical controls from our own center and to data of the Vermont-Oxford Neonatal Network (VONN). Patients and Methods: All infants born at 23-27 weeks' gestational age during 01/2009 and 06/2011 (n = 224) were managed by LISA and included in the study group. Results: LISA was tolerated by 94% of all infants. 68% of infants stayed on continuous positive airway pressure on day 3. The rate of mechanical ventilation was 35% within the first week and 59% during the entire hospital stay. Compared to historical controls, we found significantly higher survival rates (75.8 vs. 64.1%) and significantly less intraventricular hemorrhage (IVH) (28.1 vs. 45.9%), severe IVH (13.1 vs. 23.9%) and cystic periventricular leukomalacia (1.2 vs. 5.6%); only persistent ductus arteriousus (PDA) (74.7 vs. 52.6%) and retinopathy of prematurity (ROP) (40.5 vs. 21.1%) occurred significantly more often. Compared to VONN data, we found significantly less chronic lung disease (20.6 vs. 46.4%), severe cerebral lesions (IVH 3/4 + cystic PVL; 9.4 vs. 16.1%) and ROP (all grades) (40.5 vs. 56.5%); only PDA (74.7 vs. 63.1%) and severe ROP (> grade 2) (24.1 vs. 14.1%) occurred significantly more often in our cohort. Conclusion: Surfactant can be effectively and safely delivered via LISA and this is associated with low rates of mechanical ventilation and various adverse outcomes in extremely premature infants.

Gestational infection is increasingly being recognized for its involvement as causative mechanism in severe developmental brain abnormalities and its contribution to the pathogenesis of psychopathologies later in life. First observations in the widely accepted maternal immune activation (MIA) model based upon the systemic administration of the viral mimetic Polyinosinic:polycytidylic acid (poly(I:C)) have recently suggested a transmission of behavioral and transcriptional traits across generations. Although maternal care behavior (MCB) is known as essential mediator of the transgenerational effects of environmental challenges on offspring brain function and behavior, the possible propagation of alterations of MCB resulting from MIA to following generations has not yet been examined. Here we show that poly(I:C) stimulation at embryonic day 12.5 (E12.5) leads to aberrant MCB and that this effect is transmitted to the female F1 offspring. The transgenerational effects on MCB are paralleled by enhanced depression-like behavior in the second generation F2 offspring with contributions of both maternal and paternal heritages. Examination of offspring hippocampal expression of genes known as targets of MCB and relevant for ensuing non-genetic transmission of altered brain function and behavior revealed transgenerationally conserved and modified expressional patterns in the F1 and F2 generation. Collectively these data firstly demonstrate the transgenerational transmission of the impact of gestational immune activation on the reproductive care behavior of the mother. Behavioral and molecular characteristics of first and second generation offspring suggest transgenerationally imprinted consequences of gestational infection on psychopathological traits related to mood disorders which remain to be examined in future cross-fostering experiments.

Specific probiotics prevent necrotizing enterocolitis (NEC). A mixture of lactobacilli and bifidobacteria (Infloran) was highly effective in Asian very-low-birth-weight (VLBW) infants. We analyzed the effect of Infloran on NEC, NEC severity, and the influence of enteral feedings (breast milk vs. formula) on NEC prevention in a cohort of European VLBW infants. Infloran was implemented for routine use at our department. VLBW infants receiving probiotics were prospectively followed (2010–2012) and compared with historic controls (2008–2009). Data on NEC, neonatal morbidity, feeding tolerance, and descriptive parameters on NEC cases were analyzed. Infloran had no statistically significant impact on NEC (controls: 24/233 (10.3%); probiotics: 16/230 (7%); P = 0.2). However, NEC was significantly reduced in infants of the probiotics group who were fed any breast milk (20/179 (11.2%) vs. 10/183 (5.5%); P = 0.027), whereas it was ineffective in infants exclusively fed formula (4/54 (7.4%) vs. 6/44 (13.6%); P = 0.345). Occurrence of severe NEC (IIIb), time until full feeds, and gastric residuals were similar. Infloran was of lower efficacy in a European VLBW cohort and showed a reduction of NEC only in infants fed breast milk. Future studies should investigate the influence of feeding formula or breast milk on the effect of probiotics.