Aims: To summarize present knowledge regarding the relation between oxidative stress and development of bronchopulmonary dysplasia (BPD).
Methods: Relevant literature searched at Pubmed and other sources.
Results: Oxidative stress is generated in a number of conditions and by a number of causes such as inflammation and hyperoxia. Ontogenic aspects are discussed. Oxidative stress as physiological regulators, its relation to transcription factors and inflammation is summarized. The role of oxygen and antioxidant therapy and newborn resuscitation for development and prevention of BPD as well as new therapeutic modes especially the use of growth factors, gene therapy and stem cells, are briefly discussed.
Conclusion: Oxidative stress and BPD are associated. A better understanding of this association is necessary in order to reduce the severity and the incidence of the condition.
Non-selective multifetal pregnancy reduction is carried out to reduce healthy higher order multiple fetuses to one or two fetuses. No studies exist to show any benefit of this practice and a Cochrane review, as well as investigators in the field, have not found any justification for such practice. From a medical point of view, this non evidence-based practice is not following good clinical practice. Any practice that transfers more than one or two embryos, for instance due to commercial interests, should be abandoned by the international medical community because multifetal pregnancies can, to a large extent, be avoided by transferring only one or a maximum of two fertilized eggs by in vitro fertilization. Further, ovarian stimulating programs should strictly adhere to protocols aiming at mono-ovulation.
The effects on pulmonary artery pressure (PAP) and
plasma Endothelin-1 (ET-1) were studied in piglets during
severe hypoxemia and reoxygenation for 2 h with
selective inhibition of the endothelin receptors. Two
groups were subjected to selective ETA (ETA group) or
ETB (ETB group) receptor inhibition. During hypoxemia
there was an initial increase in PAP to 36.3 and
34.3 mm Hg in the ETA and ETB groups respectively,
with a decrease to the end of hypoxemia. During reoxygenation
PAP reached a maximum at 5 min with a mean
of 29.6 and 38.4 mm Hg in the ETA and ETB groups
respectively, and then PAP gradually declined towards
baseline. During the 2 h reoxygenation period PAP was
higher in the ETB group than in the ETA group
(p = 0.02). Plasma ET-1 increased from 1.50 and
1.17 ng/L at baseline to 2.07 and 3.18 ng/L at the end
of hypoxemia in the ETA and ETB groups respectively.
Conclusion: ETB receptor inhibition leads to increased
pulmonary vasoconstriction during reoxygenation
following hypoxemia compared to ETA receptor inhibition.
Not only the ETB receptor, but also the ETA receptor
plays a role in maintaining plasma ET-1 levels.
Background: Oxygen supplementation is still part of international resuscitation protocols for premature children. Mechanisms for tissue damage by hypoxia/ischemia in the extreme premature involve inflammation.
Aim and method: To study cerebral inflammation after hypoxia/ischemia and oxygen treatment in the premature, we measured NF-κB activity in 5-day-old transgenic reporter mice in response to experimental hypoxia/ischemia. Results were correlated to cerebral histological evaluation and plasma cytokine levels. A treatment strategy with the antioxidant tempol was tested.
Results: One day after hypoxia/ischemia NF-κB activation was increased compared to controls [mean difference: 10.6±4.6% (P=0.03)]. Exposure to 100% oxygen after hypoxia/ischemia further increased NF-κB activation compared to hypoxia/ischemia alone [mean difference: 15.0±5.5% (P=0.01)]. Histological changes in the brain were positively correlated with NF-κB activity (P<0.001), but we found no significant difference in tissue damage between resuscitation with air and resuscitation with pure oxygen. Administration of tempol reduced NF-κB activation [mean difference: 14.6±5.0% (P=0.01)] and the plasma level of cytokines; however, the histological damage score was not affected.
Conclusion: Cerebral inflammatory response after hypoxia/ischemia in a mouse model with immature brain development corresponding to human prematurity prior to 32 weeks’ gestation was influenced by administration of oxygen. Tempol treatment attenuated inflammation but did not reduce the extent of histological cerebral damage.
Objective: To examine fetal brain injury in the Göttingen minipig following intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational length.
Methods: We performed laparotomy after anesthesia in six pregnant sows. We randomized 29 fetuses to one of four groups: pretreatment with saline or endotoxin followed by 30 min of umbilical cord occlusion or no occlusion. After 48 h we performed a re-laparotomy and examined the fetal brains.
Results: After total asphyxia, brain stem injury was present in the group pretreated with saline (P<0.01 vs. controls) and with endotoxin (P<0.005 vs. controls). Microglia activation was more marked in the brain stem (P<0.05) and posterior white matter (P<0.05) in the asphyxia group than in controls. Two of five fetuses in the asphyxia group had white matter injury, while no white matter lesions were found in the asphyxia/inflammation or endotoxin only groups.
Conclusions: In this Göttingen minipig model, a species closer to humans than animals commonly used in experimental studies of perinatal brain injuries, intrauterine asphyxia following pretreatment with saline caused brain stem and white matter injury. This model can be further developed to study the impact of other intrauterine exposures on brain injury.
Brain-derived neurotrophic factor (BDNF) is highly expressed in the developing brain. It has anti-apoptotic abilities, and protects the neonatal brain. In experimental settings in adult animals, pre-treatment with nicotine has shown increased BDNF levels, indicating a possible contribution to nicotine's anti-apoptotic effect. Apoptosis contributes to the development of brain damage in perinatal asphyxia. We examined the effects of nicotine on apoptosis-inducing factor (AIF), caspase-3 and BDNF in the hippocampus of a neonatal piglet model of global hypoxia. Forty-one anesthetized newborn piglets were randomized to one of four groups receiving different infusions after hypoxia (1) nicotine 130 μg/kg/h, 2) 260 μg/kg/h, 3) adrenaline, and 4) saline, all 2.6 mL/kg/h. Four hours after hypoxia they were euthanized. The left hemisphere/hippocampus was examined by histopathology and immunohistochemistry; the right hippocampus was analyzed using real time PCR. There was a significantly higher expression of BDNF mRNA and protein in the animals treated with nicotine 130 μg/kg/h vs. the saline treated group (mRNA P=0.038; protein P=0.009). There were no differences regarding AIF or caspase-3. We conclude that nicotine (130 μg/kg/h), infused over 1 h after global hypoxia in neonatal piglets, increases levels of both BDNF mRNA and protein in the hippocampus. This might imply neuroprotective effects of nicotine in asphyxiated neonates.