Novel mechanism for synergistic responses to systemic maternal inflammation and neonatal hyperoxia exposure on lung development and therapies to improve pulmonary function and reduce bronchopulmonary dysplaisa (BPD)

• Applicant: Professor Dr. Markus Velten
• Subject Area: Anaesthesiology
• Term: from 2010 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 167712457

Maternal inflammation is a major cause of preterm birth and contributes to complications that develop in premature infants. Furthermore, preterm infants often require supportive care including mechanical ventilation and exposure to hyperoxia. Unfortunately, these therapies can also add to the lung inflammatory responses and contribute to the pathogenesis of diseases such as bronchopulmonary dysplasia (BPD). BPD is characterized by arrested lung development and pulmonary fibrosis resulting in impaired gas exchange. Importantly, smaller and more fragile infants have survived in the last several years but the long term consequences of their prematurity and clinical interventions are not known. LPS injection to pregnant rodents leads to pulmonary inflammation in the offspring. Further, rodents exposed to hyperoxia demonstrate arrested lung development similar to that observed in human infants with BPD. The mechanisms associated with impaired pulmonary development in combined systemic maternal inflammation and neonatal hyperoxia exposure remains to be elucidated. Preliminary studies in newborn mice indicate that the combined insults result in arrested lung development and diffuse fibrosis in patterns that mimic BPD. Specific Aim 1 will test the hypothesis that the combination of systemic maternal inflammation and neonatal hyperoxia exposure induces a fibrotic profile that impairs pulmonary development and is more severe than either insult. Specific Aim 2 will test the hypothesis that maternal dietary DHA supplementation will decrease pulmonary fibrosis and lessen the pulmonary function deficits observed in mouse pups born to LPS-treated dams and exposed to hyperoxia and does so by decreasing inflammation.The overall objective of these studies is to identify the molecular profiles involved in impaired pulmonary development and function and to identify inflammation related prevention strategies and therapies that would diminish lung injury and long term lung pathology by decreasing inflammatory responses and in so doing lead to the possible development of strategies in infants that protect infants from developing BPD.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Stephen E. Welty