|
| Barriers to Accessing the Brain | |
(i) Do pathogens, inflammatory mediators and inflammatory cells access the fetal and neonatal brain using the same
mechanisms as in animal and adult models? | |
|
| Infection | |
(i) Which leukocyte populations and which specific proinflammatory cytokines are the primary triggers for brain damage of
premature infants? | |
(ii) What is the origin and the role of proteins differentially expressed in amniotic fluid associated with chronic
chorioamnionitis cases compared to acute chorioamnionitis in the amniotic fluid detected by proteomic analysis? | |
| (iii) What is the role of microglial IL-1β signaling and TIMP expression in perinatal brain inflammation and repair? | |
| (iv) What are the mechanisms of brain injury from LPS-activated microglia leading to PVL? | |
|
| Cerebral Palsy | |
| (i) What are the roles of inflammatory cytokines in preterm infants that develop CP? | |
(ii) To what extent does an altered inflammatory response and persistent neuroinflammation originating in the perinatal period
play a long-term role in preterm children with PVL-induced CP? | |
|
| Dual Role of Cytokines | |
(i) What variables determine neuroprotective and neuroinflammatory properties of cytokines (e.g., timing, type, location, and
duration of injury)? | |
|
| Cytokines and Genetic Susceptibility to Perinatal Brain Injury | |
| (i) Which cytokine gene polymorphisms predispose to CP? | |
| (ii) How do cytokine gene polymorphisms interact with perinatal infections to cause CP? | |
|
| Cytokine Biomarkers of Perinatal Brain Injury | |
(i) Are there accurate diagnostic, predictive, and prognostic cord blood and neonatal plasma cytokines biomarkers that reflect
CSF cytokine levels or inflammatory events within the brain? | |
(ii) Are there biomarkers specific for precise inflammatory conditions associated with white matter injury (e.g., differentiating
between septicemia and necrotizing enterocolitis) that will provide time-sensitive, pathogen and treatment specific information? | |
|
| Prevention and Treatment of Perinatal Brain Injury | |
(i) Which anti-inflammatory cytokines and treatments will safely and effectively alter cytokine profiles promoting
neuroprotection and repair? | |
| (ii) What is the optimal timing of such treatments? | |
|
