Analyzing the therapeutic potential of anti-inflammatory drugs in brain development, neuronal activity and long-term outcomes after birth asphyxia

Birth asphyxia or neonatal hypoxia is a medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough to cause harm, usually to the brain. It remains a serious condition which causes significant mortality and morbidity. Neonatal hypoxia is a global insult, which can damage all organs, but the brain is especially vulnerable to hypoxia, making it the special concern for clinicians. Indeed, in a proportion of the infants, brain damage will manifest as either mental, such as developmental delay or intellectual disability, or physical, such as cerebral palsy.

Perinatal asphyxia happens in 2 to 10 per 1000 newborns that are born at term, and a higher proportion in babies born prematurely. The World Health Organization (WHO) estimates that 4 million neonatal deaths occur yearly due to birth asphyxia, representing 38% of deaths of children under 5 years of age. The effect of perinatal asphyxia on the brain and development of babies is poorly understood. We know that babies suffering from hypoxia may develop neurological outcomes and current treatment are not effective in a subset of infants, more importantly current treatments present a short time-window to be effective and need to start within the first 6 hours after birth, e.g. therapeutic hypothermia. This project will study the role of inflammation in hypoxia and how affect brain development and explore ways to improve neurological outcomes. To achieve this, we will use a combination of pre-clinical models and clinical data. We will evaluate novel therapeutic targets and, also, we will evaluate the therapeutical window by testing its efficacy later life. In parallel, we will evaluate if we could identify the sub-set of infants who will respond to anti-inflammatory therapy.

Award Date
01 July 2022
Award Value
€368,783.40
Principal Investigator
Professor Eva Jimenez-Mateos
Host Institution
Trinity College Dublin
Scheme
ILP