Goals and Objectives:
Neurodevelopmental disorders such as cerebral palsy (CP) and autism are common chronic childhood disorders with no effective cure. Half a million children under the age of 18 in the US have CP, and an estimated 1 in 6 children have some form of developmental disability. Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of CP and related disabilities. This project is focused on reducing brain damage and its associated morbidity and mortality risks in infants exposed to perinatal hypoxia-ischemia (HI), employing a mouse model to examine post-injury impacts of intervention.
Therapeutic hypothermia is an intervention known to reduce brain injury in term infants after perinatal asphyxia, but protection is typically incomplete and rates of mortality and severe disability remain high. Therapeutic hypothermia can also cause immune dysregulation and increase pro-inflammatory responses that are associated with worse outcomes. Moreover, rewarming may trigger seizures or increase glutathione consumption, leading to altered redox balance. Therefore, a critical need exists for complementary therapies that improve neuroprotection and address the negative effects of hypothermia and rewarming. This preclinical research project addresses this need by examining the effects of combining hypothermia with nanotherapeutic approaches for targeted delivery of drugs to injured neurons, activated microglia and reactive astrocytes in an established mouse model of HIE. This work will lead to new strategies for targeted delivery of adjunct therapies for use with hypothermia, enabling sustained neuroprotection to reduce the incidence of neurodevelopmental disabilities, including CP, in neonates exposed to perinatal asphyxia.