Researcher(s)
- Lucy Maxim, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Jaclyn Schwarz, Psychological & Brain Sciences, University of Delaware
- Brian Kwee, Biomedical Engineering, University of Delaware
Abstract
Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of neonatal fatalities worldwide. The only current treatment, therapeutic hypothermia (TH), has many limitations. First, it must be performed within 6 hours of birth, and even then, it’s not effective at preventing disabilities and all fatalities. Even with TH, 30% of severe cases still end in fatalities, with male neonates having an increased risk of severe HIE compared to their female counterparts. Another risk factor for HIE is maternal immune activation (MIA), with nearly 40% of HIE events being associated with MIA. Due to the ineffectiveness of TH in treating severe HIE and its limited availability, numerous attempts have been made to identify alternative treatments using various animal models and molecules targeting immune activation. Among such attempts, IL-33 has been proposed as an alternative to TH. To better understand the potential impacts of IL-33 on the neonatal brain, BV2 cell culture experiments were performed.
Our experimental model used two main groups: normoxia and hypoxia. Of those two groups, half were exposed to lipopolysaccharide (LPS) to stimulate the immune system, thereby simulating MIA. Subsequently, the hypoxia group went through a 6-hour-long hypoxic event approximately 24 hours after LPS exposure. IL-33 was administered at varying time points for both groups, with some not receiving the drug, some receiving it at the start of the hypoxic event, some receiving it 4 hours into the event, some receiving it 6 hours into the event, and some receiving it 4 hours after the end of the event. These time points aim to explore the anti-inflammatory effects of IL-33 for the potential treatment of HIE with associated immune activation and to determine the optimal treatment window.