Researcher(s)
- Destiny Heim, Neuroscience, University of Delaware
Faculty Mentor(s)
- Jaclyn Schwarz, Psychological & Brain Sciences, University of Delaware
Abstract
Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal mortality worldwide. HIE is a perinatal brain injury caused by reduced blood flow and oxygen to the brain. One of its primary risk factors is inflammation in the mother, placenta, or amniotic fluid around the time of birth. The only approved treatment, therapeutic hypothermia (TH), is effective only within 6 hours of the hypoxic insult, yet the injury is often not recognized that early. Therefore, new treatments effective over a broader therapeutic window are urgently needed. In collaboration with Dr. Wright-Jin at Nemours Children’s Hospital, we investigated the therapeutic potential of T cells in neonatal HIE. T cells are immune cells that circulate through the bloodstream and migrate to sites of injury or infection. Although the healthy brain contains few T cells, hypoxic injury promotes their recruitment. The brain also contains resident immune cells called microglia, which, like T cells, produce Interleukin-33 (IL-33), a molecule released during tissue damage that regulates inflammation and promotes tissue repair. In this study, cultured BV2 mouse microglial cells were used to determine whether IL-33 could reduce the pro-inflammatory response following inflammation and hypoxia. Cells were exposed to lipopolysaccharide (LPS; 1 ng/ml), followed by hypoxia (1% oxygen vs. ~20% air) in glucose-free media to induce inflammation and metabolic distress. IL-33 (100 ng/ml) was administered 6 hours after hypoxia. Twenty-four hours later, cells and culture medium were collected for analysis of pro- and anti-inflammatory molecules. We found that the microglial response to hypoxia depended on prior LPS exposure and the timing of IL-33 treatment. These findings improve our understanding of inflammation-targeted therapies and may help identify a novel therapeutic approach for HIE.