Researcher(s)
- Lindsay Gallagher, Neuroscience, Nemours Children's Hospital
Faculty Mentor(s)
- Elizabeth Wright-Jin, Neurology, Nemours Children's Hospital
Abstract
Neonatal Hypoxic Ischemic Encephalopathy (HIE) is a common injury caused by impaired blood and oxygen circulation to the brain, leading to an inflammatory response. HIE can have many serious downstream effects, such as cerebral palsy, autism, and seizures. Alginate hydrogels can be used as a drug delivery technique to slowly release immune molecules over time. This can provide support to the injury over a period of one week. Interleukin-33 (IL-33), which is a cytokine that recruits regulatory T-cells (Tregs), was added to alginate hydrogels. Tregs suppress microglia activity and further downstream inflammation responses in the brain. These hydrogels have been tested using the Rice-Vannucci (RV) injury model in C57BL/6 mice. Both functional and histological outcomes were assessed. This was done through gait analysis, grip strength, and hematoxylin and eosin (H&E) staining of brain sections. Male mice treated with RV and a blank hydrogel displayed the lowest normalized grip strength and the most abnormal gait. They also demonstrated the largest ventricular area (indicating the largest brain injury). Alginate hydrogels loaded with IL-33 displayed improved motor functions and a smaller ventricular area. In addition, females displayed a less severe injury when compared to male mice. Overall, IL-33-loaded alginate hydrogels are a promising technique for the treatment of HIE, improving both functional and histological outcomes.