Cerebrospinal Fluid Profiling in Preterm Infants with Hydrocephalus: Defining a Novel Pathway to Disability
Abstract
Military women face unique physical, social, and environmental challenges and are at risk for spontaneous preterm delivery, particularly within 6 months of deployment. Their preterm infants are at risk for developing hydrocephalus or water on the brain. This disease is a debilitating neurological condition, characterized by the buildup of excess cerebrospinal fluid (CSF) in the brain and enlarged chambers within the brain that house CSF (brain ventricles). In North America, hydrocephalus produced by the presence of blood in the brain ventricles represents the most common cause of pediatric hydrocephalus (post-hemorrhagic hydrocephalus – PHH). Additionally, it is associated with the worst neurological consequences in newborn medicine and enduring, complex neurosurgical care. Inflammation has been suggested to play a role in the severity of hydrocephalus, which can cause damage to different parts of the brain, especially the areas surrounding the brain ventricles. Notably, the damaged cells or parts of them (i.e., small capsules from the cells called exosomes) can fall into the CSF. From there, these exosomes can travel throughout the brain and cause more inflammation. To date, no one has identified the complete profile of cells and cellular components present in the CSF in PHH. Because these profiles could reveal promising drug targets that would improve the treatment of hydrocephalus, the proposed studies are new and urgently needed. Therefore, our goals are to: (1) define the cell composition of the CSF from infants with PHH; (2) examine the roles that exosomes from the CSF play in producing brain inflammation in hydrocephalus and altering important mechanisms that affect brain development; and (3) analyze the role of one specific inflammatory protein (S100A9) in PHH as a potential therapeutic target. This project is innovative in that (1) no studies have analyzed the cellular composition of the CSF in human infants with PHH, and (2) our analysis of a specific target for a drug (S100A9) could help to improve the treatment of these most fragile infants. The successful completion of our studies will increase knowledge of the damage hydrocephalus causes in the brain and set the stage for future clinical trials on drug interventions for the treatment of hydrocephalus. Ultimately, drug treatments could be incorporated into the immediate management of hydrocephalus in the clinic, and improved treatments would benefit all patients who suffer the long-term consequences of hydrocephalus.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310075
Entities
People
- Maria Garcia Bonilla
Organizations
- United States Army
- Washington University in St. Louis