Research sheds light on neonatal brain hemorrhage
Neonatal intraventricular hemorrhage causes inflammation and white matter injury after preterm birth. IVH causes progressive brain injury after time, and faculty in the Department of Pediatric Surgery and the Department of Diagnostic and Interventional Imaging conducted a study to determine why this may occur.
“Innate immune activation and white matter injury in a rat model of neonatal intraventricular hemorrhage are dependent on developmental stage” was published in June 2023 in Experimental Neurology. Understanding how intraventricular blood affects outcome may provide important insights into IVH pathophysiology and innate immune development.
“This work, which used small animal MRI, flow cytometry, immunohistochemistry, and human data from our cerebrospinal fluid biobank, demonstrated that as the neonatal brain matures, there is a stronger immune response to blood products,” explained Brandon Miller, MD, PhD, associate professor of pediatric surgery and lead author. “This may be why hydrocephalus often takes time to develop after neonatal IVH.”
IVH occurs during the early postnatal period, during which both the central nervous system and immune system are developing. IVH activates innate immune cells, injures developing white matter, and induces hydrocephalus. Hydrocephalus occurs in two out of every 1,000 births, when cerebrospinal fluid builds up within the ventricles of the brain.
The study was designed to examine inflammation and white matter injury across a narrow and developmentally important age range in response to IVH. The researchers found that white matter pathology from IVH is due in part to innate immune activation and that the developmental stage of the innate immune system is a key determinant of IVH pathology.
“We sought to determine if timing of IVH affected the acute inflammatory response and long-term outcome,” Miller said. “We hypothesized that IVH occurring at an earlier developmental stage would induce worse white matter pathology; however, this was not the case. We found that the immune response of older animals was more robust, and that IVH later in development resulted in more severe injury.”
These data are the first to show that the outcome of IVH is critically dependent on the developmental stage of the brain and suggest that white matter injury after IVH is dependent on a strong innate immune response that is not present early in development.
Future work studying CSF flow will better determine to what extent ventricular changes are due to white matter loss versus obstruction of CSF outflow. Future studies on modulating innate immune activation could improve IVH outcomes.
Additional McGovern Medical School authors included Miriam Zamorano, Scott Olson, Candice Haase, David Sequeira, and Charles Cox, from the Department of Pediatric Surgery, and Juan Herrera, Shuning Huang, from the Department of Diagnostic and Interventional Imaging.