A US lab is developing targeted therapies to treat child brain injury by studying cells and biological pathways.
The work focuses on myelination, the process that creates protective insulating layers around nerve fibres, and how it is disrupted in neurological injuries.
Among the team’s priorities is understanding how this disruption affects preterm babies, who often suffer neonatal brain injuries.
Manideep Chavali, assistant professor of paediatrics at Oregon Health & Science University (OHSU) School of Medicine and the OHSU Doernbecher Children’s Hospital Papé Family Pediatric Research Institute, joined OHSU in 2022.
Originally trained as a chemical engineer, Chavali says his academic and professional background has shaped his curiosity about how systems work, and how breakdowns in those systems can have long-lasting effects.
His independent research programme aims to understand the cellular, molecular and metabolic mechanisms of myelination, and how they are disrupted in neurological injuries and neurodegeneration, where nerve cells gradually lose function.
Chavali said: “We want to understand what kind of cellular, molecular and metabolic alterations occur in preterm babies’ brains.
“We hope our work will help uncover how these processes fail in individuals with certain diseases, so we can then identify strategies to protect and repair white matter and optimise long-term brain health.”
The brain’s white matter acts like wiring that connects different areas, supporting functions such as movement, speech and memory.
For this wiring to work properly, there needs to be a close metabolic partnership between a brain cell type called oligodendrocyte, which helps make myelin, and the blood vessels that deliver oxygen, metabolites and nutrients.
When this partnership breaks down, it contributes to brain damage seen in a wide range of conditions, from early childhood injuries and metabolic diseases to neurodegenerative disorders such as multiple sclerosis and ageing-related dementias.
Chavali’s work aims to understand how these key components work together during normal brain development, and how that relationship changes across different diseases and stages of life.
His recent work has focused on how disruptions in these cellular and metabolic partnerships affect preterm babies, who often suffer neonatal brain injuries.
To understand how these pathways are affected, Chavali and his team take a multidisciplinary approach.
Their research draws on advanced genetic tools, imaging and analysis methods, and human brain tissue samples to uncover the biological processes that keep the brain’s wiring healthy.
Chavali said: “The more we study these cells, the more we discover about how dynamic and complex they are.
“When there is a neurological issue, it was historically thought that the neurons themselves are the cells affected. But the more we study these pathologies the more we understand the glial cells and their role in driving the pathology, and that they also play critical roles in maintaining a healthy brain. It’s an exciting shift in how we think about neurological disease.”
Glial cells are support cells in the brain and nervous system that help protect and maintain neurons.
Chavali’s lab has a strong focus on translational neuroscience, which aims to turn scientific findings into practical treatments.
The team hopes its work will help identify targeted therapies that could improve brain function and quality of life for people affected by various brain disorders.
Chavali said: “When we think about how this work will translate, we think about therapeutic targets, and how we can create therapies and treatments that target these specific pathways that we study in the lab.
“Every clinical impact begins with years, decades even, of basic science research. Hopefully, in the next 10 to 15 years, we’ll be able to bring these findings to actual patients.”
Looking ahead, Chavali plans to focus his research on the shared mechanisms underlying brain injury in preterm babies and neurological disorders in adults, in the hope that targeted therapies might be applicable to various patient populations.
Chavali said: “The vast unknowns about the brain are what drive me.
“The more you don’t know, the humbler it makes you.”
Image: OHSU/Christine Torres Hicks
