Protecting the Preterm Brain: Dr. Crouch’s Quest to Treat Brain Bleeds
For physician-scientist Elizabeth "Betsy" Crouch, MD, PhD, the drive behind her research stems from conversations she has had too many times.
She has often sat with parents whose premature babies suffered a devastating brain bleed known as germinal matrix hemorrhage (GMH). This condition affects about 20% of infants born extremely prematurely (24-28 weeks), occurring in a brain region where blood vessels are uniquely fragile and potentially leading to cerebral palsy or death.
When families ask Crouch about treatments or clinical trials to help their baby, the answer is always the same: there are none. Within the UCSF Department of Pediatrics, Crouch’s NIH-supported research aims to change that answer.
Leading Bench-to-Bedside Science
Crouch’s work highlights what makes UCSF a leader in caring for the smallest, sickest newborns: scientists and clinicians tackling pressing health issues side by side. As both a neonatologist and a neuroscientist, Crouch embodies UCSF’s signature bench-to-bedside approach that connects work in the clinic with work in the lab.
“Seeing this condition firsthand gives me hope that every experiment is a small step toward changing that answer for future families,” says Crouch, an assistant professor of Pediatrics in the UCSF Division of Neonatology.
Her lab is now creating the first developmental roadmap of the affected, fragile brain vessels. “For a long time, GMH has been attributed to ‘vascular cell immaturity,’ but no one knew what that meant on a cellular or molecular level,” Crouch explains.
Using advanced sequencing, her team identified a novel "vascular stem cell," a progenitor that creates different types of blood vessel cells. “Now we can begin to pinpoint the exact cell type vulnerable in GMH,” she says. This foundational discovery gives the field its clearest therapeutic target to date.
Why Do These Vessels Bleed?
What makes these immature cells and vessels so prone to bleeding? “That’s the key question,” Crouch acknowledges. “We don’t know yet, but there are clues.”
Previous studies suggest less structural support or fewer protective cells. Mouse studies hint at vulnerability to low oxygen. Crouch’s discovery of a vascular stem cell and her work on building the first developmental roadmap of fragile brain vessels give the field its clearest therapeutic targets to date.
“Immaturity, in this context, is both structural and functional. It’s about timing, coordination, and resilience that hasn’t yet been built,” she explains. “Now, armed with a comprehensive understanding of vascular development, we can systematically test different interventions.”
From Mini-Brains to Future Cures
To test potential interventions, UCSF is among a select group of institutions using innovative human cerebral organoids: "mini-brains" grown in the lab. These models accelerate the path toward treatment by enabling researchers to watch how human vascular stem cells form, mature, and respond to injury in a controlled system, mirroring human biology more closely than animal models alone.
“They also allow us to test potential therapies, such as growth factors, small molecules, and even gene targets, in a human context before moving to preclinical models,” Crouch explains. “Organoids are a bridge between discovery and translation, helping us move closer to interventions that could one day protect premature infants.”
A Future Where Hope Replaces Fear
“A future with a treatment for GMH would mean a diagnosis no longer feels like inevitability. We could intervene and preserve normal brain development,” Crouch envisions.
Clinically, that means fewer severe hemorrhages and better long-term outcomes. “For families, it would provide a new source of hope, and for those of us who care for these infants, it would mean finally having something meaningful to offer,” says Crouch.
Backed by strong NIH funding and embedded in a highly collaborative ecosystem — from genomics and stem cell biology to world-class neonatal intensive care — Crouch and UCSF are uniquely positioned to translate groundbreaking basic science into the first-ever therapy for germinal matrix hemorrhage.
Driven by the families who inspire it, the research led by Crouch and her colleagues in the UCSF Division of Neonatology continues to transform the future of health for all newborns.