New Findings Could Help Restore Brain Function After a Stroke

Researchers in the Flanagan Lab at UC Irvine identify communication between brain cells and blood vessels, improving our understanding of brain formation and regenerative strategies for repairing the brain after an injury.

Irvine, Calif., June 25, 2025 — Stroke is a major health concern and a leading cause of death and long-term disability. “One reason stroke is so debilitating is the narrow treatment window, which is less than one day,” says Lisa A. Flanagan, PhD, a professor and vice chair for academic affairs in the Department of Neurology in the UC Irvine School of Medicine. “This means that millions of stroke sufferers have to contend with speech or motor impairments that hinder their everyday lives.”

A long-term goal of the Flanagan Lab she leads at UC Irvine is to better understand communication between important cell types in the human brain in hopes of developing treatments that can improve brain function after a stroke.

A recent study conducted by lab members explored interactions between human neural stem cells, which generate the main cell types in the brain during development, and blood vessel endothelial cells, which help bring nutrients and oxygen to the brain.

“Our study pinpoints the importance of communication between brain cells and blood vessels,” says Flanagan, “which can help us better understand brain formation and regenerative strategies that can be applied when the brain is injured.” The findings appear in a paper published in Nature Communications.

Understanding Brain Formation & Function

The researchers found that the blood vessel endothelial cells send a signal to the neural stem cells, inducing them to form an adult neural stem cell phenotype.

“This process is critical to brain formation, and these more mature neural stem cells persist in specialized areas of the adult human brain,” says Flanagan. “We identified how the endothelial cells were talking to the neural stem cells, and if we interrupt that conversation, we block the formation of adult neural stem cells.”

By staining human brain tissue, the team found contact between blood vessels and neural stem cells (identified with new markers they discovered), suggesting the importance of this signaling in the human brain. “This contact between cell types is also important for maintaining the adult neural stem cell pool by reducing their differentiation and controlling their rate of cell division,” says lead author Brenda Gutierrez, MD, PhD.

“Our findings define a new communication axis between neural stem cells and endothelial cells,” says Flanagan. “We also did not know previously what signals lead to the formation of an adult neural stem cell phenotype, and these studies now identify endothelial cells as drivers of that signaling.”

This is important given that the function of adult neural stem cells differs from that of their developmental counterparts. Knowing the source of these adult cells can lead to studies that can better explain their characteristics and functional capability for brain repair.

Determining How to Rebuild After a Stroke

“This research project was strongly motivated by an understanding of the treatment limitations for stroke, which I became aware of as a member of the neurology department at UC Irvine,” says Flanagan. “We have a world-class stroke and neurovascular team and treatment center at UCI, and their presentations on the causes, diagnoses and therapeutic options for stroke were motivating factors for our research.”

The team is now delving further into communication between neural stem cells and endothelial cells, building on their previous findings that human neural stem cells induce vessel formation.

“Now that we know that endothelial cells also signal to neural stem cells, we can design experiments to better understand the communication between these important cell types and hopefully use these signals to help rebuild after stroke,” says Flanagan. Rather than focusing on a single cell type, they hope that considering both neural stem cells and endothelial cells when developing repair strategies will lead to better therapeutic options.