Growth Factor Protects Brain from Stroke Damage
Finding could lead to the development of new stroke treatments

A naturally occurring growth factor called neuregulin-1 protects brain cells from damage resulting from stroke, according to an animal study conducted by CBN researchers at Morehouse School of Medicine (MSM). The finding, reported in the current online edition of the Journal of Cerebral Blood Flow and Metabolism, could lead to the development of new stroke treatments.

Stroke, the third leading cause of death in adults in the United States, occurs when blood flow to the brain is interrupted. Deprived of oxygen, brain cells die within minutes, causing inflammation and further damage to tissue surrounding the site where blood flow is obstructed.

In the study, a research team led by CBN molecular core head Byron Ford, PhD, of the MSM Neuroscience Institute and Department of Anatomy and Neurobiology, examined the effects of administering neuregulin-1, a protective compound which neurons produce naturally, to rats after surgically induced strokes. The scientists discovered neuregulin-1 reduced cell death by 90 percent compared to rats that did not receive it. The compound also protected neurons from damage even when administered as long as 13 hours after the stroke’s onset.

In DNA microarray analysis of the affected brain tissue, Ford and his team determined neuregulin-1 produces its protective effects by turning on or off nearly 1,000 genes that regulate cell death and inflammation. Neuregulin-1 also blocks the production of free radicals, compounds that have been implicated in cell injury and aging.
Currently, a drug called TPA is the only available stroke treatment, and must be administered within three hours of stroke onset to be effective.

“The biggest potential benefit of neuregulin-1 is that its therapeutic window is much longer than TPA, potentially up to 48 hours,” said Ford. “It also appears to easily cross the blood-brain barrier and does not produce any obvious side effects in rats.”

Ford has filed two provisional patents for the uses of neuregulin-1 as a stroke treatment and promoting the growth of endogenous neural stem cells to replace damaged neurons. He also was recently awarded a five-year R01 grant from the National Institute of Neurological Disorders to begin pre-clinical studies of neuregulin-1 as a stroke therapy. As part of this project, Ford will test neuregulin-1 in additional animal models and conduct imaging studies to determine the optimal therapeutic window for the compound to be protective. He also intends to better characterize the molecular processes involved in the stroke process to facilitate the development of novel stroke therapies.

In collaboration with CBN colleague Kerry Ressler, MD/PhD, an Emory University researcher, Ford also is studying the function of neuregulin-1 in the brain’s fear mechanisms and its possible connection with schizophrenia. Schizophrenia, which is characterized by a dysfunction of the brain’s fear mechanisms, has been linked to a mutation in the neuregulin-1 gene. Other studies have found that schizophrenics have lower than normal brain levels of neuregulin-1.

Co-authors of Ford’s latest stroke study include graduate student DaJoie Croslan, postdoctoral fellow Adalynn Harris, PhD, and research assistant Gregory Ford, all of the MSM Department of Anatomy and Neurobiology, and Zhenfeng Xu, MD/PhD, a postdoctoral fellow at Johns Hopkins University.