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