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Kidney Hormone Protects Oxygen-Starved Brain Cells

Already approved drug could help stroke victims

WEDNESDAY, Aug. 8, 2001 (HealthDayNews) --A kidney hormone that is already approved for treating anemia may have another use: preventing the death of brain cells deprived of oxygen.

The researchers who made the discovery hope that the hormone, erythropoietin (EPO), could be used to prevent neurons from damage by stroke and other neurodegenerative diseases, including Alzheimer's and Parkinson's.

Although it's been known for years that EPO makes red blood cells, "it kind of came from left field that it would do something in the brain," says Dr. Stuart Lipton, director of the Center for Neuroscience and Aging at the Burnham Institute in La Jolla, Calif. Lipton co-wrote the study appearing in the Aug. 9 issue of Nature.

However, it wasn't known whether EPO was directly responsible for the effect or whether simply having extra red blood cells -- which carry oxygen -- was enough to protect the brain cells.

Lipton says that EPO seems to affect what is believed to be the common final pathway leading to cell death in many neurodegenerative diseases. In this sequence, glutamate -- the brain's main neurotransmitter -- is overproduced. This triggers the release of too much calcium into brain cells, which ultimately kills the cells.

When the researchers treated rat neurons in a petri dish with EPO, the cells were protected from a model of stroke involving large releases of glutamate. Other studies have since shown that EPO can protect neurons in living rats that undergo stroke.

For patients with stroke, this could mean that treatment with EPO could reduce cell damage, says Lipton.

He adds that the body may already use EPO to protect the brain. Neurologists already know that, after a small stroke that deprives the brain of oxygen, the brain suffers relatively little damage from a subsequent large stroke. Lipton suspects that the oxygen deprivation triggers the release of EPO, which then plays a role in protecting the brain from the larger stroke.

The findings, say the researchers, could also have implications for patients with multiple sclerosis, amyotrophic lateral sclerosis (or Lou Gehrig's disease) and spinal cord damage. In this case, early intervention with EPO could help slow neuron damage, he says.

Dr. Christof Dame, a pediatric neonatologist at the University of Florida in Gainesville, says that from a clinical standpoint, EPO could be used to treat stroke as well as babies born with asphyxia.

What is unclear, says Dame, is whether EPO can cross an intact blood-brain barrier in clinically significant amounts. However, he adds, "you can expect that depending upon the degree of injury, you also have damage to the blood-brain barrier." If the effects of a stroke somehow breach this barrier, he says, the hormone could cross the barrier as well.

Dame says that in the case of stroke, "if EPO is given later than two or three hours [after the stroke], it may be too late to get an optimal effect."

EPO now needs to be tested on these neurodegenerative diseases in animal models and in human trials. Since EPO has already been proven safe in other clinical trials, Lipton says it could proceed slightly faster through human tests.

What To Do

Find out about the five most common stroke symptoms from the National Stroke Association, or look at this general stroke information from the National Institute of Neurological Disorders and Stroke.

You can also check out this information on EPO from the Institute for Transfusion Medicine.

SOURCES: Interviews with Stuart A. Lipton, M.D., Ph.D., professor, and director, Center for Neuroscience and Aging, Burnham Institute, La Jolla, Calif.; Christof F.L. Dame, M.D., pediatrician, postdoctoral fellow, Division of Neonatology, Department of Pediatrics, University of Florida, Gainesville; Aug. 9, 2001, Nature
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