Retigabine preserves brain tissue in mouse models of stroke
Retigabine, a drug approved to treat epilepsy, protected the brain against the effects of ischemic stroke in a study conducted at The University of Texas Health Science Center at San Antonio. Findings are in The Journal of Neuroscience.
New research from The University of Texas Health Science Center at San Antonio suggests that an already-approved drug could reduce the debilitating impact of strokes. MIce that had treatment with a drug called retigabine after a stroke were able to traverse a balance beam without difficulty. Untreated mice displayed a pronounced loss of coordination.
Drs. Mark S. Shapiro, Sonya Bierbower and James D. Lechleiter/The University of Texas Health Science Center at San Antonio
Sonya Bierbower, Ph.D., and Mark S. Shapiro, Ph.D., of the School of Medicine at the UT Health Science Center, compared treated and untreated mice after a stroke. In a balance beam exercise, untreated mice exhibited a pronounced loss of coordination with slips and falls. Retigabine-treated mice had no difficulty with balance, ambulation or turning around on the beam. See the video.
"You couldn't even tell they had a stroke," Dr. Shapiro, professor of physiology and senior author, said. "They ran across the balance beam like gymnasts."
Effects in tissue
Brain tissue of the treated mice showed significantly reduced damage, compared to untreated mice. Protective effects of the medication were observed up to five days after the stroke, said Dr. Bierbower, lead author and postdoctoral fellow in the Shapiro laboratory.
In an ischemic stroke, blood flow to the brain is suddenly cut off because a vessel gets blocked. The lone treatment approved by the U.S. Food and Drug Administration (FDA) is a clot-busting drug called tPA (tissue plasminogen activator). Since tPA severely thins blood, it can't be administered to many stroke patients.
The initial injury, the stroke, is followed by a cascade of nerve cell death in the brain. Retigabine works on a different system than tPA, acting directly on the nerve cells to minimize damage.
Retigabine and similar agents open specific proteins called potassium ion channels, whose action stops the electrical activity of nerve cells in the brain. "We thought if we could stop the neurons from firing, thus stopping their electrical activity, we could conserve their resources until their blood supply was restored," Dr. Shapiro said. "This proved to be the case."
Because retigabine is FDA approved under the American brand name Ezogabine as an anticonvulsant, physicians may use it off label in stroke patients. FDA approval for specifically this drug as stroke therapy will require a clinical trial to be conducted, and a team of neurologists and neurosurgeons at the Health Science Center is considering it, Dr. Shapiro said.
"As a leading cause of death and disability, stroke poses a major risk to our society," said David F. Jimenez, M.D., FACS, professor and chairman of the Department of Neurosurgery at the Health Science Center. "It is very exciting to see that our collaborative work with our colleagues in physiology could provide a superb way to ameliorate the harmful effects of stroke on our patients."
Drs. Bierbower and Shapiro both received funding from the National Institute of Neurological Disorders and Stroke to conduct this study. A grant from the American Heart Association has been applied for to further this work. James D. Lechleiter, Ph.D., professor of cellular and structural biology in the School of Medicine, is a co-author of the study.
The University of Texas Health Science Center at San Antonio, one of the country's leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university's schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 31,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways "We make lives better®," visit http://www.
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