A daily dose of an old antibiotic may help people with diabetes avoid a stroke, or at least minimize its damage, according to a new study by researchers at the Medical College of Georgia that was recently reported in the Journal of Cerebral Blood Flow and Metabolism. The drug, minocycline, which is known to be an angiogenesis inhibitor, appears to reduce the formation of leaky, twisted blood vessels in the brain that increases stroke risk in diabetics.
The researchers, led by Dr. Adviye Ergul, physiologist in the MCG Schools of Medicine and Graduate Studies, focused on the blood vessels of diabetic rats. They found that even moderately elevated blood glucose levels result in thicker, twisted blood vessels that tended to leak. People with diabetes are at increased risk for a dangerous combination of clot-based and bleeding (hemorrhagic) strokes because a clot is followed by the growth of leaking blood vessels—a process called hemorrhagic transformation.
Much of the harmful blood vessel growth in people with diabetes is triggered when elevated glucose activates proteins called matrix metalloproteinases or MMPs. MMPs are a key part of the process of new blood vessel growth (angiogenesis). Leaky, contorted blood vessels like those found in diabetic stroke victims are also characteristic of abnormal angiogenesis associated with diabetic retinopathy and cancer.
“Minocycline is one of a number of drugs that blocks angiogenesis by inhibiting MMPs,” said Dr. William W. Li, President of the Angiogenesis Foundation. “MMP inhibitors are being studied in clinical trials to treat diabetic retinopathy and cancer based on the same mechanism of action as found in this study.”
Another MCG research team, led by Dr. David Hess, stroke specialist and chairman of the Department of Neurology, showed that minocycline given alone or with tPA, a clot dissolver and the only FDA-approved stroke treatment, can also work after a stroke to help minimize damage from reperfusion injury, the sudden influx of oxygen and blood to the stroke site. Giving the drugs together has a beneficial synergy, since tPA increases bleeding risk while minocycline decreases the risk.
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