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Old antibiotic may find new life as a stroke treatment
Date:5/19/2008

s. Every study patient will get one of four doses, starting with 200 milligrams, the most common dose already used, and increasing incrementally up to 700 milligrams. Theyll get half their first dose at subsequent 12-hour intervals for a three-day period then be followed for 90 days.

We are going to be drawing samples from patients to make sure we achieve the concentrations that we want in the blood, plus we want to define the half-life in stroke patients to see if its different than in the younger patients who take it for other reasons, says Dr. Fagan. Newer intravenous antibiotics have replaced minocycline in the United States, but an oral version is used to treat conditions such as acne and rheumatoid arthritis. If the half-life is longer, we can give it less frequently. We are really fine-tuning the dose, she says. Theyll do this by looking in the blood for biomarkers, indicators of inflammation, to see if inflammatory factors go up after three days. It may give us a clue we should treat patients longer, says Dr. Fagan, a co-investigator on the studies leading to minocyclines use in rheumatoid arthritis.

One way minocycline fights inflammation is by inhibiting microglial cells, white blood cells activated by a stroke, says Dr. Hess. When they get activated, they get angry and produce materials that damage the brain. The inflammatory cascade is bad and good. Early on its bad, later on it may actually do some good things, he says. Typically these microglial cells are sentinel immune cells for the brain, helping eliminate infections and secreting factors that support neurons. However, acutely in a stroke, brain tissue can become their target. They are basically cleaning house at first, then later, they are supportive, releasing growth factors and promoting the growth of new blood vessels, adds Dr. Fagan.

Minocycline also blocks matrix metallo-proteinases, also released during stroke, which destroy the basement membrane of blood vessels.
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Contact: Toni Baker
tbaker@mcg.edu
706-721-8596
Medical College of Georgia
Source:Eurekalert  

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