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Stroke Study Reveals a Key Target For Improving Treatment
Date:6/22/2008

on the same target, but that to cause the blood-brain barrier to leak, they both had to be injected directly into the brain side of the barrier. So, something else must be causing tPA to produce this effect when it is delivered through the bloodstream, which is how it is given during stroke treatment.

That's where the PDGF-alpha receptor comes in. The team looked at the activation of these receptors in the side of the brain where a stroke occurred, compared with the other side, in both normal mice and mice that were deficient in natural tPA. This experiment confirmed that the receptor is crucial to the blood-brain barrier permeability that is caused by tPA activation of PDGF-CC.

Knowing that imatinib is a drug that inhibits the PDGF-alpha receptor, the researchers then tested the drug's effect as a preventive agent.

First, they induced strokes in the mice, then gave some of the mice a dose of imatinib one hour after the stroke began. The mice that received the drug had 33 percent less leakage than those that didn't, and 72 hours later, the mice that received imatinib had 34 percent less damage to the brain than the others.

Finally, the researchers tested the effect of imatinib as a pre-treatment to be given before tPA, to protect against bleeding in the brain. They gave imatinib to mice one hour after the stroke began, and then waited until five hours had elapsed after the start of the stroke before giving tPA.

The level of bleeding in the brain was measured by assessing the amount of hemoglobin in the stroke-affected side of the brain. Mice that had received imatinib before tPA had 50 percent less hemoglobin than those that had not received pretreatment.

This last experiment is especially encouraging for its potential to be translated into clinical practice, says Lawrence. Stroke diagnosis often takes hours, especially if a patient delays getting to the hospital or needs to be transferred to a hospital that offers diagnost
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SOURCE University of Michigan Health System
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