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Experimental treatment halts hypoxic-ischemic brain injury in newborns
Date:7/29/2009

neonatal cerebral hypoxic-ischemia, according to the researchers. The enzyme in this case, tPA, normally breaks down proteins and other molecules to eliminate blood clots.

The current study, posted on the journal's website this month, included one-week-old rats in which brain hypoxia-ischemia was induced. The researchers found that hypoxia-ischemia leads to increased tPA activity. The enzyme then damages the brain blood vessels and the blood-brain barrier. The blood-brain barrier is a protective system designed to prevent invasions of blood-borne materials, in particular inflammatory cells or potential contaminants, into the central nervous system.

Dr. Kuan and his colleagues report that elevated tPA activity is triggered earlier in brain hypoxia than other proteases, particularly matrix metalloproteinases, in the progressive molecular process that leads to brain injury. This makes it a better target for therapeutic intervention to shut down the injury process early.

To test the importance of plasminogen activator in HIE, the research team examined the therapeutic effect of injecting PAI-1 into newborn rats suffering from the brain blood flow reduction and systemic hypoxia. The enzyme inhibitor was injected into the intracerebroventricular region of the brain, which includes a system of canals that distribute cerebrospinal fluid throughout the organ.

The researchers found that injection of PAI-1 greatly reduced the activity of both tPA and another brain enzyme, urokinase-type plasminogen activator. It also blocked hypoxic-ischemia-induced activation of matrix metalloproteinases and damage to the blood-brain barrier. The researchers also applied magnetic resonance imaging tests and microscopic analysis of brain tissues, which showed that PAI-1 treatment greatly reduced brain edema, axonal degeneration and the loss of brain tissue.

Dr. Kuan said additional studies are needed to test the effectiveness and safety of PAI-1 t
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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