However, clinical trials of drugs to keep these receptors closed to calcium have largely failed, in large part because they disrupt normal function of the channels in otherwise unaffected brain areas.
Now, however, researchers have discovered the distinct molecular malfunction that renders some neurons particularly vulnerable to stroke damage. Those vulnerable are neurons are in the hippocampus, the brain region central to learning and memory. The researchers' findings, they say, could lead to drugs targeted to correct this specific malfunction, without compromising other brain cells.
The researchers, led by Dr. YouMing Lu of the University of Central Florida and the University of Calgary, published their findings in an article in the March 2, 2006, issue of Neuron.
Their studies concentrated on one of the glutamate receptors, called the AMPA receptor, that opens to cause calcium "poisoning" of neurons after ischemia. The other major receptor involved is called the NMDA receptor.
The researchers found in their experiments with rats that the AMPA receptor allows calcium influx in ischemia because such ischemia causes the receptor to be abnormally constructed in the first place. They found that in vulnerable neurons, early in the construction of the receptor, the machinery for correctly "editing" one part of the genetic blueprint, called messenger RNA, for a key AMPA receptor subunit has been disrupted. The editing consists of a pinpoint alteration in the messenger RNA when
Contact: Heidi Hardman