In these neurologic diseases, nerve cell death is thought to be carried out in part by a huge release of glutamate, an important signaling molecule in the brain. In their experiments with brain cells and brain tissue from rats, the Hopkins researchers used glutamate to simulate the aftereffects of a stroke. After strokes and other injuries to the brain, levels of glutamate rise, triggering a number of chemical reactions, including an increase in COX-2 production and prostaglandin production. Increased COX-2 activity then leads to further neuron death.

The new findings come in the wake of two previous studies Andreasson has worked on, each finding unexpected protective roles for another prostaglandin produced by COX-2. In one, a different prostaglandin (PGE2) prevented brain cells from dying after a stroke. In the other, mice lacking a docking point for the PGE2 experienced strokes far more severe than normal animals.

Andreasson is now trying to determine if these prostaglandins have a similar protective effect in mouse models of Lou Gehrig's disease, in which excessive glutamate is believed to damage neurons, and will begin work to see if the beneficial side of PGD2 activity can outweigh its toxic activity.

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Contact: Joanna Downer or Katherine Unger
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
14-Feb-2005