A new class of experimental agents could offer a new avenue for protecting nerve cells following a stroke, Hopkins neuroscientists reported as this issue of Johns Hopkins Magazine was going to press. The agents, called PARP inhibitors, could potentially lengthen the "window of opportunity" for limiting the ravages of stroke, says associate professor of neurology Valina Dawson.

PARP inhibitors appear to protect cells from the chemical assault that occurs when a clot blocks the blood supply. In theory, PARP inhibitors could keep neurons alive while tPA busts through the clot, says Dawson, who collaborated with investigators led by Solomon Snyder, Distinguished Service Professor and director of the Department of Neuroscience.

PARP inhibitors block an enzyme called poly (ADP-ribose) polymerase. Activation of PARP appears to be the culminating link in a molecular chain of events that follow stroke, the neuroscientists report in the October Nature Medicine. When PARP is activated, it starts consuming neurons' energy supply. If the process continues, the enzyme depletes the cells' energy stores, and neurons die. PARP inhibitors might halt this process before the energy supply is depleted, and thus spare cells while blood flow is being restored, says Dawson.

The researchers discovered the role of PARP by creating "knock-out" mice that lack the PARP gene. They induced strokes in these mice and in normal mice brains. After two hours, they untied the artery. Remarkably, the PARP knock-out mice suffered 80 percent less neuronal damage than did the mice whose PARP genes were left intact. "It really is amazing," says Dawson. No other gene has shown as large an impact on cell death following stroke. --Melissa Hendricks

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