Research with a mouse model has identified a toxic chemical that is the apparent trigger of cell death secondary to ischemia-reperfusion injury, according to an article in the November 28 issue of the Proceedings of the National Academy of Sciences.

Senior author Ted Dawson, MD, PhD, of Johns Hopkins University, Baltimore, MD, said “We’ve found evidence of it (Poly(ADP ribose)-polymer, or PAR-polymer) in cells following all types of injury.” The research team named the cell death process caused by PAR-polymer “parthanatos,” after Thanatos, the personification of death from Greek mythology.

To establish that PAR-polymer is indeed key in reperfusion injuries linked to myocardial infarctions, ischemic strokes, and a variety of vascular injuries, researchers evaluated normal mice and mice without a functional gene for the enzyme that degrades the polymer. Brains of mice without the key degradative enzyme contained twice as much PAR-polymer as those of normal mice.

The same mice showed a 62-percent increase in the area of cerebral infarction following induction of injury compared with normal littermates. Mice with more than the average amount of the degradative enzyme had less brain damage than normal littermates.

The fate of the cell is irreversible once PAR-polymer sets off the trigger, said Valina Dawson, PhD, another coauthor. “If we could figure out how to block PAR-polymer, we could design drugs that protect the switch and prevent cells from dying after heart attacks, stroke or other injuries,” she said.

Ongoing work is designed to better understand the signaling pathway and how to interfere with the lethal signal cascade.