Doctors currently use a modified version of activated protein C or APC to reduce inflammation or increase blood flow in patients with severe sepsis, and last year neuroscientist Berislav Zlokovic, M.D., Ph.D., led a team that showed that the compound also protects the cells that are vital to supply blood to the brain. In the latest paper, Zlokovic and colleagues show that the compound also directly protects vital brain cells known as neurons.

While several compounds have been shown in the laboratory to protect neurons, the latest finding is of special interest for a few reasons, says Zlokovic, who heads the Frank P. Smith Laboratories for Neurosurgical Research.

"This is a compound that's naturally present in your body, and it's already being used to treat people it's not a chemical tucked away in a laboratory," he says. In addition, one of the biggest side effects of APC is increased bleeding, and the team showed that the protection APC bestows is separate from its ability to increase blood flow and reduce inflammation. The findings open the possibility of creating a new compound that would keep brain cells healthy but without causing major side effects like increased bleeding.

Working closely with Zlokovic, Huang Guo, research assistant professor of Neurosurgery, and Dong Liu, post-doctoral fellow, showed that APC protects neurons by activating receptors known as PAR-1 and PAR-3. They showed that the compound helps protect against a variety of causes of "apoptosis," or programmed cell death, one of the major ways we all lose brain cells.

Preventing neurons from killing themselves committing apoptosis when they shouldn't is a broad goal of researchers. Apoptosis often happens when c
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Contact: Tom Rickey
trickey@admin.rochester.edu
585-275-7954
University of Rochester Medical Center
18-Feb-2004