X-Message-Number: 12420 Date: Tue, 14 Sep 1999 16:28:00 -0400 From: Jan Coetzee <> Subject: NOS and ROS Dual action drug protects brain against stroke, trauma NEW YORK, Sep 13 (Reuters Health) -- A new drug with two different injury protection properties reduces brain cell damage in animal models of stroke and head trauma. Two key processes contribute to the damage seen after ischemia -- an interruption of blood flow to the brain. An enzyme called nitric oxide synthase (NOS) causes overproduction of a damaging chemical, nitric oxide (NO). At the same time, strong oxygen compounds called reactive oxygen species (ROS) cause widespread cell damage. ``Our results suggested that controlling both ROS and NO is more efficient (in preventing brain damage) than the inhibition of only one of these,'' according to Pierre-Etienne Chabrier from Beaufour-Ipsen Research Laboratories in Cedex, France, and colleagues. Their results are published in the September issue of the Proceedings of the National Academy of Sciences. The researchers tested BN 80933 in rats and gerbils with stroke-like conditions and in mice subjected to head trauma. BN 80933 contains an antioxidant (a chemical that prevents ROS effects) linked to an NOS blocker. The drug proved effective in preventing cell death, the report indicates. BN 80933 reduced the death of brain cells by 60% to 70% in rats, and the rats that received BN 80933 had better functioning after their ischemic episodes, the scientists explain. In gerbils subjected to ischemia of the entire brain, BN 80933 more than doubled the number of surviving brain cells, the investigators report. Mice that sustained head trauma were also protected by BN 80933, according to the results. When administered 5 minutes after injury, BN 80933 reduced the damage to the mice by 48% to 58%, depending upon the dose given. ``All these results indicate that BN 80933 represents a class of potentially useful therapeutic agents for the treatment of stroke or trauma and possibly neurodegenerative disorders that involve both NO and ROS,'' Chabrier and colleagues conclude. ``Most important is that the protection conferred by this agent is sustained; thus, it can be given 4 to 8 hours after injury and still provide significant neuroprotection,'' writes Valina Dawson of Johns Hopkins University School of Medicine in Baltimore, Maryland, in a related commentary. ``This approach, which one could envisage being employed with alternative targets, is particularly innovative.'' SOURCE: Proceedings of the National Academy of Sciences USA 1999;96:10824-10829, 10557-10558. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=12420