Two novel treatments -- a basic compound found in every cell in the body and an extract of green tea -- may prevent brain damage caused from stroke, according to two studies in rats led by a researcher at the San Francisco VA Medical Center.
Both treatments were administered through the nose, rather than intravenously, the conventional method for delivering drugs to the brain.
In one study, rats' brains were subjected to ischemia -- severely reduced blood flow for two hours in a model of stroke. Researchers then administered nicotinamide adenine dinucleotide, or NAD+, immediately after "reperfusion," or resumption of blood flow. Reperfusion is the time when stroke damage actually occurs because brain cells are suddenly exposed to highly reactive and unstable oxygen molecules, which are toxic.
The researchers found that NAD+ reduced brain cell death from reperfusion by 70 to 86 percent compared with rats not given the treatment, according to lead author Weihei Ying, PhD, a research scientist at SFVAMC and an assistant adjunct professor of neurology at the University of California, San Francisco.
The study appears in the January 1, 2007 issue of Frontiers in Bioscience.
NAD+ plays a number of essential roles in cell metabolism. One role is supporting the activity of the DNA repair enzyme PARP-1, which normally repairs cell damage from brain infection. In response to reperfusion following ischemia or brain trauma, PARP-1 is overactivated. As a result, it quickly depletes all available NAD+, in a sense its "fuel," and is unable to repair cell damage, leading to brain cell death.
In previous studies, SFVAMC researchers including Ying provided the first evidence that administration of NAD+ can completely prevent PARP-1-induced cell death in cell culture. The current study is the first to investigate NAD+ administration as a potential treatment for brain injury in animal models, and the first to demonstrate its
Contact: Steve Tokar
University of California - San Francisco