New research in mice suggests that an antioxidant compound called dehydroascorbic acid, the precursor to vitamin C, can cross the critical barrier between the bloodstream and the brain and reduce the damage caused by a stroke, reports HealthScoutNews.
The findings appear in the September 25 issue of the Proceedings of the National Academy of Sciences.
Currently, approximately 750,000 Americans suffer a stroke every year, and almost 160,000 of those attacks are fatal. Ischemic strokes make up about 83 per cent of all stroke cases.
There is only one existing therapy available for patients who have suffered an ischemic stroke: tissue plasminogen activator (or tPA), which can only be given only after brain-imaging scans confirm a stroke.
When the blood supply is cut off to brain tissues during an ischemic stroke, restoring blood flow quickly is critical. But paradoxically, the return of oxygenated blood triggers an inflammatory response that can kill partially damaged cells.
One of the factors that play a role in this inflammation is the release of harmful free radicals by the body's immune cells. Antioxidants, like vitamin C, are thought to control the production of free radicals. But vitamin C cannot cross the blood-brain barrier that normally protects the brain from harmful compounds.
Now researchers at Columbia University have shown that dehydroascorbic acid (DHA), the oxidised form of vitamin C, can cross the blood-brain barrier in an mouse model of ischemic stroke. Once it crosses the blood-brain barrier, the DHA is converted to vitamin C. Moreover, mice treated with DHA appear to be better protected from the brain damage caused by stroke.
First, the researchers caused ischemic stroke in mice and injected DHA intravenously into the animals. Autopsies of the mice revealed that, unlike vitamin C, DHA sneaked past the blood-brain barrier.
The next step was testing the effect of the DHA. The researchers induced stroke in a group of mice, giving some of them a range of concentrations of DHA, while others received another antioxidant or a placebo. Animals received the treatments either 15 minutes or three hours after the stroke, and were monitored for the severity of brain tissue damage, cerebral blood flow, neurological impairment and mortality.
DHA appeared to have a significant effect. On average, mice that received DHA 15 minutes after their stroke showed a six-fold reduction in brain tissue damage and exhibited less neurological impairment than mice that received the other antioxidant or the placebo. The protective effect appeared to extend also to mice treated with DHA three hours after the stroke.
Mice that received the highest concentration of DHA showed a nine-fold reduction in brain damage compared to animals that received a placebo. These mice also showed the least neurological impairment and doubled their cerebral blood flow 24 hours after the stroke. Animals that received the highest dose of DHA were also the least likely to die after a stroke.
"We finally have an antioxidant that's actively transported across the blood-brain barrier," says senior investigator Dr. E. Sander Connolly, Jr., an associate professor of neurological surgery. "The advantage of this is that it appears to be so safe and has a long treatment window."
"It fits with a lot of literature showing that antioxidant treatment can be good for at least animal models of stroke," notes John Wilson, a professor of physiology at the University of Western Ontario who is familiar with the study. "I was really impressed that they could give the DHA three hours after the stroke and still see smaller [stroke], decreased mortality and less neurological deficits on the behavioural tests. That could be potentially clinically applicable."
However, cautions Dr. Wilson, "there is a lot of literature of not just positive effects, but also negative effects of giving large doses of vitamin C and large doses of DHA." He says that in older studies, massive doses of DHA were used to destroy the pancreas in animals in order to cause diabetes.
He also points out that the DHA solution used in this study was 95 per cent pure, and the effect of contaminants in the remaining 5 per cent is unclear. However, Connolly says that this solution is for use only in mice, and that any solutions made for humans would be different.
Drs. Connolly and Wilson agree that the need for new ischemic stroke therapies is urgent. "The suffering from this disease is horrible," says Dr. Connolly. "And the complication rates from tPA are not insignificant."
"Essentially, we now have a vitamin that's very safe that can be given to protect animals from stroke," says Connolly. "The question is, can we now give that same vitamin to humans to protect them from stroke?"
The team is now planning studies to test DHA in animals whose neurological systems more closely resemble the human brain.