An experimental vaccine offers promise in preventing seizures and reducing brain damage caused by stroke, according to a new study in rats. It's a long way from animal tests to the clinic, but in rat studies, a single oral dose of the vaccine provided protection for 5 months without causing any serious side effects.

The vaccine targets a structure in the brain called the NMDA receptor, which is involved in the brain damage caused by seizures and strokes. Once swallowed, the vaccine prevents damage by triggering the production of antibodies that block this receptor. Experimental drugs can block the NMDA receptors, but unfortunately, they also act on other parts of the brain, which can cause harmful side effects. Part of the vaccine's success appears to depend on its timing and its targeted attack. After the vaccine is swallowed, most of the antibodies produced remain in the blood until the early stages of a stroke or seizure begin, he said. Then large numbers of the antibodies enter the brain, but their focus is limited to NMDA receptors, not other parts of the brain.

One month after giving the vaccine to rats, During and colleagues at Jefferson and the University of Auckland in New Zealand gave a seizure-inducing injection to rats given the experimental vaccine, rats given another vaccine, and rats that had not received any vaccine. Within 10 minutes, 19 of the 25 rats that had not received the stroke vaccine began having epileptic seizures, compared with just 2 of the 9 vaccinated rats. But in one of the rats that had seizures, the vaccine appeared to have some effect, since researchers did not detect any damage to a part of the brain almost always damaged during a seizure.

In another experiment in which researchers induced a stroke in vaccinated rats and other rats, stroke was not prevented, but the brain damage was reduced by about 70% in vaccinated rats, according to the report. The vaccine did not appear to have a negative effect on the behavior of the rats.

Although exactly how long the effects of the vaccine will last is uncertain. The researchers believe that it could last for many, many months or even years. While this is good news, the long-term effects of the vaccine need to be studied to make sure that it is safe. The next step in the research will involve people, although it is too early to test the actual vaccine. Instead, hospital patients who are at high risk of having a stroke within a few days or a week will be treated with the antibodies that the vaccine produces, he said. This study should help tell whether the antibodies can prevent a stroke or at least reduce its damage in people.

Science February 25, 2000;287:1453-1460