Vaccine Strategy for Stroke Damage

When it's healthy, the brain protects itself from the riffraff that circulates in the bloodstream by means of a guard membrane. This so-called blood-brain barrier keeps out uninvited guests--until a stroke or other trauma breaks it down. Now, researchers working with rats report they can take advantage of the barrier's temporary permeability to slip potentially helpful compounds into the brain immediately after a stroke, thus limiting brain damage.

Strokes and other head traumas damage the brain beyond their site of origin by exciting nearby neurons to death. Drugs can reduce stroke damage by blocking the NMDA receptor, which receives the excitatory signals. But the drugs have to be given almost immediately, and many stroke victims don't receive treatment until hours too late.

Now a team of neuroscientists has shown that a vaccine can help--at least in laboratory animals--by immunizing rats against the cell death caused by stroke and severe seizures. Matthew During of the University of Auckland in New Zealand and Thomas Jefferson University in Philadelphia vaccinated the animals with a virus that had been genetically engineered to contain part of the NMDA receptor. Antibodies to the NMDA receptor, they theorized, would remain outside of the brain until a stroke or other abuse caused the blood-brain barrier to break down; then they would rush in and block the receptor just as drugs do.

After 1 to 3 months, in which time the rats built up antibodies, the researchers induced seizures or strokes. If untreated, 68% of rats had severe seizures that killed brain cells, they report in the 25 February Science. In contrast, only 22% of the vaccinated animals seized. Mock strokes destroyed large portions of control animals' brains, but in vaccinated animals, the lesions were 70% smaller.

The protection against stroke damage conferred by the antibodies "was as good as could possibly be expected," says neuroscientist Brian Meldrum of King's College Institute of Psychiatry in London. But the technique could pose dangers to humans. Neuroscientist James McNamara of Duke University in Durham, North Carolina, cautions that "immunizing people with neural antigens might have unwanted effects," including encephalitis or learning disruptions.

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