快猫短视频

Damage limitation

A vaccine could protect you against strokes and epilepsy

THE devastating effects of strokes and epileptic seizures could soon be
minimised by an oral vaccine. Just as children are routinely immunised against
polio and diphtheria, so adults might be vaccinated in middle age to protect
them from brain damage, say researchers in New Zealand and the US.

Strokes and seizures trigger a cascade of events that lead to brain damage.
During a stroke, the region around the injury becomes awash with the
neurotransmitter glutamate. This in turn unleashes high levels of calcium, which
kills brain cells. 快猫短视频s have tried to interrupt this cascade with drugs,
but the doses needed are so high that they cause serious side effects such as
motor problems or psychosis.

So Matthew During, a neuroscientist at Thomas Jefferson University in
Philadelphia, and his colleagues have now tried a different strategy. They want
to block a glutamate receptor in the brain鈥攖he NMDA (N
-methyl-d-aspartate) receptor鈥攂y getting patients to make antibodies
against it.

The beauty of using antibodies is that they spring into action only when
they鈥檙e needed, says During. When an animal is healthy, the blood-brain barrier,
a molecular fence around the brain, keeps antibodies out. But when the brain is
being injured, such as during a seizure, the barrier gets leaky and some
antibodies can sneak through. 鈥淛ust enough get across to stop epilepsy,鈥 says
During.

The team made an oral vaccine by putting cloned DNA from a mouse NMDA
receptor gene inside a harmless virus. This vaccine triggers the production of
antibodies that stick to the NMDA receptors and stop glutamate binding to them.
The researchers think the body will retain the ability to make the antibodies
indefinitely.

Nine rats were given the experimental vaccine, while two control groups got
either no vaccine or one that targeted an unrelated marker protein. One month
later, the researchers induced epileptic fits in all the rats. An independent
observer noted the symptoms of each of the rats, ranging from immobility and
staring to 鈥渨et-dog shakes鈥.

Nineteen of the 25 control rats showed behavioural signs of epilepsy, while
only two of the NMDA receptor-vaccinated rats did. And only control rats showed
neurological damage in their brains. So vaccination can not only produce
resistance to seizure but also protect against resulting brain injury, the
researchers say.

They also induced strokes in a different group of 10 rats, which had been
vaccinated five months previously. Three days later, they found that NMDA
receptor-vaccinated rats had suffered 70 per cent less brain damage than the
controls.

Brian Meldrum of the Institute of Psychiatry in London says the work is
exciting, but cautions that little is known about how the antibodies will affect
the brain. 鈥淭he antibodies might get in quite diffusely and get in over a long
period of time,鈥 he says. 鈥淲e don鈥檛 know what damage that could cause.鈥 During鈥檚
team hope to start human trials of the vaccine within the next two years.

  • Source:
    Science (vol 287, p 1453)

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