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A surprising finding about seizures

Holmes found that suppressing post-seizure signals increased brain damage.

By Boer Deng

A seizure can be a scary thing. Brain cells fire freely, causing random muscles to twitch and brain activity to spike. When a seizure lasts more than 30 minutes, a situation known as status epilepticus (SE), severe brain damage can result from cell loss and abnormal neuronal growth. SE affects 20% of people with epilepsy, and the damage can continue even after the seizure ends.

That's why Gregory Holmes, M.D., is studying new treatments to reduce damaging activity in the brain during and after SE. In a recent paper in the journal Seizure, he reported an unexpected finding.

Brain: "One of the techniques [for post-SE treatment] is to shut the brain down" using drugs, Holmes explains, in order to prevent neurons from being able to refire and trigger another seizure. But some patients don't respond immediately to the drugs, and, even in those who do, the treatment doesn't stop all brain activity. Neurons deep in the hippo-campus-the part of the brain involved in long-term memory and the limbic system-keep firing, which may continue to cause brain damage. Knowing this, Holmes and his colleagues hypothesized that if these electrical signals were also suppressed, perhaps SE-related brain damage could be lessened.

To test their hypothesis, they gave controlled doses of a drug called tetrodotoxin (TTX) to adult rats, post-SE, to stop all electrical activity in the brain. TTX works by blocking neurons from firing. Much to their surprise, Holmes and his team found that two weeks after treatment, the brains of the TTX-treated rats had more damage than the brains of untreated rats-a control group that received saline infusions. The TTX-treated brains showed increased cell loss and abnormal neuronal growth, known as mossy fiber sprouting.

Holmes is now rethinking the direction of future studies; he believes a better approach might be to use a cocktail of drugs to prevent cell death and abnormal neuron growth. Holmes's paper was the first published demonstration of the effects of suppressing all electrical brain activity after SE. And although his results turned out to be negative, they're likely to lead to some positive effects for people who have epilepsy and others who suffer from SE.

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