BioEd Online

Experiments on immature rats' brains suggest that treating epileptic children with benzodiazepine drugs could do more harm than good, scientists in France have claimed. They have found that the neurotransmitters unlocked by these drugs cause changes in brain chemistry that actually promote epileptic activity.

Anticonvulsant benzodiazepines are a last-ditch treatment used to stop seizures in both infants and adults. Some medical experts think that the electrical activity associated with seizures can change brain networks, making them more susceptible to future epileptic activity.

So understanding the chemistry of seizures might lead to drugs that can counteract epilepsy's development, says Yehezkel Ben-Ari, a neuroscientist at the Mediterranean Institute of Neurobiology in Marseille.

His team studied the electrical and chemical activity of brains removed from baby rats. They were particularly interested in the hippocampus, a part of the brain important in epileptic seizures.

The researchers found that the neurotransmitter gamma-aminobutyric acid (GABA) triggers rapid electrical signalling in the immature hippocampus - a hallmark of epileptic seizures. Benzodiazepine drugs enhance the action of this neurotransmitter.

Conversely, drugs that block nerve cells' GABA receptors seemed to prevent repeated seizures in the rats' brains. The team's results are published this week in Neuron¹.

A lack of options

About a third of the 2.7 million epileptics in the United States are 17 or younger. Treatments include drugs and surgery. Recent studies have also suggested that a high-fat, low-carbohydrate diet reduces seizures in children with intractable epilepsy.

But therapy often fails. "Sixty to seventy percent of kids with epilepsy don't have effective treatment options," says Peter van Haverbeke, a spokesman for the Epilepsy Foundation in Landover, Maryland.

Although benzodiazepine treatment is relatively rare, Ben-Ari says that medics should still look more closely at the use of drugs that enhance GABA signalling. He speculates that too much GABA signalling in the very young can make chloride ions build up in immature neurons, predisposing them to further epilepsy.

Ben-Ari stresses that the adult brain is probably very different. There, GABA inhibits the fast electrical signalling associated with adult epilepsy. This may be connected with changes in the way chloride ions are transported in and out of neurons as the brain grows older, he explains.

Libor Velisek, a neuroscientist at the Albert Einstein College of Medicine in New York, suggests that doctors should also investigate whether pregnant women taking benzodiazepines could be predisposing their children to epilepsy: "I think that this may be an important issue," he says.

Ben-Ari and his team are now studying the effects of benzodiazepines on neurons, hoping to find out if the drugs do indeed promote epileptic signalling.