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Unsuspected brain cells may cause epilepsy

January 4th, 2011 by robert mckee
The roots of epilepsy lie in an often-overlooked type of brain cell and not in the neurons as was previously thought, a new study claims. The US-based researchers hope their findings will lead to more appropriate treatments for the condition.

Epilepsy is a syndrome that arises when a brain chemical, called glutamate, stimulates neurons to start firing wildly and uncontrollably, sometimes resulting in seizures or loss of consciousness. Current treatments are aimed at slowing down brain function to reduce the neuronal firing, but these have unwelcome side effects, such as drowsiness.

Neurologists generally believe that epilepsy causes the production of abnormal cells called reactive astrocytes - oversized, bloated, star-shaped cells that no longer function properly in their "housekeeping" role of maintaining the brain's optimum chemical environment.

So Maiken Nedergaard, at the University of Rochester Medical Center, New York, and colleagues decided to take a closer look at the role of astrocytes in epilepsy. The team induced epilepsy in rats using five different known methods, for example lowering the level of brain calcium. They then blocked synaptic activity completely using the neurotoxin tetrodotoxin (TTX), which meant there was no neural firing and therefore no seizures in the rats.

"To our great surprise, we found that there was an increase in reactive astrocytes in all five models, which could not have been caused by over-firing of the neurons as expected - because there had been no neural firing," says Nedergaard.

"And the reactive astrocytes were producing excessive glutamate in the rats. It turns out that reactive astrocytes trigger epilepsy, and not the other way around," she concludes.

Hammering away

Astrocytes are a major type of brain cell, but because they are not involved in electrical activity within the brain, they have been studied relatively little.

Donald Weave, president of Epilepsy Canada, agrees. The role of glial cells, the cells that surround and support neurons, in epilepsy and neurology "has been understudied", he says. "We have been hammering away at the same old approaches for years and so a new way in with astrocyte involvement would be very useful."

The cell type is found in larger proportion - and with more "points" on the star-shaped cell - in animals with higher brain function. Monkeys have roughly the same number of astrocytes as neurons in their brains, whereas humans have 10 times as many astrocytes as neurons.

Recently, more has been discovered about the importance of these cells and the role they play in diseases, from stroke to Alzheimer's.

Blood to brain

One of the roles of these "housekeeper" cells is to mop up excess glutamate. But Nedergaard reports that when the cells become abnormal, they appear to produce detrimental amounts of the chemical. "We need to find a treatment that controls the release of glutamate or inhibits reactive astrocytes. At the moment, the drugs that could do this are not able to pass the blood-brain barrier," she says.

"It's very important, because right now we are treating children - who are in education and still learning - with drugs that slow down their synaptic activity and brain function, which is very bad," she told New Scientist.

The researchers used the rat models to analyse three drugs commonly used to treat epilepsy. They found that in addition to slowing neural firing, the drugs reduced the type of chemical signalling that causes astrocytes to release glutamate. "This may be why they work," Nedergaard suggests.

Ley Sander, at the UK's National Society for Epilepsy, comments: "This a most interesting study as it suggests that astrocytes may be involved in the initiation and propagation of epileptic discharges. This is, however, based in animal models and it remains to be seen if this is a true reflection of what happens in the human brain at the time of a seizure. If it is, then new avenues for the pharmacological treatment of epilepsy will be opened."

And a spokesperson from UK-based charity Epilepsy Action, adds: "We welcome any research into epilepsy, particularly research that is related to a cure for epilepsy, as opposed to suppressing seizures."

Journal reference: Nature Medicine (DOI: 10.1038/nm1277)


 
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Tags: neurological disorders, Epilepsy, seizures, Alzheimer's


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