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Tree covered with moss

Brainwide spread of seizures linked to specific cell type, new study shows

New Stanford Medicine research shows that a type of nerve cell called mossy cells play a key role in seizures in temporal lobe epilepsy.

In the United States, there are more than 20 drugs on the market for treating epilepsy. But between 30 and 40 percent of the time, these drugs fail to halt seizures, resulting in a chronic vulnerability to sometimes ultra-frequent seizures and consequent prohibitions on concentration-critical activities such as driving a car, neuroscientist Ivan Soltesz, PhD, told me.

Now, researchers led by Soltesz have pointed epilepsy research in a promising new direction by nailing down the key role of a unique class of brain cells, called mossy cells, in the most common form of the disorder, temporal lobe epilepsy. The study appears in Science.

Epilepsy is a powerful disruptor of human well-being. From my news release on the study:

Epileptic seizures are sometimes described as an electrical storm in the brain. These storms typically begin at a single spot in the brain, called the focus, where nerve cells — for reasons that remain unclear — begin repeatedly firing in synchrony. All too often they spread from the focus to widespread areas throughout the brain, a process called generalization. It’s this brain-wide spread of hyperactivity that causes the classic behavioral symptoms of epileptic seizures, such as loss of consciousness, convulsions and disordered thinking.

Soltesz and his colleagues have shown that a single set of nerve cells -- the mossy cells -- controls the spread of temporal lobe seizures throughout the brain. Activating mossy cells doesn’t stop the initial generation of a seizure at the focus, but can prevent a seizure from spreading. This means that new classes of drugs aimed at stimulating mossy-cell activity could diminish or eliminate symptomatic seizures and, potentially, restore lifestyle options that had been put on hold by those affected.

The discovery of mossy cells’ function resolves a mystery that has perplexed neuroscientists for decades. It’s known that these cells innervate both excitatory and inhibitory nerve cells in the hippocampus, a key brain structure that projects to widespread areas throughout the brain. The hippocampus is critical to our ability to remember recent events (as in, what did we have for breakfast yesterday?) and spatial configurations (like, where we parked the car). So, the overall effect of mossy-cell activity on hippocampal function and on the spread of seizures from focal points within the hippocampus (where most temporal lobe seizures originate) to distant parts of the brain was unknown.

Mossy cells are extremely delicate and, it’s known, depleted in the brains of people who have chronic drug-resistant temporal lobe epilepsy. These people are at heightened risk for memory losses, mood disorders and early death. It could turn out that finding ways to preserve and boost mossy-cell function will yield wide-ranging improvements not only in seizure likelihood but also memory, mood and maintenance of physical health among a large group of people who until now have faced tough odds.

Photo by Jamie Hagan

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