VCU news

By Robert DeLorenzo and Lorraine Cichowski

RICHMOND, Va. - Long-lasting changes in calcium levels in the brain�s neurons following a stroke may play a role in both the onset and recurrence of epilepsy, according to researchers at the Virginia Commonwealth University Medical Center.

The findings, reported in the February issue of Cell Calcium, demonstrate that significant alterations in calcium levels occur in association with stroke-induced epilepsy and last for an extended period, advancing scientific knowledge of how normal tissue in the central nervous system is transformed into brain tissue prone to spontaneous, recurrent seizures. The article was published early online.

"Stroke is one of the leading causes of acquired epilepsy, yet little is known about the underlying basic mechanisms leading to stroke-induced epilepsy," says Dr. Robert J. DeLorenzo, professor of neurology and a world-known expert in epilepsy. "Discovering these links between stroke and prolonged alterations in calcium levels opens a new horizon for research into epilepsy because calcium plays such a pivotal role as a messenger molecule in neurons.

"If we can understand the role that calcium plays in causing epilepsy, we can develop drugs to help block it."  

Epilepsy is one of the most-common neurological disorders. The disease, which makes people susceptible to seizures, affects more than 2.3 million Americans and 50 million people worldwide, according to the National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/epilepsyweb/benchmarks.htm). In some cases, epilepsy is inherited, and sometimes doctors cannot find a cause.  About half of epilepsy cases, however, have a known cause - stroke being the most common one -- and are referred to as "acquired epilepsy." According to the Epilepsy Foundation, 22 percent of all stroke patients will develop epilepsy.

DeLorenzo's laboratory developed a novel in vitro model of stroke-induced epilepsy in 2000 as a powerful tool to study molecular changes in the brain, particularly alterations in calcium levels. The system exposes brain tissue of rats to the chemical substance, glutamate, to produce a brain injury similar to that caused by stroke.

Using that model of stroke-induced epilepsy, the VCU researchers in this most-recent study measured calcium levels in healthy brain tissue and in brain tissue injured by an induced stroke. They found that levels of calcium in epileptic neurons were nearly three times higher five days after injury, compared with levels of calcium in neurons from healthy brain tissue. The calcium levels in the epileptic neurons dropped after treatment with an experimental epilepsy drug. However, the levels did not drop to levels seen in the healthy neurons. The data indicated that induction of epilepsy in the model caused a permanent elevation of calcium levels for the life of the neurons in the culture.

DeLorenzo first reported the link between calcium and stroke-induced epilepsy in 2002.

The Department of Neurology's epilepsy center at the VCU Medical Center has been studying the causes of epilepsy for 15 years and has compiled one of the world�s largest databases on status epilepticus, a life-threatening form of the disease.

The current research was supported by grants from the National Institute of Neurological Disorders and Stroke, Epilepsy Program Project, Milton L. Markel Alzheimer�s Disease Research Fund and Sophie and Nathan Gumenick Neuroscience Research Fund.