Researcher aims to shed light on epileptic seizures and oxidative stress in the brain

LAWRENCE — More than 3 million Americans live with epilepsy, the chronic neurological disorder that brings on recurrent seizures. One of the most overlooked but damaging aspects of epileptic seizures is oxidative stress to cells in the brain.

"You need oxygen," said Craig Lunte, professor of chemistry at the University of Kansas. "Oxygen drives energy throughout your entire body. Unfortunately, oxygen also is very reactive, and some fraction of it can go into undesirable pathways that can cause damage. Oxidative stress is thought to be responsible for a whole series of diseases, to the point where aging is just considered a long-term oxidative stress event."

Lunte said that epileptic seizures caused significant oxidative stress to the brain, but that too little is known about how this occurs.

"In the case of seizures it's not quite clear why this happens," said the KU researcher. "What about a seizure causes oxidative stress, and what are the consequences of that?"

With a new $1.2 million, four-year grant from the National Institutes of Health, Lunte and collaborator Dr. Ivan Osorio from KU Medical Center are looking at focal seizures in specific brain regions such as the hippocampus, which is associated with behavior and memory. Microdialysis sampling and recording of electrocorticographic activity will shed light on chemical and electrophysiological changes in the brain tied to the seizures.

Scientists have shown that seizures lead to the formation of reactive oxygen and nitrogen species, which cause oxidative damage to DNA, lipids and proteins. Yet Lunte said that a better grasp of the role of oxidative stress in epileptic seizures was necessary before improved treatments could be developed.

"At ths point, we're trying to understand what's going on, because you can't develop treatments until you understand what to treat," he said. "Ultimately, we'd like to look at some potential interventions. There already are some out there. One of the classic ones is aspirin. It's an antioxidant. There are some compounds like that that we'll use. Hopefully, down the road we'll be able to investigate other compounds."

The biggest challenge of the work will be taking measurements of incredibly small amounts of biological material. However, devising methods to make such measurements is Lunte's area of expertise.

"Making measurements is what's fun," he said. "The big leaps in understanding and moving forward are always preceded by advances in making measurements."

To that end, Lunte will use new methods developed in his own lab to monitor formation of reactive oxygen and nitrogen species, biomarkers for DNA damage and lipid peroxidation, and neurotransmitter amino acids and catecholamines. His team also plans to look at the link between oxidative stress and neuroexcitation and how it relates to the duration and intensity of seizure episodes.