February 27, 2023

Biologists Show How Brain’s Immune System Response Worsens Epilepsy

Article published by Iowa Now

University of Iowa biologists have definitively linked the brain’s immune system to epilepsy.

In a new study, the researchers lay out a chain of events that can cause seizures—the most common manifestation of epilepsy—to worsen. The sequence begins when oxidative stress in the body causes the brain’s immune system to react. That activation by the brain’s resident immune cells (called glia) triggers more severe seizures.

The findings are important because it’s the first time the brain immune system–epilepsy link has been experimentally proved. That advance should yield more precise testing and more effective medications to treat the condition.

“We have provided genetic proof that both oxidative stress and activation of the brain immune system make epilepsy worse,” says John Manak, professor in the Department of Biology and Stead Family Department of Pediatrics at Iowa and the study’s corresponding author. “This is hugely significant because our data suggest that we can now repurpose exceedingly well-tolerated anti-inflammatory compounds as well as perhaps antioxidants to help control epilepsy progression.”

The researchers clinched the brain–epilepsy connection in experiments using fruit flies. One reason they chose the insects is because fruit flies and humans share a common ancestral gene, called prickle, that when mutated, leads to seizures. The prickle gene’s involvement in epileptic seizures was determined by, among others, Alex Bassuk, pediatric neurologist and chair of the Stead Family Department of Pediatrics at Iowa, who published findings in 2008 and is a co-author on this study.