Blood-pressure drug prevents epilepsy after brain injury, BGU research finds

Between one tenth and one fifth of epilepsy attacks result from serious trauma to the head.

By JUDY SIEGEL-ITZKOVICH
Pills medicine medication treatment (photo credit: Srdjan Zivulovic / Reuters)
Pills medicine medication treatment
(photo credit: Srdjan Zivulovic / Reuters)
A commonly used prescription drug for high blood pressure has been found to prevent epileptic attacks after concussion.
The findings are according to a new study on rats by researchers from Ben-Gurion University of the Negev, the University of California at Berkeley and Charité-University Medicine in Germany.
Between one-tenth and onefifth of epilepsy attacks result from serious head trauma. The researchers, who recently published their findings in the journal Annals of Neurology, found the hypertension drug losartan, commercially known as Cozaar, could prevent attacks. In addition, it may forestall further brain damage caused by seizures in those who already have epilepsy.
If independent experiments being conducted on animal models confirm it, human clinical trials could start within a few years.
“This is the first-ever approach in which epilepsy development is stopped, as opposed to common drugs that try to prevent seizures once epilepsy develops,” said Prof. Alon Friedman from BGU’s Zlotowski Center for Neuroscience. “Those drugs are administered for many years, have a limited success and involve many side effects, so we are excited about the new approach.”
The team, led by Friedman, Dr. Daniela Kaufer of University of California at Berkeley and Dr. Uwe Heinemann of the Charité, provides the first explanation of how brain injury caused by a blow to the head, stroke or infection can lead to epilepsy.
“This study for the first time offers a new mechanism and an existing, FDA-approved drug to potentially prevent epilepsy in patients after brain injuries and once they develop an abnormal blood-brain barrier,” said Kaufer.
The drug prevented seizures in 60 percent of the rats tested, when normally 100% develop seizures after this type of injury.
In the remaining 40%, they averaged about one-quarter the number of seizures typical for untreated rats. The experiment showed that administration of losartan for three weeks at the time of injury was enough to prevent most cases of epilepsy in normal lab rats in the following months.
“This is a very exciting result, telling us that the drug worked to prevent the development of epilepsy and not by suppressing the symptoms,” Friedman said.
Friedman’s main interest is in the blood-brain barrier, which normally protects the brain from potentially damaging chemicals or bacteria in the blood and prevents brain chemicals from leaking into the blood stream. He and Kaufer showed that breaking down the barrier causes inflammation and the development of epilepsy. They pinned the effect to a single protein called albumin, the most common in blood serum.
Guy Bar-Klein, a BGU doctoral student, searched a long list of drugs before discovering losartan, which is approved for high blood pressure. It worked in the rats even when delivered in their drinking water, which means that it gets into the brain through the disrupted blood-brain barrier.
At the same time, Friedman’s lab, together with the Brain Imaging Research Center at Soroka University Medical Center in Beersheba, developed a protocol to use MRI to diagnose whether the bloodbrain barrier has been breached. It allows doctors to give losartan as a preventive treatment if necessary. Friedman said that the barrier may remain open for only a few weeks after injury, so the drug should be given only for a limited period of time.