Epilepsy can suddenly appear in a healthy person
after he suffers a traumatic brain injury such as a road accident. Now
Prof. Alon Friedman, a neurosurgeon and researcher at Ben-Gurion
University of the Negev and colleagues at the University of California
at Berkeley have identified a substance that when given to rats
prevents epilepsy after brain damage. The study appears in a recent
issue of the Journal of Neuroscience.
researchers found that they could prevent the brain changes leading to
epilepsy with a drug that blocks transforming growth factor-beta
receptor (TGF-beta). They found that the hyperexcitability normally
present after a brain trauma could be blocked by the drug. The blockers
also prevent a majority of the gene-expression changes they identified
following brain injury.
"The idea is to identify and treat only the brain injury
patients that are at risk for developing epilepsy using novel imaging
approaches. At least in the rats, it works," Friedman says.
"Because of better medical care, many victims now survive
severe traumatic brain injuries. Those with severe head injuries are
thought to have a 25 to 50% chance of eventually developing epileptic
seizures, yet no treatment exists to prevent such a development. Once
it develops, drugs are the only option, and even those fail to control
seizures in 30% of cases. "If the findings are confirmed in humans, a
TGF-beta blocker may prevent many cases of epilepsy in accident
victims, including soldiers or civilians who suffer brain trauma from
bombing," he continues.
The results are the culmination of more than 14
years of research at BGU's
Brain Imaging Research Center, exploring the
hypothesis that brain injury-induced epilepsy is caused by leakage of
blood components into the brain through the damaged "blood-brain
barrier" - whether caused by trauma, brain tumor, infection, meningitis
or hemorrhagic/ischemic stroke.
The idea originated with Friedman, who at the time was a
physician in the Israel Defense Forces. He works with others at the
research center - BGU's Dr. Moni Benifla, an epilepsy surgeon, and Dr.
Ilan Shelef, a neuroradiologist - to detect blood-brain-barrier leakage
in patients who suffered brain trauma. They follow the potential
development of epilepsy in these patients at nearby Soroka University
Medical Center. Friedman continues to monitor treated rats with an
electroencephalograph (EEG) to see how many go on to develop seizures.
"While observing patients, we hypothesized that
breech of the blood-brain barrier - a sheath of tightly joined cells
that lines the capillaries in the brain to prevent intrusion of
bacteria and potentially dangerous blood-borne molecules - somehow
triggers events that damage brain cells. In 2004, we published the
first direct evidence in animal experiments, showing that opening the
blood-brain barrier and the subsequent diffusion of blood components
into the brain results in epilepsy," Friedman recalls.
Friedman teamed up with Daniela Kaufer, then a Hebrew
University graduate student, for a series of experiments that has
gradually provided support for the hypothesis and convinced many that
this is a totally new way of looking at epilepsy. Kaufer notes that
TGF-beta blockers might also prevent further damage in those with
persistent seizures - a condition known as status epilepticus - because these non-stop seizures also open the blood-brain barrier.