Epilepsy can suddenly appear in a healthy personafter he suffers a traumatic brain injury such as a road accident. NowProf. Alon Friedman, a neurosurgeon and researcher at Ben-GurionUniversity of the Negev and colleagues at the University of Californiaat Berkeley have identified a substance that when given to ratsprevents epilepsy after brain damage. The study appears in a recentissue of the Journal of Neuroscience.
Theresearchers found that they could prevent the brain changes leading toepilepsy with a drug that blocks transforming growth factor-betareceptor (TGF-beta). They found that the hyperexcitability normallypresent after a brain trauma could be blocked by the drug. The blockersalso prevent a majority of the gene-expression changes they identifiedfollowing brain injury.
"The idea is to identify and treat only the brain injurypatients that are at risk for developing epilepsy using novel imagingapproaches. At least in the rats, it works," Friedman says.
"Because of better medical care, many victims now survivesevere traumatic brain injuries. Those with severe head injuries arethought to have a 25 to 50% chance of eventually developing epilepticseizures, yet no treatment exists to prevent such a development. Onceit develops, drugs are the only option, and even those fail to controlseizures in 30% of cases. "If the findings are confirmed in humans, aTGF-beta blocker may prevent many cases of epilepsy in accidentvictims, including soldiers or civilians who suffer brain trauma frombombing," he continues.
The results are the culmination of more than 14years of research at BGU's Brain Imaging Research Center, exploring thehypothesis that brain injury-induced epilepsy is caused by leakage ofblood components into the brain through the damaged "blood-brainbarrier" - whether caused by trauma, brain tumor, infection, meningitisor hemorrhagic/ischemic stroke.
The idea originated with Friedman, who at the time was aphysician in the Israel Defense Forces. He works with others at theresearch center - BGU's Dr. Moni Benifla, an epilepsy surgeon, and Dr.Ilan Shelef, a neuroradiologist - to detect blood-brain-barrier leakagein patients who suffered brain trauma. They follow the potentialdevelopment of epilepsy in these patients at nearby Soroka UniversityMedical Center. Friedman continues to monitor treated rats with anelectroencephalograph (EEG) to see how many go on to develop seizures.
"While observing patients, we hypothesized thatbreech of the blood-brain barrier - a sheath of tightly joined cellsthat lines the capillaries in the brain to prevent intrusion ofbacteria and potentially dangerous blood-borne molecules - somehowtriggers events that damage brain cells. In 2004, we published thefirst direct evidence in animal experiments, showing that opening theblood-brain barrier and the subsequent diffusion of blood componentsinto the brain results in epilepsy," Friedman recalls.
Friedman teamed up with Daniela Kaufer, then a HebrewUniversity graduate student, for a series of experiments that hasgradually provided support for the hypothesis and convinced many thatthis is a totally new way of looking at epilepsy. Kaufer notes thatTGF-beta blockers might also prevent further damage in those withpersistent seizures - a condition known as status epilepticus - because these non-stop seizures also open the blood-brain barrier.