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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.
The 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.
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