Zeng began her studies by showing that kainate causes an increase in a marker for mTOR activity during the initial seizure; this increase returned as rats began to develop spontaneous seizures days later and suggested that rapamycin might help prevent brain changes that underlie seizures.

When Zeng gave the rats rapamycin prior to kainate, the rats still had the initial seizure, but brain cell death, new brain cells and mossy fiber sprouting all decreased, and the later spontaneous seizures were also significantly reduced. Rats that received rapamycin after the initial seizure caused by kainate still lost and gained brain cells, but they had less mossy fiber sprouting and experienced fewer subsequent seizures.

"The fact that rapamycin had beneficial effects even after the first seizure is particularly exciting, because it suggests that if similar phenomena occur in the human brain, treating patients with mTOR inhibitors after a brain injury might reduce the chances of developing epilepsy," says Wong. "This may be particularly important for the surge of veterans returning with traumatic brain injuries from Iraq and Afghanistan."

Rapamycin is currently being evaluated in clinical trials as a treatment for the brain tumors caused by TS. Wong believes the new paper will add impetus for trials to test rapamycin and other mTOR inhibitors as epilepsy prevention drugs.

wustl