Post-treatment with rapamycin does not prevent epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy.
Approximately 30% of all epilepsy cases are acquired. At present there is no effective strategy to stop epilepsy development after the precipitating insult. Recent data from experimental models pointed to the mTOR pathway, which can be potently inhibited by rapamycin. However, data on the antiepileptic and antiepileptogenic properties of rapamycin are conflicting. Therefore, we tested whether rapamycin post-treatment influences epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy in rats. Animals were treated with rapamycin (6mg/kg) or vehicle daily for 2 wks, beginning 24h after stimulation. Sham-operated animals were treated with rapamycin or vehicle but were not stimulated. Animals were video-EEG monitored to detect spontaneous seizures. Animals were sacrificed 4 wks later and brains were collected for Timm staining. There were no significant differences in the number of stimulated rats developing epilepsy; latency to first spontaneous seizure; number of seizures, or seizure frequency in epileptic animals. The area occupied by mossy fibers was significantly increased in stimulated vs. sham-operated animals but was not different in animals treated with rapamycin vs. vehicle. Collectively, our data suggest that the antiepileptic or antiepileptogenic action of rapamycin is not a universal phenomenon and might be limited to certain experimental models or experimental conditions.
Laboratory of Epileptogenesis, The Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
Anna
A
Sliwa
Gabriela
G
Plucinska
Joanna
J
Bednarczyk
Katarzyna
K
Lukasiuk
D000679:Amygdala; D000818:Animals; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D020123:Sirolimus / Q000008:administration & dosage* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus