Abstracts

Rationale: There is an urgent need to develop treatment strategies to protect the developing brain from seizure-induced injury. There is growing evidence that topiramate (TOP) is a robust candidate as a neuroprotective agent. The goal of our study was to investigate the neuroprotective effect of early and prolonged topiramate administration following status epilepticus (SE) in rats.Methods: SE was induced in young adult male rats (n=16) using lithium-pilocarpine while control rats (n=16) were treated with normal saline. Experimental rats gradually developed stage 5 seizures. To produce a uniform degree of brain injury all animals had the status epilepticus stopped after 2 hours with an intravenous injection of diazepam (5 mg/kg). Control rats also received diazepam. Starting one hour after the diazepam injection rats were randomized to topiramate or normal saline injections and formed four groups: SE-TOP, SE-NS, SHAM-TOP, and SHAM-NS. A dose of 80 mg/kg/day (divided twice daily) of topiramate was given intraperitoneum to the topiramate groups whereas equal volume injections of saline were given to the normal saline groups. Following the treatment phase rats underwent testing in the water maze. Rats were trained initially with a stable platform location for four days, followed by one trial without the platform. The platform location was then switched and rats were trained for two days, followed by a second platform switch and two additional days of training. Results: All four groups improved in water maze performance over the four testing days. There was a significant difference in the four groups (p<0.0001) with both sham groups performing better than the SE groups. There was a significant difference between SE-NS and SE-TOP groups (p<0.0001) with the rats receiving TOP performing better than the NS group. In the switch test the SE-TOP group also performed better than the SE-NS after the first switch (p=0.001).Conclusions: Topiramate-treated rats fared better than normal saline-treated rats following SE in a test of spatial memory performance. These results demonstrate that topiramate has a beneficial effect on spatial learning when the drug is administering following status epilepticus. Source of funding is a grant from Johnson & Johnson.