PT  - JOURNAL ARTICLE
AU  - A. J. Williams
AU  - F. C. Tortella
AU  - X. M. Lu
AU  - J. E. Moreton
AU  - J. A. Hartings
TI  - Antiepileptic Drug Treatment of Nonconvulsive Seizures Induced by Experimental Focal Brain Ischemia
AID  - 10.1124/jpet.104.069146
DP  - 2004 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 220--227
VI  - 311
IP  - 1
4099  - http://jpet.aspetjournals.org/content/311/1/220.short
4100  - http://jpet.aspetjournals.org/content/311/1/220.full
SO  - J Pharmacol Exp Ther2004 Oct 01; 311
AB  - Nonconvulsive seizures (NCSs) after traumatic and ischemic brain injury are often refractory to antiepileptic drug therapy and are associated with a decline in patient outcome. We recently characterized an in vivo rat model of focal brain ischemia-induced NCS and here sought to evaluate potential pharmacological treatments. Electroencephalographic activity was recorded continuously for 24 h in freely behaving rats subjected to permanent middle cerebral artery occlusion (MCAo). Rats were treated with an antiepileptic drug from one of seven different drug classes at ED50 and 2× ED50 doses (as reported in other rat seizure models), delivered as a single i.v. injection 20 min post-MCAo. Vehicle-treated rats (n = 9) had an 89% incidence of NCS with an average number of NCS of 8.6 ± 1.9. The latency to onset of NCS was 32.5 ± 3.4 min post-MCAo with an average duration of 49.1 ± 8.2 s/event. The high doses of ethosuximide, gabapentin, fos-phenytoin, and valproate significantly reduced the incidence of NCS (11, 14, 14, and 38%, respectively), whereas midazolam, phenobarbital, and dextromethorphan had no significant effect at either dose. Across treatment groups, there was a low but significant correlation between the number of NCS events per animal and volume of brain infarction (r = 0.352). Antiepileptic drug therapy that prevented the occurrence of NCS also reduced mortality from 26 to 7%. Based on combined effects on NCS, infarction, neurological recovery, and mortality, ethosuximide and gabapentin were identified as having the best therapeutic profile. The American Society for Pharmacology and Experimental Therapeutics