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Received for publication April 6, 2004.
Revised April 30, 2004.
Accepted for publication May 12, 2004.
Non-convulsive seizures (NCS) following traumatic and ischemic brain injury are often refractory to anti-epileptic drug (AED) 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 AED treatments. Electroencephalographic (EEG) activity was recorded continuously for 24 h in freely behaving rats subjected to permanent middle cerebral artery occlusion (MCAo). Rats were treated with AEDs from one of seven different drug classes at ED50 and 2X 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 = 8.6 ± 1.9. The latency to onset of NCS was 32.5 ± 3.4 min post-MCAo with and average duration = 49.1 ± 8.2 s per event. The high dose of ethosuximide (EXM), gabapentin (GBP), fos-phenytoin (FPT), and valproate (VPA) significantly reduced the incidence of NCS (11%, 14%, 14%, and 38%, respectively), whereas midazolam (MDZ), phenobarbital (PHB), and dextromethorphan (DM) had no significant effect at either dose. Across treatment groups, the number of NCS events per animal was positively correlated with brain infarction (r = 0.352. p<0.05). AED therapy that prevented the occurrence of NCS also reduced mortality from 26% to 7%. Based on combined effects on NCS, infarction, neurologic recovery, and mortality, EXM and GBP were identified as having the best therapeutic profile.
Key words:
MCAO, anti-epileptic drug, brain injury, brain ischemia, seizure, stroke
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