Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization.
Because topiramate (TPM) suppresses voltage-sensitive Na+ channels and non-N-methyl-D-aspartate (NMDA) receptors and enhances gamma-aminobutyric acid (GABA)-mediated inhibition, we tested whether it would protect against cerebral ischemia. The right middle cerebral artery (MCA) was embolized by an intra-arterial injection of autogenous thrombus. Two hours after thrombus injection, animals received intra-peritoneal injections (i.p.) of normal saline as control (n=6) or alternatively, a low- (20 mg/kg, i.p., n=6) or high-dose (40 mg/kg, i.p., n=6) of TPM. Neurological deficit was scored at 2 h and 24 h following the ischemic insult. The animals were sacrificed 24 h after ischemia and the coronal brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride (TTC) for determination of the percentage of infarct volume. Administration of TPM significantly improved the 24-h neurological deficit scores (low dose, 1.75+/-0.5; high dose, 1.17+/-0.41; p<0.05 for both doses). A reduction in the percentage of infarct volume (low dose, 22.9+/-8.9%, p=0.002; high dose 7.6+/-3.4%, p<0.001) was seen when compared to the controls (infarct size, 54.2+/-9.0%; neurobehavior score, 2. 67+/-0.52). Treatment with TPM at the higher dose induced more neuroprotection than that at the lower dose (p<0.05). Thus, treatment with TPM resulted in a dose- and use-dependent neuroprotective effect, when used 2 h after MCA embolization in a rat model of focal ischemia.
Neurology Division, Department of Medicine, University of Alberta Hospital, 2E3.13 Walter Mackenzie Health Sciences Center, Edmonton, Canada.
Y
Y
Yang
A
A
Shuaib
Q
Q
Li
M M
MM
Siddiqui
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D002536:Cerebral Arteries / Q000473:pathology; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006470:Hemorrhage / Q000188:drug therapy / Q000473:pathology; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose