Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization
Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization
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DOI：
10.1016/s0006-8993(98)00410-7
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发表时间：
1998-09-07
期刊：
影响因子：
2.9
通讯作者：
Siddiqui, MM
中科院分区：
文献类型：
--
作者：
Yang, Y;Shuaib, A;Siddiqui, MM
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. (C) 1998 Published by Elsevier Science B.V. All rights reserved.
