Prophylactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition.
Prophylactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition.
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DOI：
10.1111/j.1528-1167.2010.02889.x
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发表时间：
2011-02
期刊：
影响因子：
5.6
通讯作者：
Hewett JA
中科院分区：
文献类型：
--
作者：
Claycomb RJ;Hewett SJ;Hewett JA
The goal of this study was to determine whether prophylatic prandial administration of rofecoxib, a selective cyclooxygenase (COX)-2 inhibitor, could alter seizure generation, kindling acquisition and/or kindling maintenance in the mouse pentylenetetrazole (PTZ) epilepsy model. Male CD-1 mice were fed ad libitum with control chow or chow formulated to deliver 30 mg/kg/day rofecoxib. After five days, mice were treated with a single dose of 40 or 55 mg/kg PTZ (acute paradigm) or 40 mg/kg PTZ delivered daily (kindling paradigm). Seizure severity was scored on a 4 point behavioral scale and COX-2 expression was assessed in brain slices from a subset of mice 3 or 72hr after acute PTZ or following establishment of kindling. Hippocampal COX-2 expression was transiently up-regulated 3hr after an acute PTZ-induced convulsion and returned to baseline levels within 72hr, whereas it remained elevated for at least 72hr after the final seizure in the kindling paradigm. Despite this increase, chronic rofecoxib treatment did not attenuate the severity of acute PTZ-induced seizures and failed to alter kindling development or maintenance. The present study demonstrates that prophylactic prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition, and does not reverse the kindled state once established.
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影响因子：
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通讯作者：
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