Prophylactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition

被引:35
作者
Claycomb, Robert J. [1 ]
Hewett, Sandra J. [1 ]
Hewett, James A. [1 ]
机构
[1] Univ Connecticut, Ctr Hlth, Dept Neurosci, Sch Med, Farmington, CT 06030 USA
关键词
Cyclooxgenase-2; Seizures; Epileptogenesis; Kindling; Pentylenetetrazole; Epilepsy; SELECTIVE CYCLOOXYGENASE-2 INHIBITOR; NEURONAL CELL-DEATH; RAT-BRAIN; KAINIC ACID; STATUS EPILEPTICUS; COX-2; INHIBITOR; INDUCIBLE CYCLOOXYGENASE; BIOCHEMICAL PARAMETERS; MEMORY CONSOLIDATION; PILOCARPINE MODEL;
D O I
10.1111/j.1528-1167.2010.02889.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
P>Purpose: The goal of this study was to determine whether prophylactic prandial administration of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, could alter seizure generation, kindling acquisition, and/or kindling maintenance in the mouse pentylenetetrazole (PTZ) epilepsy model. Methods: Male CD-1 mice were fed ad libitum with control chow or chow formulated to deliver 30 mg/kg/day rofecoxib. After 5 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 four-point behavioral scale and COX-2 expression was assessed in brain slices from a subset of mice 3 h or 72 h after acute PTZ or following establishment of kindling. Key Findings: Hippocampal COX-2 expression was transiently upregulated 3 h after an acute PTZ-induced convulsion and returned to baseline levels within 72 h, whereas it remained elevated for at least 72 h 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. Significance: 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.
引用
收藏
页码:273 / 283
页数:11
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