Parecoxib exhibits anti-inflammatory and neuroprotective effects in a rat model of transient global cerebral ischemia

摘要

Transient global cerebral ischemia (tGCI) induces inflammation leading to secondary brain injury. Data suggested that cyclooxygenase-2 (COX-2) is involved in the occurrence and development of inflammatory reaction after reperfusion; however, the effectiveness of a highly selective COX-2 inhibitor, parecoxib, to counteract tGCI remains to be determined. Thus, the aim of this study was to investigate the potential protective actions of parecoxib in a rat model of tGCI and the role inflammation plays in this disorder. Adult male Sprague-Dawley rats were administered parecoxib 10 or 20 mg/kg intraperitoneally (ip) at 5 min, 24 or 48 hr after tGCI. Control rats received an equal volume of 0.9% saline. The rat model of tGCI was established using the method of bilateral common carotid artery occlusion combined with arterial hypotension. The following parameters were measured: Neurological Severity Score, morphological changes in the hippocampal CA1 region, Evans blue (EB) extravasation, brain water content, levels of matrix metalloproteinase-9 (MMP-9), zonula occludens-1 (ZO-1), neuronal apoptosis, the protein expression of Bcl-2, Bax, COX-2, prostaglandin E2 (PGE(2)), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha). Parecoxib treatment significantly improved neurological function and morphological defects in the hippocampal CA1 region, reduced levels of COX-2, PGE(2), IL-1 beta, and TNF-alpha. In addition, parecoxib attenuated brain edema and BBB destruction as evidenced by increased ZO-1 expression and decreased MMP-9 expression. Further, parecoxib reduced neuronal apoptosis via diminished protein expression of Bax and enhanced expression of Bcl-2.