흰쥐 척수좌상에서 선택적 Cyclooxygenase-2 억제제인 NS-398 전처치의 효과
Effects of Selective Cyclooxygenase-2 Inhibitor NS-398 Pretreatment on the Rat Spinal Cord after Contusion Injury
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Abstract
Background : Secondary spinal cord injury (SCI) that follows an initial mechanical insult can exacerbate the overall damage, limit the restorative processes and eventually lead to an increased neurological deficit. We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2) may decrease the delayed cell death, and so this will contribute to decreased level of the secondary injury. Methods : The dorsal surface of the cord at the T9 level was subjected to weight drop impact using a 10 g rod. To block COX-2 activation, a selective COX-2 inhibitor (NS-398) was administered (5 mg/kg, i.p.) 15 min prior to SCI. The COX-1, COX-2, Caspase-3 and PGE2 expressions were measured by real time quantitative RT-PCR and fluorescence immunostaining. Results : Many activated caspase-3 positive cells were observed at 6 h and they increased until 72 h after SCI. The expression of COX-2 peaked at 6 h after SCI, while the COX-1 expression was unaffected. The principal cells that showed a COX-2 expression were the neurons and microglia. Pretreatment with NS-398 caused a significant decrease in the expression of prostaglandin E2 and activated caspase-3 positive cells after SCI. Conclusion : These data suggest that COX-2 is one of the main factors related with the pathologic deficits from secondary SCI.
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