Reduction of pathological and behavioral deficits following spinal cord contusion injury with the selective cyclooxygenase-2 inhibitor NS-398
Reduction of pathological and behavioral deficits following spinal cord contusion injury with the selective cyclooxygenase-2 inhibitor NS-398
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DOI：
10.1089/089771501750170994
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发表时间：
2001-04-01
影响因子：
4.2
通讯作者：
Hulsebosch, CE
中科院分区：
文献类型：
--
作者：
Hains, BC;Yucra, JA;Hulsebosch, CE
脊髓损伤（SCI）导致运动功能丧失和异常慢性疼痛综合征的发展损伤后，继发机制包括兴奋性氨基酸的释放、炎症和脂质过氧化通过释放细胞毒性自由基损伤神经细胞。我们假设选择性抑制环氧化酶-2（考克斯-2），一种诱导性炎症介质，将减少组织损伤，并随后减少运动缺陷和损伤后慢性中枢疼痛综合征的发展。在接受T13脊髓节段脊髓挫伤损伤前15分钟，200-225-g雄性Sprague-Dawley大鼠接受载体（0.5 ml 1：1 v/v DMSO/盐水，腹膜内，n = 20）或选择性考克斯-2抑制剂NS-398（5 mg/kg DMSO/盐水v/v，腹膜内，n = 20），通过BBB量表测定运动功能，并在损伤后4周测试通过爪缩回到von Frey细丝和辐射热刺激测量的伤害性行为，同时进行脊髓组织的组织学检查和体积分析，接受NS-398的脊柱挫伤动物表现出显着的（p < 0.05）与赋形剂对照相比，运动改变减少，前肢和后肢机械异常性疼痛和热痛觉过敏减少。与溶剂对照组相比，病变节段脊髓节段的组织学检查显示病变程度降低，活组织增加。前列腺素E-2水平显着降低NS-398治疗，但没有溶剂治疗的动物损伤后12小时。这些结果支持考克斯-2在减少脊髓损伤后的病理和行为缺陷中的作用。
Spinal cord injury (SCI) results in loss of locomotor function and development of abnormal chronic pain syndromes (mechanical allodynia, thermal hyperalgesia), Following injury, secondary mechanisms including release of excitatory amino acids, inflammation and lipid peroxidation damage neural cells through release of cytotoxic free radicals, We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2), an inducible inflammatory mediator, would decrease tissue damage and subsequently reduce locomotor deficits and development of chronic central pain syndromes after injury. Fifteen minutes prior to receiving T13 spinal segment spinal cord contusion injury, 200-225-g male Sprague-Dawley rats received either vehicle (0.5 ml 1:1 v/v DMSO/saline, i.p., n = 20) or the selective COX-2 inhibitor NS-398 (5 mg/kg in DMSO/saline v/v, i.p., n = 20), Locomotor function via the BBB scale, and nociceptive behaviors measured by paw withdrawals to von Frey filaments and radiant heat stimuli were tested for 4 weeks postinjury, Histological examination and volumetric analysis of spinal cord tissue were performed concomitantly, Spinally contused animals receiving NS-398 demonstrated significantly (p < 0.05) reduced locomotor alteration and reductions in both fore- and hindlimb mechanical allodynia and thermal hyperalgesia when compared to vehicle controls. Histological examination of spinal segments at the lesion segment demonstrated reduced lesion extent and increased viable tissue when compared to vehicle controls. Prostaglandin E-2 levels were significantly lowered in NS-398-treated but not vehicle-treated animals 12 h after injury. These results support the role of COX-2 in reducing pathological and behavioral deficits after spinal cord injury.