The systemic inflammatory response after spinal cord injury damages lungs and kidneys
The systemic inflammatory response after spinal cord injury damages lungs and kidneys
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DOI：
10.1016/j.expneurol.2008.01.033
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发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Weaver, Lynne C.
中科院分区：
文献类型：
--
作者：
Gris, Denis;Hamilton, Eilis F.;Weaver, Lynne C.
脊髓损伤（SCI）引发了一个很好的特点，急性，局部炎症导致继发性损害的病变部位。另一个很少被认识到的问题可能是循环炎性细胞的激活，这可能会损害脊髓外的组织。我们用严重的夹压法研究了这个问题。我们研究了SCI后的全身炎症及其对肺和肾的影响，作为SCI功能障碍的大鼠。这些器官是SCI后常见的早期并发症。SCI后2-24 h，循环中性粒细胞（尤其是未成熟细胞）数量显著增加3-10倍。流式细胞术实验表明，SCI短暂激活这些中性粒细胞，导致增加的氧化反应，佛波肉豆蔻酸在SCI后2小时，然后，从4-24小时，中性粒细胞反应较低。SCI后2-8小时，神经元寿命增加（凋亡减少30-50%）。免疫组织化学分析表明，中性粒细胞侵入肺和肾（2小时-7天后SCI）和更多的吞噬巨噬细胞在肺（12小时，3天后SCI）。脊髓损伤后12 h ~ 7 d，肺、肾组织中髓过氧化物酶和基质金属蛋白酶-9活性升高。考克斯-2表达增加，脂质过氧化反应也发生在这一时期。通过兴奋性毒性使君子酸注射诱导局部脊髓损伤的对照实验证实，SCI本身足以引发全身炎症和器官损伤。总之，SCI动员和激活中性粒细胞，然后迁移到内脏器官，这种现象与众所周知的进入脊髓损伤部位的现象平行发生。SCI的全身炎症反应应成为SCI治疗新策略的目标。(C)2008年爱思唯尔公司All rights reserved.
Spinal cord injury (SCI) triggers a well characterized, acute, local inflammation leading to secondary damage at the lesion site. Another little recognized problem may be the activation of circulating inflammatory cells that potentially damage tissues outside the cord. We investigated this problem using severe clip-corn press ion We studied systemic inflammation after SCI and its effects on lungs and kidneys, as dysfunction of SCI in rats. these organs is a frequent, early complication after SCI. From 2-24 h after SCI, the number of circulating neutrophils (especially immature cells) significantly increased by 3-10 fold. Flow cytometry experiments revealed that SCI transiently activates these neutrophils, causing increased oxidative responses to phorbolmyristic acid at 2 h after SCI: then, from 4-24 h, the neutrophils were less responsive. Neutrophil longevity was increased (30-50% decrease in apoptosis) at 2-8 h after SCI. Immunohistochemical analyses demonstrated the invasion of neutrophils into lungs and kidneys (2 h-7 d after SCI) and more phagocytic macrophages in lungs (12 h, 3 d after SCI). Myeloperoxidase and matrix metal loproteinase-9 activity in lung and kidney homogenates increased (12 h-7 d after SCI). Expression of COX-2 increased and lipid peroxidation also occurred within this time. Control experiments inducing local cord damage by excitotoxic quisqualate injection verified that SCI per se is sufficient to trigger systemic inflammation and organ damage. In summary, SCI mobilizes and activates neutrophils that then migrate into visceral organs, a phenomenon occurring in parallel with their well-known entry into the cord injury site. The systemic inflammatory response to SCI should be targeted in the development of new therapeutic strategies to treat SCI. (C) 2008 Elsevier Inc. All rights reserved.