The cellular inflammatory response in human spinal cords after injury
The cellular inflammatory response in human spinal cords after injury
复制标题
DOI：
10.1093/brain/awl296
复制
发表时间：
2006-12-01
期刊：
影响因子：
14.5
通讯作者：
Weaver, Lynne C.
中科院分区：
文献类型：
--
作者：
Fleming, Jennifer C.;Norenberg, Michael D.;Weaver, Lynne C.
脊髓损伤（SCI）引起炎症反应，在脊髓内产生大量的继发性损伤，但也可能有助于其修复。人类SCI的抗炎治疗及其时机必须基于参与炎症反应的细胞类型，损伤后它们出现和数量减少的时间以及它们的作用性质的知识。使用死后的脊髓，我们评估了时间过程和分布的病理变化，浸润中性粒细胞，单核细胞/巨噬细胞和淋巴细胞，和小胶质细胞活化损伤的脊髓从患者谁是“死在现场”或谁生存的间隔长达1年后SCI。SCI引起病理变化的区域，包括急性病例中的炎症和坏死区域，以及存活时间较长的囊腔（1区），变化不太严重的区域，包括轴突肿胀、炎症和Wallerian变性（2区）和组织学完整区域（3区）。1区面积在损伤后随着时间的推移而增加，而总体损伤（1区和2区的组合大小）从损伤首次可见时的时间（1-3天）起保持相对恒定。炎性细胞的分布与1区的位置相关，有时与2区的位置相关。中性粒细胞通过表达人中性粒细胞α-防御素（防御素）而可视化，通过出血或外渗进入脊髓，在SCI后1-3天数量最多，并且在SCI后长达10天可检测到。SCI后1-3天内，大量活化的CD 68免疫反应性分支小胶质细胞和少量单核细胞/巨噬细胞出现在损伤组织中。活化的小胶质细胞，一些单核细胞/巨噬细胞和大量的吞噬巨噬细胞存在数周至数月后SCI。在整个采样间隔中，损伤的脊髓中有少量CD 8（+）淋巴细胞。分析了氧化酶髓过氧化物酶（MPO）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶（gp 91（phox））以及促炎性基质金属蛋白酶（MMP）-9的炎症细胞表达，以确定其引起氧化和蛋白水解损伤的潜力。从MPO和gp 91（phox）免疫反应性推断，氧化活性主要与中性粒细胞和活化的小胶质细胞有关。吞噬巨噬细胞MPO和gp 91（phox）表达较弱或不表达。只有中性粒细胞表达MMP-9。这些数据表明，潜在的破坏性中性粒细胞和激活的小胶质细胞，充满了氧化和蛋白水解酶，出现在SCI的最初几天，这表明抗炎的“神经保护”策略应针对防止早期中性粒细胞流入和修改小胶质细胞激活。
Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were 'dead at the scene' or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1-3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil alpha-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1-3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1-3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8(+) lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative enzymes myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate oxidase (gp91(phox)), and of the pro-inflammatory matrix metalloproteinase (MMP)-9, was analysed to determine their potential to cause oxidative and proteolytic damage. Oxidative activity, inferred from MPO and gp91(phox) immunoreactivity, was primarily associated with neutrophils and activated microglia. Phagocytic macrophages had weak or no expression of MPO or gp91(phox). Only neutrophils expressed MMP-9. These data indicate that potentially destructive neutrophils and activated microglia, replete with oxidative and proteolytic enzymes, appear within the first few days of SCI, suggesting that anti-inflammatory 'neuroprotective' strategies should be directed at preventing early neutrophil influx and modifying microglial activation.