Evolution of Inflammation and White Matter Injury in a Model of Transient Focal Ischemia
Evolution of Inflammation and White Matter Injury in a Model of Transient Focal Ischemia
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DOI：
10.1097/nen.0b013e3181c3ce6c
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发表时间：
2010-01-01
影响因子：
3.2
通讯作者：
Schlichter, Lyanne C.
中科院分区：
文献类型：
--
作者：
Moxon-Emre, Iska;Schlichter, Lyanne C.
缺血性中风后，有一个长期的炎症反应和继发性损伤阶段，这比急性神经毒性更容易治疗。令人惊讶的是，很少有人知道炎症和白色物质损伤之间的时间和空间关系。在这里，我们定量的发展白色物质损伤，炎症，和胶质细胞界在短暂缺血后1，3，7天，在大鼠纹状体使用免疫组织化学。定量分析表明，髓鞘碱性蛋白染色减少和受损髓鞘碱性蛋白染色增加开始于核心，符合中性粒细胞浸润，并随着时间的推移向外进展。轴突损伤（即淀粉样前体蛋白的积累）开始于病变的边缘，与大量的小胶质细胞/巨噬细胞活化一致，并进展到核心。在7天内，活化的小胶质细胞/巨噬细胞仅在病变的核心和边缘显著增加。详细的空间分析显示，激活的小胶质细胞/巨噬细胞周围未受损的轴突束不表达ED 1，吞噬细胞的标志物，而受损束内的表达ED 1。这些结果提示中性粒细胞和小胶质细胞/巨噬细胞在缺血性卒中后白色物质损伤中的作用不同。活化的小胶质细胞/巨噬细胞的不同定位暗示了调节它们向受损白色物质的迁移和浸润的复杂信号。
After an ischemic stroke, there is a prolonged inflammatory response and secondary phase of injury that is more amenable to treatment than acute neurotoxicity. Surprisingly, little is known about temporal and spatial relationships between inflammation and white matter injury. Here, we quantified development of white matter damage, inflammation, and a glial limitans at 1, 3, and 7 days after transient ischemia in the rat striatum using immunohistochemistry. Quantitative analysis showed that decreased staining for myelin basic protein and increased staining for damaged myelin basic protein began in the core, coincided with neutrophil infiltration, and progressed outward over time. Axon damage (i.e. accumulation of amyloid precursor protein) began at the edge of the lesion, coinciding with substantial microglia/macrophage activation, and progressed into the core. During the 7 days, activated microglia/macrophages dramatically increased only in the core and edge of the lesion. Detailed spatial analyses revealed that activated microglia/macrophages that surrounded undamaged axon bundles did not express ED1, a marker of phagocytic cells, whereas those inside damaged bundles expressed ED1. These results imply different contributions of neutrophils and microglia/macrophages to white matter injury after ischemic stroke. The distinct localizations of activated microglia/macrophages imply complex signals that regulate their migration toward and infiltration of damaged white matter.