医学
脑脊液
蛛网膜下腔出血
酶谱
基质金属蛋白酶
内科学
病理生理学
胶溶蛋白
病理
胃肠病学
生物化学
生物
肌动蛋白
作者
Martin N. Stienen,Po-Shun Lee,Rachael G. Konigsberg,Dana Gallacci,Terry Ting-Yu Chiou,Ken Arai,Suzanne Simmons,David Bauer,Steven K. Feske,Eng H. Lo,MingMing Ning
出处
期刊:Stroke
[Ovid Technologies (Wolters Kluwer)]
日期:2011-12-01
卷期号:42 (12): 3624-3627
被引量:36
标识
DOI:10.1161/strokeaha.111.631135
摘要
Subarachnoid hemorrhage (SAH) pathophysiology involves neurovascular proteolysis and inflammation. How these 2 phenomena are related remains unclear. We hypothesize that matrix metalloproteinases (MMPs) mediate the depletion of anti-inflammatory plasma-type gelsolin (pGSN).We enrolled 42 consecutive SAH subjects and sampled cerebrospinal fluid (CSF) and blood on post-SAH Days 2 to 3, 4 to 5, 6 to 7, and 10 to 14. Control subjects were 20 consecutive non-SAH hydrocephalus patients with lumbar drains. Enzyme-linked immunosorbent assay, Western blotting, and zymography were used to quantify pGSN and MMP-9.In CSF, pGSN was lower in SAH compared with control subjects on post-SAH Days 2 to 3 (P=0.0007), 4 to 5 (P=0.041), and 10 to 14 (P=0.007). In blood, pGSN decreased over time (P=0.001) and was lower in SAH compared with control subjects on post-SAH Days 4 to 5 (P=0.037), 6 to 7 (P=0.006), and 10 to 14 (P=0.006). Western blots demonstrated that SAH CSF had novel bands at 52 and 46 kDa, representing cleaved pGSN fragments. Gelatin zymography showed that CSF MMP-9 was elevated in SAH compared with control subjects. Higher CSF MMP-9 correlated with lower CSF pGSN on post-SAH Day 7 (r=-0.38; P=0.05).SAH is associated with decreased CSF and blood pGSN and elevated CSF MMP-9. Novel cleaved pGSN fragments are present in CSF of SAH subjects, consistent with pGSN cleavage by MMPs. Because pGSN is known to inhibit inflammatory mediators, these findings suggest that MMPs may reduce pGSN and exacerbate inflammation after SAH. Further studies are warranted to investigate the mechanisms underlying MMP-pGSN signaling in SAH.
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