Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9.
Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9.
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DOI：
10.1161/strokeaha.109.570515
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发表时间：
2010-03
期刊：
影响因子：
8.3
通讯作者：
Warach S
中科院分区：
文献类型：
--
作者：
Barr TL;Latour LL;Lee KY;Schaewe TJ;Luby M;Chang GS;El-Zammar Z;Alam S;Hallenbeck JM;Kidwell CS;Warach S
基质金属蛋白酶（MMP's）可能在缺血性卒中后血脑屏障（BBB）破坏中发挥作用。我们假设MMP-9的血浆浓度与急性卒中患者血脑屏障破坏的标志物相关。患者在就诊时和大约24小时后接受MRI。MRI标记物，称为高信号急性再灌注损伤标记物（HARM），是液体衰减反转恢复（FLAIR）MRI上脑脊液（CSF）的钆增强。ELISA法测定血浆MMP-9和基质金属蛋白酶组织抑制因子-1（TIMP-1）水平。Logistic回归模型分别对MMP-9和MMP-9/TIMP-1比值进行24小时随访扫描，以预测HARM。入组的41例患者的诊断为：急性缺血性脑血管综合征33例（80.6%），脑出血6例（14.6%），拟卒中1例（2.4%）和非卒中1例（2.4%）。17例（41.5%）患者存在伤害。在模型1中，HARM与基线血浆MMP-9浓度相关：比值比（OR）= 1.01（95%置信区间（CI）=1.001-1.019），p=0.033。在模型2中，HARM与MMP-9/TIMP-1比值相关：OR=4.94（95% CI=1.27-19.14），p=0.021。基线MMP-9是24小时随访时HARM的重要预测因子，支持MMP-9与BBB破坏相关的假设。如果MMP-9和BBB破坏之间的关联在未来的研究中得到证实，HARM可能是一个有用的成像标志物，以评估缺血性卒中和其他人群中的MMP-9抑制与BBB破坏。
Matrix metalloproteinases (MMP’s) may play a role in blood brain barrier (BBB) disruption following ischemic stroke. We hypothesized that plasma concentrations of MMP-9 are associated with a marker of BBB disruption in patients evaluated for acute stroke. Patients underwent MRI on presentation and approximately 24 hours later. The MRI marker, termed Hyperintense Acute reperfusion injuRy Marker (HARM), is gadolinium enhancement of cerebrospinal fluid (CSF) on fluid attenuated inversion recovery (FLAIR) MRI. Plasma MMP-9 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) was measured by ELISA. Logistic regression models tested for predictors of HARM on 24 hour follow-up scans separately for MMP-9 and the MMP-9/TIMP-1 ratio. For the 41 patients enrolled diagnoses were: acute ischemic cerebrovascular syndrome 33 (80.6%), intracerebral hemorrhage 6 (14.6%), stroke mimic 1 (2.4 %) and no stroke 1 (2.4%). HARM was present in 17 (41.5%) patients. In model 1, HARM was associated with baseline plasma MMP-9 concentration: odds ratio (OR) = 1.01 (95% confidence interval (CI) =1.001-1.019), p=0.033. In model 2, HARM was associated with the MMP-9/TIMP-1 ratio: OR=4.94 (95% CI=1.27-19.14), p=0.021. Baseline MMP-9 was a significant predictor of HARM at 24-hour follow-up, supporting the hypothesis that MMP-9 is associated with BBB disruption. If the association between MMP-9 and BBB disruption is confirmed in future studies, HARM may be a useful imaging marker to evaluate MMP-9 inhibition in ischemic stroke and other populations with BBB disruption.