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High Serum MiR-130a Levels Are Associated with Severe Perihematomal Edema and Predict Adverse Outcome in Acute ICH

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单位: [1]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Neurol, Jiefang Ave, Wuhan 430022, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathophysiol, Jiefang Ave, Wuhan 430030, Peoples R China [3]Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Jiefang Ave, Wuhan 430030, Peoples R China [4]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Radiol, Jiefang Ave, Wuhan 430022, Peoples R China [5]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Neurosurg, Jiefang Ave, Wuhan 430022, Peoples R China [6]Wuhan Gen Hosp Guangzhou Command, Dept Neurosurg, Wuluo Rd, Wuhan 430070, Peoples R China [7]Huazhong Univ Sci & Technol, Cent Hosp ofWuhan, Tongji Med Coll, Dept Neurosurg, Shengli St, Wuhan 430014, Peoples R China [8]Attached Hosp Xinyang Vocat Tech Coll, Dept Neurol, Daqing Rd, Xinyang 464000, Peoples R China [9]Huazhong Univ Sci & Technol, Liyuan Hosp, TongjiMed Coll, Dept Geratol, Donghu Rd, Wuhan 430077, Peoples R China [10]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Nucl Med, Jiefang Ave, Wuhan 430030, Peoples R China
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关键词: Intracerebral hemorrhage Perihematomal edema Clinical outcome prediction Biomarkers MicroRNA-130a

摘要:
The development and/or progression of perihematomal edema (PHE) in patients with acute spontaneous intracerebral hemorrhage (ICH) vary substantially with different individuals. Although hematoma volume is a useful indicator for predicting PHE, its predictive power was not good at the early stage of ICH. Better predictors are urgently needed. In this study, we found that miR-130a was elevated in the serum of ICH patients and was an independent indicator positively associated with PHE volume within the first 3 days after onset. The R (2) was further evaluated when it is used in combination with hematoma mass. Serum miR-130a levels were associated with clinical outcome (National Institute of Health Stroke Scale (NIHSS) scores at day 14 and modified Rankin Scale (mRS) scores at day 90) only in patients with deep hematoma. Moreover, miR-130a was significantly increased in rat serum and perihematomal tissues and was in line with the change in brain edema. MiR-130a inhibitors reduced brain edema, blood-brain barrier (BBB) permeability, and increased neurological deficit scores, and miR-130a mimics increased monolayer permeability. Thrombin-stimulated brain microvascular endothelial cells (BMECs) were a main source of miR-130a under ICH. In the experimental model, the elevated miR-130a level was accompanied by the decreased caveolin-1 and increased matrix metalloproleinase (MMP)-2/9. Meanwhile, caveolin-1 (cav-1) was reduced by miR-130a mimics, accompanied by an increase in MMP-2/9 expression. The upregulated MMP-2/9 was then downregulated by cavtratin, a cav-1 scaffolding domain peptide. This regulation mechanism was authenticated in a thrombin-induced cellular ICH model. Our results suggest that serum miR-130a may serve as a useful early biomarker for monitoring post-ICH PHE and predicting prognosis and may be helpful in the decision-making of individualized therapy.

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出版当年[2015]版:
大类 | 2 区 医学
小类 | 2 区 神经科学
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大类 | 2 区 医学
小类 | 2 区 神经科学
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Q1 NEUROSCIENCES
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Q1 NEUROSCIENCES

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第一作者单位: [1]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Neurol, Jiefang Ave, Wuhan 430022, Peoples R China
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通讯机构: [1]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Neurol, Jiefang Ave, Wuhan 430022, Peoples R China [3]Huazhong Univ Sci & Technol, Tongji Med Coll, Key Lab Neurol Dis, Minist Educ, Jiefang Ave, Wuhan 430030, Peoples R China
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