title: High Serum MiR-130a Levels Are Associated with Severe Perihematomal Edema and Predict Adverse Outcome in Acute ICH.
abstract: 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.
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Meng-Die
authors: MD
authors: Wang
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Yong
authors: Y
authors: Wang
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Yuan-Peng
authors: YP
authors: Xia
authors: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Jing-Wen
authors: JW
authors: Dai
authors: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Lin
authors: L
authors: Gao
authors: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Si-Qi
authors: SQ
authors: Wang
authors: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Hai-Jun
authors: HJ
authors: Wang
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Ling
authors: L
authors: Mao
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Man
authors: M
authors: Li
authors: Department of Neurology, The Attached Hospital of Xinyang Vocational Technical College, Daqing Road, Xinyang, 464000, People's Republic of China.
authors: Shi-Meng
authors: SM
authors: Yu
authors: Department of Geratology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Donghu Road, Wuhan, 430077, People's Republic of China.
authors: Yan
authors: Y
authors: Tu
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Quan-Wei
authors: QW
authors: He
authors: Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430030, People's Republic of China.
authors: Guo-Peng
authors: GP
authors: Zhang
authors: Department of Neurosurgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Shengli Street, Wuhan, 430014, People's Republic of China.
authors: Lei
authors: L
authors: Wang
authors: Department of Neurosurgery, Wuhan General Hospital of Guangzhou Command, Wuluo Road, Wuhan, 430070, People's Republic of China.
authors: Guo-Zheng
authors: GZ
authors: Xu
authors: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China.
authors: Hai-Bo
authors: HB
authors: Xu
authors: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430030, People's Republic of China. zhulq1979@gmail.com.
authors: Ling-Qiang
authors: LQ
authors: Zhu
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022, People's Republic of China. hubo@mail.hust.edu.cn.|Key Laboratory of Neurological Disease, Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430030, People's Republic of China. hubo@mail.hust.edu.cn.
authors: Bo
authors: B
authors: Hu
mesh_terms: D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000097:blood* / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D051242:Caveolin 1 / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D003710:Demography; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006406:Hematoma / Q000097:blood / Q000150:complications / Q000235:genetics; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000097:blood*; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000494:pharmacology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051242:Caveolin 1; C554019:MIRN130 microRNA, human; C569198:MIRN130 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D013917:Thrombin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Biomarkers; Clinical outcome prediction; Intracerebral hemorrhage; MicroRNA-130a; Perihematomal edema
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