title: Sodium Tanshinone IIA Sulfonate Enhances Effectiveness Rt-PA Treatment in Acute Ischemic Stroke Patients Associated with Ameliorating Blood-Brain Barrier Damage.
abstract: Treatment with sodium tanshinone IIA sulfonate (STS) may ameliorate blood-brain barrier (BBB) damage in acute ischemic stroke patients receiving recombinant tissue plasminogen activator (rt-PA) thrombolysis and improve stroke patients' outcome. This randomized, single-center, placebo-controlled clinical trial investigated the potential effects and underlying mechanisms of STS. Forty-two acute ischemic stroke patients receiving intravenous rt-PA thrombolysis were randomized to intravenous administration either with STS (60 mg/day) (n = 21) or with equivalent volume of saline as a placebo (n = 21) after randomization for 10 days. Clinical outcomes, computer tomography perfusion (CTP) imaging with permeability-surface area product (PS) maps and serum levels of BBB damage biomarkers, were compared between the two groups. The percentage of patients with excellent functional outcome indicated by a 90-day mRS ≤1 was significantly higher in the STS group than in the placebo group (p = 0.028). For patients with CTP imaging (n = 30), PS in the ipsilateral lesion (p = 0.034) and relative PS (p = 0.013) were significantly lower in the STS group than that in placebo. STS-treated patients also had lower levels of matrix metalloproteinase (MMP)-9 (p = 0.036) and claudin-5 (p = 0.026), but higher levels of tissue inhibitor of metalloproteinase (TIMP)-1 (p = 0.040) than those in the placebo group. Post-stroke STS treatment could improve neurologic functional outcomes for acute ischemic stroke patients following rt-PA treatment by reducing BBB leakage and damage, which might be mechanistically associated with MMP-9 inhibition.
authors.affiliation: Department of Neurology and Radiology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Biying
authors.initials: B
authors.lastname: Ji
authors.affiliation: Department of Neurology and Radiology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Neurology and Radiology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Han
authors.affiliation: GE Healthcare, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurology and Radiology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Neurology and Radiology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurology and Radiology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology and Radiology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Departments of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Departments of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology and Radiology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory for Molecular Medicine of Nanjing University, Nanjing, People's Republic of China. xuyun20042001@aliyun.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications; D062507:Claudin-5 / Q000097:blood; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010616:Phenanthrenes / Q000627:therapeutic use*; D011446:Prospective Studies; D020521:Stroke / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D062826:Zonula Occludens-1 Protein / Q000097:blood
chemical_list: C107466:CLDN5 protein, human; D062507:Claudin-5; D005343:Fibrinolytic Agents; D010616:Phenanthrenes; D019715:Tissue Inhibitor of Metalloproteinase-1; D062826:Zonula Occludens-1 Protein; C024894:tanshinone II A sodium sulfonate; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1
keywords: Blood-brain barrier; CT perfusion; Permeability surface; Sodium tanshinone IIA sulfonate; Thrombolysis