Sodium Tanshinone IIA Sulfonate Enhances Effectiveness Rt-PA Treatment in Acute Ischemic Stroke Patients Associated with Ameliorating Blood-Brain Barrier Damage

• Published in: Translational stroke research 2017-08, Vol.8 (4), p.334-340
• Main Authors: Ji, Biying, Zhou, Fei, Han, Lijuan, Yang, Jun, Fan, Haijian, Li, Shanshan, Li, Jingwei, Zhang, Xin, Wang, Xiaoying, Chen, Xiangyan, Xu, Yun
• Format: Article
• Language: English
• Subjects: Activities of daily living; Adolescent; Adult; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Blood pressure; Blood-brain barrier; Blood-Brain Barrier - diagnostic imaging; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - pathology; Brain Ischemia - complications; Cardiology; Cardiovascular disease; Claudin-5 - blood; Clinical outcomes; Contrast agents; Double-Blind Method; Drug Synergism; Female; Fibrinolytic Agents - therapeutic use; Humans; Ischemia; Male; Matrix Metalloproteinase 1 - blood; Matrix Metalloproteinase 9 - blood; Middle Aged; Neurology; Neurosciences; Neurosurgery; Original; Original Article; Patients; Permeability; Phenanthrenes - therapeutic use; Prospective Studies; Stroke; Stroke - blood; Stroke - diagnostic imaging; Stroke - drug therapy; Stroke - etiology; Tissue Inhibitor of Metalloproteinase-1 - blood; Tissue Plasminogen Activator - therapeutic use; Treatment Outcome; Vascular Surgery; Young Adult; Zonula Occludens-1 Protein - blood
• ISSN: 1868-4483; 1868-601X
• DOI: 10.1007/s12975-017-0526-6

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.