NDLI: Distinct effects of tissue-type plasminogen activator and SMTP-7 on cerebrovascular inflammation following thrombolytic reperfusion.

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Distinct effects of tissue-type plasminogen activator and SMTP-7 on cerebrovascular inflammation following thrombolytic reperfusion.

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Distinct effects of tissue-type plasminogen activator and SMTP-7 on cerebrovascular inflammation following thrombolytic reperfusion.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hasumi, Keiji Miyazaki, Takuro Hashimoto, Terumasa Shibata, Keita Ohata, Hisayuki Kimura, Yuji Honda, Kazuo
Description	Author Affiliation: Miyazaki T ( Department of Pharmacology, School of Pharmacy, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8555 Japan. taku@pharm.showa-u.ac.jp)
Abstract	BACKGROUND AND PURPOSE: Thrombolysis therapy using tissue-type plasminogen activator (t-PA) is occasionally accompanied by harmful outcomes, including intracerebral hemorrhage. We have reported that Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a candidate thrombolytic drug, has excellent therapeutic effect on cerebral infarction in embolic stroke model in mice; however, little is known regarding whether this agent influences cerebrovascular inflammation following thrombolytic reperfusion. The current study aimed to compare the effects of recombinant t-PA (rt-PA) and SMTP-7 on cerebrovascular inflammation. METHODS: The impact of rt-PA- and SMTP-7-induced thrombolytic reperfusion on leukocyte dynamics was investigated in a photochemically induced thrombotic middle cerebral artery occlusion (tMCAo) model in mice. RESULTS: Both rt-PA and SMTP-7 administration in tMCAo mice (each 10 mg/kg) resulted in thrombolytic reperfusion. The SMTP-7-administered mice showed relatively mild rolling and attachment of leukocytes to the vascular wall in the middle cerebral vein, with weak peroxynitrite reactions and proinflammatory gene expression (IL-1ß, TNF- , ICAM-1, and VCAM-1); thus, a small infarct volume compared with rt-PA-administered mice. In vitro study suggested that rt-PA at 20 µg/mL, but not SMTP-7 at a similar concentration, promotes cytokine-induced reactive oxygen species generation in cultured endothelial cells; moreover, SMTP-7 suppressed cytokine-induced VCAM-1 induction in the cells and leukocyte/ endothelial cell adhesions. CONCLUSIONS: Relatively mild cerebrovascular inflammation and cerebral infarction in the SMTP-7 mice, compared with in rt-PA mice, is thought to be caused at least in part by direct antioxidative actions of SMTP-7 in ECs.
ISSN	00392499
e-ISSN	15244628
Journal	Stroke
Issue Number	4
Volume Number	42
Language	English
Publisher	Lippincott Williams & Wilkins (on behalf of the American Heart Association)
Publisher Date	2011-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Benzopyrans Toxicity Infarction, Middle Cerebral Artery Pathology Intracranial Embolism Pyrrolidinones Reperfusion Injury Thrombolytic Therapy Tissue Plasminogen Activator Animals Antagonists & Inhibitors Cell Line, Tumor Cells, Cultured Disease Models, Animal Drug Therapy Etiology Inflammation Enzymology Lasers Mice Comparative Study Research Support, Non-u.s. Gov't Discipline Cardiology
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Advanced and Specialized Nursing Neurology (clinical)

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