TY - JOUR
T1 - SMTP-7, a new thrombolytic agent, decreases hemorrhagic transformation after transient middle cerebral artery occlusion under warfarin anticoagulation in mice
AU - Ito, Akira
AU - Niizuma, Kuniyasu
AU - Shimizu, Hiroaki
AU - Fujimura, Miki
AU - Hasumi, Keiji
AU - Tominaga, Teiji
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid from the Japan Brain Foundation (KN) and a Grant from the Japan Science and Technology Corporation Agency (TT, KH).
Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
PY - 2014
Y1 - 2014
N2 - Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a new thrombolytic agent that exhibits anti-inflammatory effects. We previously demonstrated that the hemorrhagic transformation was fewer with SMTP-7 than with recombinant tissue plasminogen activator (rt-PA) following ischemia-reperfusion in animal models. We hypothesized that SMTP-7 may decrease hemorrhagic transformation after ischemia-reperfusion under the warfarin-treated condition. Transient middle cerebral artery occlusion (MCAO) was induced for 3 h using an intraluminal suture in warfarin-treated mice to produce hemorrhagic transformation. Warfarin was administered orally for a 24-h feeding period before MCAO through bottled drinking water (5 mg in 375 ml tap water), resulting in a mean INR of 5.6×0.2. Mice were treated with vehicle, rt-PA, or SMTP-7 5h before reperfusion. Twenty percent of vehicle-treated and 50.0% of rt-PA-treated mice died 24 h after reperfusion, while all SMTP-7-treated mice survived. Hemorrhagic severity in SMTP-7-treated mice was significantly lower than that in rt-PA-treated mice. Neurological deficit was significantly lower in SMTP-7-treated mice than vehicle- and rt-PA-treated mice. These results indicate that SMTP-7 decreases mortality, hemorrhagic transformation, and neurological deficits, and can be a safe thrombolytic agent following MCAO under the warfarin-treated condition.
AB - Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a new thrombolytic agent that exhibits anti-inflammatory effects. We previously demonstrated that the hemorrhagic transformation was fewer with SMTP-7 than with recombinant tissue plasminogen activator (rt-PA) following ischemia-reperfusion in animal models. We hypothesized that SMTP-7 may decrease hemorrhagic transformation after ischemia-reperfusion under the warfarin-treated condition. Transient middle cerebral artery occlusion (MCAO) was induced for 3 h using an intraluminal suture in warfarin-treated mice to produce hemorrhagic transformation. Warfarin was administered orally for a 24-h feeding period before MCAO through bottled drinking water (5 mg in 375 ml tap water), resulting in a mean INR of 5.6×0.2. Mice were treated with vehicle, rt-PA, or SMTP-7 5h before reperfusion. Twenty percent of vehicle-treated and 50.0% of rt-PA-treated mice died 24 h after reperfusion, while all SMTP-7-treated mice survived. Hemorrhagic severity in SMTP-7-treated mice was significantly lower than that in rt-PA-treated mice. Neurological deficit was significantly lower in SMTP-7-treated mice than vehicle- and rt-PA-treated mice. These results indicate that SMTP-7 decreases mortality, hemorrhagic transformation, and neurological deficits, and can be a safe thrombolytic agent following MCAO under the warfarin-treated condition.
KW - Cerebral infarction
KW - Focal ischemia
KW - Hemorrhagic transformation
KW - Recombinant tissue plasminogen activator
KW - Thrombolysis
KW - Warfarin
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U2 - 10.1016/j.brainres.2014.07.004
DO - 10.1016/j.brainres.2014.07.004
M3 - Article
C2 - 25016287
AN - SCOPUS:84926137671
VL - 1578
SP - 38
EP - 48
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
ER -