Tissue plasminogen activator (t-PA) has a short therapeutic time window for administration (3 h) and carries a risk of promoting
intracerebral hemorrhage. The aim of the present study was to investigate a therapeutic time window and frequency of hemorrhagic region by treatment with Stachybotrys microspora triprenyl phenol-7 (SMTP-7). Thrombotic occlusion was induced by transfer of
acetic acid-induced
thrombus at the right common carotid artery into the brain of mice.
Infarction area, neurological score,
edema percentage, and regional cerebral blood flow (CBF) were determined as the index of the efficacy of
SMTP-7. In order to evaluate the mechanism of
SMTP-7,
plasmin activities and the expressions of
interleukin (IL)-1beta,
tumor necrosis factor-alpha (
TNF-alpha), and
IL-6 mRNA were examined.
SMTP-7 (0.1, 1, 10 mg/kg) dose dependently reduced
infarction area, neurological score, and
edema percentage. Additionally, its therapeutic time window was longer than that of t-PA, a high-molecular-weight compound. In addition, little hemorrhagic region was induced by treatment with
SMTP-7.
SMTP-7 showed
plasmin activity in vivo and caused a decreased CBF to recover. Furthermore, the expressions of inflammatory
cytokine mRNA (IL-1beta, TNF-alpha, IL-6) were increased by t-PA treatment 3 h after
ischemia but were not induced by
SMTP-7 treatment. These results indicate that
SMTP-7 shows potential thrombolytic and anti-inflammatory effects as well as a wide therapeutic time window and little hemorrhagic region compared with that of t-PA. Therefore, this novel low-molecular-weight compound may represent a novel approach for the treatment of
cerebral infarction.