A Novel Embolic Model of Cerebral Infarction and Evaluation of Stachybotrys microspora Triprenyl Phenol-7 (SMTP-7), a Novel Fungal Triprenyl Phenol Metabolite

• Published in: Journal of Pharmacological Sciences 2010, Vol.114(1), pp.41-49
• Main Authors: Hashimoto, Terumasa, Shibata, Keita, Nobe, Koji, Hasumi, Keiji, Honda, Kazuo
• Format: Article
• Language: English
• Subjects: acetic acid; Animals; Benzopyrans - isolation & purification; Benzopyrans - metabolism; Benzopyrans - therapeutic use; cerebral infarction; Cerebral Infarction - diagnosis; Cerebral Infarction - drug therapy; Cerebral Infarction - physiopathology; Disease Models, Animal; Drug Evaluation, Preclinical - methods; embolus; Gerbillinae; Intracranial Embolism - drug therapy; Intracranial Embolism - pathology; Intracranial Embolism - physiopathology; Male; Pyrrolidinones - isolation & purification; Pyrrolidinones - metabolism; Pyrrolidinones - therapeutic use; Stachybotrys; Stachybotrys microspora triprenyl phenol-7 (SMTP-7)
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.10131FP

The aim of the present study was to establish a novel embolic model of cerebral infarction and to evaluate the effect of Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a novel fungal triprenyl phenol metabolite. Thrombotic occlusion was induced by transfer of acetic acid–induced embolus into the brain. The regional cerebral blood flow was measured by a laser Doppler flowmeter to check the ischemic condition. Infarction area was assessed by 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological scores were determined by a modified version of the method described by Longa et al. Emboli were accumulated at the temporal or parietal region of the middle cerebral artery. Additionally, we found that this model showed decreased cerebral blood flow and increased infarction area and neurological scores. Treatment with tissue plasminogen activator (t-PA) reduced infarction area and the neurological scores in a dose-dependent manner; moreover, the decreased cerebral blood flow recovered. SMTP-7 also reduced these values. The therapeutic time window of SMTP-7 was longer than that of t-PA. These results indicate that this model may be useful for understanding the pathophysiological mechanisms of cerebral infarction and evaluating the effects of therapeutic agents. Additionally, SMTP-7 is a promising approach to extend the therapeutic time window. Therefore, this novel compound may represent a novel approach for the treatment of cerebral infarction.