K-134, a phosphodiesterase 3 inhibitor, prevents brain damage by inhibiting thrombus formation in a rat cerebral infarction model

• Published in: PloS one 2012-10, Vol.7 (10), p.e46432-e46432
• Main Authors: Yoshida, Hideo, Ashikawa, Yuka, Itoh, Shinsuke, Nakagawa, Takashi, Asanuma, Akimune, Tanabe, Sohei, Inoue, Yoshihiro, Hidaka, Hiroyoshi
• Format: Article
• Language: English
• Subjects: Animals; Antiplatelet therapy; Blood clots; Blood platelets; Brain; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain damage; Brain injury; Brain research; Cerebral blood flow; Cerebral infarction; Cerebral Infarction - drug therapy; Cerebral Infarction - pathology; Cerebral ischemia; Complications and side effects; Damage prevention; Disease; Disease prevention; Dosage and administration; Drug therapy; Experiments; Hypertension; Infarction; Ischemia; Laboratories; Male; Medicine; Mice; Mice, Inbred ICR; Occlusion; Phosphodiesterase; Phosphodiesterase 3 Inhibitors - therapeutic use; Platelet aggregation; Platelet aggregation inhibitors; Prevention; Quinolines - therapeutic use; Rats; Rats, Sprague-Dawley; Risk factors; Rodents; Stroke; Systematic review; Thromboembolism; Thrombosis; Thrombosis - prevention & control; Traumatic brain injury; Urea - analogs & derivatives; Urea - therapeutic use
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046432

K-134 is a more potent antiplatelet drug with a selective inhibitory effect on phosphodiesterase 3 (PDE3) compared with its analogue, cilostazol. This study was performed to compare the ameliorating effects of K-134 and cilostazol on brain damage in an experimental photothrombotic cerebral infarction model. We investigated the effects of oral preadministration of PDE3 inhibitors in a rat stroke model established by photothrombotic middle cerebral artery (MCA) occlusion. K-134 significantly prolonged MCA occlusion time at doses >10 mg/kg, and reduced cerebral infarct size at 30 mg/kg in the stroke model (n = 12, 87.5±5.6 vs. 126.8±7.5 mm(3), P