Development of the new treatment of ischemic brain injury by regulating prostaglandin D2 synthesis

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591594
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Nagoya City University
• Principal Investigator: MASE Mitsuhito 名古屋市立大学, 大学院・医学研究科, 准教授 (60238920)
• Co-Investigator(Kenkyū-buntansha): ARITAKE Kosuke (財)大阪バイオサイエンス研究所, 分子行動生物学部門, 研究員 (70390804)
• Co-Investigator(Renkei-kenkyūsha): YAMADAKAZUO Kazuo 名古屋市立大学, 大学院・医学研究科, 教授 (90150341) ; URADE Yoshihiro (財)大阪バイオサイエンス研究所, 分子行動生物学部門, 研究部長 (10201360)
• Project Period (FY): 2010 – 2012
• Keywords: 脳梗塞 / プロスタグランジン D2 合成酵素阻害剤 / 霊長類モデル / 高次脳機能

Research Abstract

The purpose of this study is to clarify the efficacy of prostaglandin D2 synthase (PGDS) inhibitor on cerebral ischemia. We developed cerebral ischemia and reperfusion injury model using Cynomolgus monkeys. Ischemia was produced by a placement of a micro-catheter in the M1 portion of middle cerebral artery (MCA) for 3 hours, and reperfusion was made by withdrawal of the catheter. In this model, constant cerebral infarction in the MCA area was found. Usually, the animal died by cerebral herniation when infarct volume was more than 5000 mm3. In the treatment group, PGDS inhibitor (HQL79) was administer by oral one day before the ischemic insult. For one month monitoring, there was no side effect of this drug on the systemic condition and blood examinations of the animals. Brain edema after reperfusion (day 3) was tended to be reduced in the treatment group. One animal with 6689m3 of infarction volume survived. These results suggest that (PGDS) inhibitor may have a possibility to reduce ischemic brain injury. Further study will be needed to confirm this possibility.