Establishment of novel prophylaxis/treatment for cerebral infarction using SIRT1 activator

2015 Fiscal Year Final Research Report

• Project/Area Number: 26640034
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Hattori Yorito 国立研究開発法人国立循環器病研究センター, 病院, 客員研究員 (60713849)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: SIRT1 / 頸動脈狭窄症 / 血管性認知症 / 脳血流量

Outline of Final Research Achievements

We hypothesized that SIRT1 counertacts cerebral ischemia/hypoperfusion.
We did the bilateral common carotid artery stenosis (BCAS) surgery to Sirt1 transgenic (Sirt1-Tg) mice and wild-type (WT) littermates, which induces chronic cerebral hypoperfusion. WT mice showed working memory impairment and cerebral white matter ischemic injury, but Sirt1-Tg mice preserved memory function and cerebral histologic integrity at 1 month after BCAS. For Sirt1-Tg mice showed continuously preserved cerebral blood flow after BCAS even though CBF of WT mice decreased to 70-80% of baseline after the surgery. The mechanism is that SIRT1 deacetylate endothelial nitric oxide synthase (eNOS) and activated that so that cerebral arteries dilate.
We are going to try the clinical research using SIRT1 activator.

Free Research Field

神経内科学