Elucidation of the mechanism of cerebral infarction using genome-edited rats

• Project/Area Number: 18K14917
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Shinshu University
• Principal Investigator: Akemi Kakino 信州大学, 学術研究院医学系, 助教 (00534637)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 脳梗塞 / LOX-1

Outline of Final Research Achievements

In this study, we investigated the functional role of LOX-1 in stroke development and progression using LOX-1 knockout Stroke-Prone Spontaneously Hypertensive Rat (SHRSP) produced by genome editing technology. The results of pathology analysis by clinical symptoms and MRI imaging of the rat showed that cerebral infarction was found to be delayed by LOX-1 deficiency. In addition, gene expression analysis and microRNA expression analysis before and after stroke showed that the neuroprotective effect was increased in LOX-1-deficient rats. Our data indicate that LOX-1 is involved in stroke development and progression, and it is suggested that inhibition of LOX-1 action may be a target for new preventive / therapeutic methods for stroke.

Academic Significance and Societal Importance of the Research Achievements

脳梗塞は要介護状態を招く最も予防が重要な疾患である。本研究成果では、病理学的にヒトの脳卒中とよく類似しているSHRSPでLOX-1を欠損させると脳梗塞の発症や病態進行が遅延することを示した。すなわち、LOX-1作用阻害が、脳梗塞の新しい予防・治療法のための標的となる可能性を見出した。