Elucidation of kidney-brain interaction in mouse models of renal ischemia/reperfusion injury and hypoxia

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K19470
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Keio University (2018); Tokyo Medical University (2015-2017)
• Principal Investigator: HIRANO-GONDO ASAKO (権藤麻子) 慶應義塾大学, 医学部(信濃町), 共同研究員 (70385079)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 脳腎連関

Outline of Final Research Achievements

We confirmed the model of the acute renal ischemia-reperfusion injury as an animal model to study kidney-brain interaction. Next, using the brain harvested at 24 h after surgery and processed for histologic examination, we evaluated the effect of renal ischemia reperfusion injury to the brain. We observed microglial cells in the cerebral cortex and hippocampus, but differences were noted among individuals. Although we also analyzed pyknotic neuronal cells, there was no definite tendency to the inflammatory change of kidney to the central nervous system in this model mouse which was shown in previous research. Aquaporin4, GFAP, β-dystroglycan, Claudin5 and HIF-1α expressions were examined in this model mouse, the molecular mechanism of kidney-brain interaction was unclear.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

近年、慢性腎臓病患者では脳卒中が増えることや、腎機能低下とともに無症候性脳梗塞が高頻度に認められることが報告され、脳腎連関の存在がクローズアップされている。しかし、虚血時に遠隔臓器である腎臓と脳の血管障害が互いにどのような影響を及ぼしているのか、分子細胞レベルでは解明されていない。本研究の遂行により、多臓器間のネットワーク分子メカニズム解明から、血管障害性腎疾患に伴う中枢神経障害に対する新たな治療開発や高齢化社会で問題となる認知症の治療開発へ繋がることが期待されると考えられたが、本研究において腎臓と大脳とのネットワーク分子は明らかではなかった。