Dysregulation of RNF213 promotes cerebral hypoperfusion

• Morimoto, Takaaki

  Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine・Department of Neurosurgery, Kyoto University Graduate School of Medicine

• Enmi, Jun Ichiro

  Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita

• Hattori, Yorito

  Department of Neurology, National Cerebral and Cardiovascular Center, Suita

• Iguchi, Satoshi

  Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita

• Saito, Satoshi

  Department of Neurology, National Cerebral and Cardiovascular Center, Suita

• Harada, Kouji H.

  Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine

• Okuda, Hiroko

  Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine

• Mineharu, Yohei

  Department of Neurosurgery, Kyoto University Graduate School of Medicine

• Takagi, Yasushi

  Department of Neurosurgery, Kyoto University Graduate School of Medicine

• Youssefian, Shohab

  Laboratory of Molecular Biosciences, Kyoto University Graduate School of Medicine

• Iida, Hidehiro

  Department of Investigative Radiology, National Cerebral and Cardiovascular Center, Suita

• Miyamoto, Susumu

  Department of Neurosurgery, Kyoto University Graduate School of Medicine

• Ihara, Masafumi

  Department of Neurology, National Cerebral and Cardiovascular Center, Suita

• Kobayashi, Hatasu

  Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine・Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University

• Koizumi, Akio

  Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine

Abstract

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF.

Journal

• Scientific Reports

  Scientific Reports 8 3607-, 2018-02-26

  Nature Publishing Group

Keywords

• Multidisciplinary

Details

• CRID: 1050282813184357760
• NII Article ID: 120006510289
• NII Article ID: 120006535057
• ISSN: 20452322
• DOI: 10.1038/s41598-018-22064-8
• HANDLE: 2433/234203
• Web Site: http://repo.lib.tokushima-u.ac.jp/112440
• Web Site: https://www.nature.com/articles/s41598-018-22064-8
• Web Site: https://www.nature.com/articles/s41598-018-22064-8.pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN