The beneficial role of renal denervation in the prognosis of subarachnoid hemorrhage

• Project/Area Number: 15K10309
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kumamoto University
• Principal Investigator: Hasegawa Yu 熊本大学, 大学院生命科学研究部(医), 講師 (40599114)
• Co-Investigator(Kenkyū-buntansha): 鯉渕 信孝 熊本大学, 大学院生命科学研究部(医), 助教 (30456131) ; 河野 隆幸 熊本大学, 医学部附属病院, 講師 (50448536)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: くも膜下出血 / 脳血管攣縮 / 腎除神経術 / 視床下部室傍核 / 早期脳損傷 / 視床下部 / クモ膜下出血 / ラット

Outline of Final Research Achievements

The aim of the project was to explore the protective effect of renal denervation (RD) on the prognosis of experimental subarachnoid hemorrhage (SAH). The rats were performed bilateral RD after SAH induction. RD prevented cerebral vasospasm which were one of the main determinant factors for SAH prognosis and ameliorated SAH-induced cytotoxic changes in endothelial cells of cerebral arteries. RD reduced cellular injuries and sympathetic nerve activation in hypothalamic periventricular nucleus. RD also decreased upregulated serum angiotensin II by SAH. Those findings indicated that RD prevented cerebral vasospasm through reduction of endothelial cell damage by SAH and the effects might be associated with inhibition of hypothalamic injuries, and deactivation of sympathetic nerve activity and subsequent increased renin-angiotensin system.

Academic Significance and Societal Importance of the Research Achievements

長年議論の的だった交感神経とくも膜下出血(SAH)後脳血管攣縮との関連性について、本研究では中枢性交感神経系を担う視床下部に焦点を当てて、それらの正の関連性を明らかにした。腎除神経術(RD)は、視床下部傷害を軽減し交感神経過活動を抑制した結果、強い血管収縮作用を持ち交感神経活動を修飾し得るアンギオテンシンIIを不活化することで血管内皮細胞保護を発揮し、SAH後脳血管攣縮を軽減したと考えられた。RDは治療抵抗性高血圧患者の新たな治療法となるべく、現在臨床研究が行われている。従って本研究結果は、RDがヒトSAH後脳血管攣縮の治療法に将来応用できる可能性を示唆するものとなった。

Research Products

• [Journal Article] Exploring the pathogenesis of subarachnoid haemorrhages (SAH) using an animal model (2019)
  • Author(s): Hasegawa Yu
  • Journal Title: Impact Volume: 2019 Issue: 4 Pages: 51-53
  • DOI: 10.21820/23987073.2019.4.51
  • Open Access
• [Journal Article] スパズム発症に関与するレニンアンギオテンシン系の活性化 (2018)
  • Author(s): 長谷川雄、岳元裕臣、林建佑、光山勝慶
  • Journal Title: 脳血管攣縮 Volume: 34 Pages: 1-5
  • Peer Reviewed
• [Journal Article] 交感神経活動抑制をターゲットとしたスパズム治療の展望 (2017)
  • Author(s): 長谷川雄、岳元裕臣、林建佑、光山勝慶
  • Journal Title: 脳血管攣縮 Volume: 33 Pages: 9-13
  • Peer Reviewed
• [Presentation] Renal Denervation Reduces Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats (2019)
  • Author(s): Yushin Takemoto, Yu Hasegawa, Kenyu Hayashi, Shokei Kim-Mitsuyama
  • Organizer: International Stroke Conference
  • Int'l Joint Research
• [Presentation] 腎除神経術はラットくも膜下出血後の中枢性交感神経活性化を抑制し脳血管攣縮を軽減する (2019)
  • Author(s): 岳元裕臣、長谷川雄、林建佑、光山勝慶
  • Organizer: Stroke 2019
• [Presentation] スパズム発症に関与するレニンアンギオテンシン系の活性化 (2018)
  • Author(s): 長谷川雄
  • Organizer: Stroke 2018
• [Presentation] 中枢性交感神経活動制御を目的としたスパズム治療の展望 (2017)
  • Author(s): 長谷川 雄
  • Organizer: Stroke 2017
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2017-03-16