Water-free Na accumulation facilitates the formation of cerebral aneurysm through down-regulation of sodium excretion pump in ovariectomized rats

• Project/Area Number: 24592131
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: The University of Tokushima
• Principal Investigator: SATOMI Junichiro 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (10304510)
• Co-Investigator(Kenkyū-buntansha): NAGAHIRO Shinji 徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授 (60145315) ; TADA Yoshiteru 徳島大学, 大学院ヘルスバイオサイエンス研究部, 助教 (30547964) ; KANEMATSU Yasuhisa 徳島大学, 病院, 助教 (90363142)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脳・神経 / 脳血管病 / エストロゲン / 高塩分摂取 / 高血圧 / 体内塩分貯留 / 脳動脈瘤破裂 / ミネラルコルチコイド受容体 / 脳神経疾患 / 脳動脈瘤 / ミネラルコルチコイド

Outline of Final Research Achievements

Hypertension is thought to be associated with a high incidence of stroke. However, not all patients with unruptured cerebral aneurysms are hypertensive. We hypothesized that in oophorectomized rats fed a high salt diet (HSD), body water-free Na+ accumulation may be increased, leading to the formation of cerebral aneurysms. Compared to HSD rats, the incidence of cerebral aneurysms and the body Na+-to-water ratio were significantly higher in HSD/OVX- and HSD/OVX/renal hypertensive (RL) rats independent of hypertension. In their aneurysmal wall, ATP1α2, a subtype of Na+/K+-ATPase were down-regulated and renin-angiotensin system- and inflammation related molecules were up-regulated. A reduction in the vascular Na efflux pump in ovariectomized rats may be associated with the increase in water-free Na+ accumulation directing to cerebral aneurysm formation.

Research Products

• [Journal Article] Prevention of Retrograde Blood Flow Into Large or Giant Internal Carotid Artery Aneurysms by Endovascular Coil Embolization with High-Flow Bypass: Surgical Technique and Long-Term Results (2015)
  • Author(s): Nakajima N, Nagahiro S, Satomi J, Tada Y, Nakajima K, Sogabe S, Hanaoka M, Matsubara S, Uno M, Satoh K
  • Journal Title: World Neurosurg Volume: in press
  • Peer Reviewed
• [Journal Article] Two-layered susceptibility vessel sign on 3-tesla T2*-weighted imaging is a predictive biomarker of stroke subtype (2015)
  • Author(s): Yamamoto N, Satomi J, Tada Y, Harada M, Izumi Y, Nagahiro S, Kaji R
  • Journal Title: Stroke Volume: 46 Pages: 269-271
  • Peer Reviewed
• [Journal Article] Brush sign on 3-T T2*-weighted MRI as a potential predictor of hemorrhagic transformation after tissue plasminogen activator therapy (2014)
  • Author(s): Terasawa Y, Yamamoto N, Morigaki R, Fujita K, Izumi Y, Satomi J, Harada M, Nagahiro S, Kaji R
  • Journal Title: Stroke Volume: 45 Pages: 274-276
  • Peer Reviewed
• [Journal Article] Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator? (2014)
  • Author(s): Yamamoto N, Satomi J, Harada M, Izumi Y, Nagahiro S, Kaji R
  • Journal Title: Clin Neuroradiol Volume: Equib
  • Peer Reviewed
• [Journal Article] Intra-arterial signal on arterial spin labeling perfusion MRI to identify the presence of acute middle cerebral artery occlusion (2014)
  • Author(s): Tada Y, Satomi J, Abe T, Kuwayama K, Sogabe S, Fujita K, Yamamoto N, Kaji R, Harada M, Nagahiro S
  • Journal Title: Cerebrovasc Dis Volume: 38 Pages: 191-196
  • Peer Reviewed
• [Journal Article] Acquired Pial and Dural Arteriovenous Fistulae following Superior Sagittal Sinus Thrombosis in Patients with Protein S Deficiency: A Report of Two Cases (2014)
  • Author(s): Matsubara S, Satoh K, Satomi J, Shigekiyo T, Kinouchi T, Miyake H, Nagahiro S
  • Journal Title: Neurol Med Chir (Tokyo) Volume: 54 Pages: 245-252
  • NAID: 130003383231
  • Peer Reviewed
• [Journal Article] Frequency of emerging positive diffusion-weighted imaging in early repeat examinations at least 24 h after transient ischemic attacks (2013)
  • Author(s): Morita N, Harada M, Satomi J, Terasawa Y, Kaji R, Nagahiro S
  • Journal Title: Neuroradiology/s00234-012-1113-x Volume: 55 Pages: 399-403
  • Peer Reviewed
• [Journal Article] Increase in body Na+-to-water ratio is associated with cerebral aneurysm formation in oophorectomized rats (2012)
  • Author(s): Matsushita N, et al.
  • Journal Title: Hypertension Volume: 60 Pages: 1309-1315
  • Peer Reviewed
• [Presentation] Role of hyperhomocysteinemia in the development of intracranial aneurysms (2015)
  • Author(s): Korai M, Kitazato KT, Miyamoto T, Shimada K, Yagi K, Tada Y, Kurashiki Y, Kuwayama K, Satomi J, Nagahiro S
  • Organizer: International Stroke Conference
  • Place of Presentation: Nashville、USA
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Hemodynamic change elicits the formation and rupture of experimental cerebral aneurysms (2015)
  • Author(s): Miyamoto T, David K. Kung, Korai M, Kitazato KT, Shimada K, Yagi K, Tada Y, Kurashiki Y, Kuwayama K, Satomi J, Nagahiro S
  • Organizer: International Stroke Conference
  • Place of Presentation: Nashville、USA
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Is the regulation of M1 macrophage activation beneficial in the acute phase of post cerebral ischemia? (2015)
  • Author(s): Kurashiki Y, Kitazato K, Uto Y, Yagi K, Shimada K, Miyamoto T, Sumiyoshi M, Tada Y, Kuwayama K, Satomi J, Nagahiro S
  • Organizer: International Stroke Conference
  • Place of Presentation: Nashville、USA
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Activation of M2 macrophage in the late phase after cerebral ischemia promotes the expression of neurogenesis related molecules (2014)
  • Author(s): Kurashiki Y, Kitazato K1, Uto Y, Yagi K, Shimada K, Miyamoto T1, Sumiyoshi M, Tada Y, Kuwayama K, Satomi J, Nagahiro S
  • Organizer: 9th World Stroke Congress
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2014-10-22 – 2014-10-25
• [Presentation] Hemodynamic changes may elicit the formation and rupture of experimental cerebral aneurysms (2014)
  • Author(s): Miyamoto T, David K. Kung, Korai M, Kitazato KT, Shimada K, Yagi K, Tada Y, Kurashiki Y, Kuwayama K, Satomi J, Nagahiro S
  • Organizer: 9th World Stroke Congress
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2014-10-22 – 2014-10-25
• [Presentation] Role of hyperhomocysteinemia in the development of intracranial aneurysms (2013)
  • Author(s): Korai M, Kung DK, Kitazato KT, Matsushita N, Tada Y, Yagi K, Shimada K, Kanematsu Y, Satomi J, Nagahiro S
  • Organizer: Congress of Neurological Surgeons 2013
  • Place of Presentation: Moscone West Convention Center (San Francisco, USA)
• [Presentation] Down-regulation of Vascular Na+/k+ ATPase in Oophorectomized Rats Feeding a High Salt Diet is Associated With The Cerebral Aneurysm Formation (2013)
  • Author(s): N.Matsushita, et al.
  • Organizer: International STROKE Conference 2013
  • Place of Presentation: ヒルトンハワイアンビレッジ（アメリカ合衆国）
• [Presentation] Imbalance Between Activation of Matrix Metalloprotease and Its Inhibition May Facilitate the Growth of Cerebral Aneurysm in Female Rats (2013)
  • Author(s): Kohrai M, et al.
  • Organizer: International STROKE Conference 2013
  • Place of Presentation: ヒルトンハワイアンビレッジ（アメリカ合衆国）