Effect of statins on the blood-brain barrier

• Project/Area Number: 21591848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: 独立行政法人国立病院機構長崎医療センター (2011); Department of Clinical Research, National Hospital Organization Nagasaki Medical Center (2009-2010)
• Principal Investigator: MOROFUJI Yoichi 独立行政法人国立病院機構長崎医療センター, 臨床研究センター, 客員研究員 (40437869)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Kentaro 長崎大学, 医学部歯学部付属病院, 助教 (40404222) ; SO Gohei 長崎大学, 医学部歯学部付属病院, 医員 (80530427) ; TAKAHATA Hideaki 独立行政法人国立病院機構, 長崎医療センター・脳神経外科, 医師 (80607854) ; TAKESHITA Tomonori 長崎大学, 医学部歯学部付属病院, 医員 (30597365)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: スタチン / 血液脳関門 / タイトジャンクション / 脳卒中 / blood-brain barrier / statins / tight junctions / stroke / claudin-5 / brain endothelial cells

Research Abstract

We investigated the effect of pitavastatin on barrier functions of an in vitro BBB model with primary cultures of rat brain capillary endothelial cells(RBEC). Our data indicate that pitavastatin strengthens the barrier integrity in primary cultures of RBEC. The BBB-stabilizing effect of pitavastatin may be mediated partly through inhibition of the mevalonate pathway and subsequent up-regulation of claudin-5 expression.

Research Products

• [Journal Article] 破裂急性期にバルーン閉塞試験を行い母血管閉塞が可能であった錐体部巨大内頚動脈瘤破裂の1例 (2012)
  • Author(s): 竹下朝規、堀江信貴、宗剛平、氏福健太、林健太郎、森川実、陶山一彦、永田泉
  • Journal Title: No Shinkei Geka Volume: 40(1) Pages: 61-66
• [Journal Article] Cilostazol rescues the BBB from AGE-related Ischemic insult (2012)
  • Author(s): Tomonori Takeshita
  • Journal Title: J Pharmacol Sci Volume: 118 Pages: 142-142
• [Journal Article] 頚動脈血行再建術における術前血小板凝集能測定の有用性 (2011)
  • Author(s): 諸藤陽一、宗剛平、日宇健、川久保潤一、林健太郎、北川直毅、森川実、陶山一彦、永田泉
  • Journal Title: No Shinkei Geka Volume: 39(5) Pages: 459-63
• [Journal Article] 進行する脊髄症を呈したテント部硬膜動静脈瘻の一例 (2011)
  • Author(s): 竹下朝規,宗剛平,諸藤陽一,堀江信貴、林健太郎,北川直毅,陶山一彦,永田泉
  • Journal Title: Brain and Nerve Volume: 63・6 Pages: 611-615
• [Journal Article] Significance of the T2-weighted gradient echo brain imaging in patients with infective endocarditis (2011)
  • Author(s): Yoichi Morofuji, Minoru Morikawa, Yohei Tateishi, Naoki Kitagawa, Kentaro Hayashi, Tomonori Takeshita, Kazuhiko Suyama, Izumi Nagata
  • Journal Title: Clinical Neurology and Neurosurgery Volume: 112(5) Pages: 436-40
  • NAID: 120006984566
• [Journal Article] Preoperative analysis of platelet aggregability in carotid surgery (2011)
  • Author(s): Yoichi Morofuji
  • Journal Title: No Shinkei Geka Volume: 39 Pages: 459-463
  • Peer Reviewed
• [Journal Article] The effects of candesartan on the blood-brain barrier (2011)
  • Author(s): Gohei So
  • Journal Title: J Pharmacol Sci Volume: 115 Pages: 141-141
• [Journal Article] Pitavastatin Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells (2010)
  • Author(s): Morofuji Y, Nakagawa S, So G, Hiu T, Horai S, Hayashi K, Tanaka K, Suyama K, Deli MA, Nagata I, Niwa M.
  • Journal Title: Cell Mol Neurobiol Volume: 30(5) Pages: 727-35
  • NAID: 120006984678
• [Journal Article] Recurrence of subarachnoid hemorrhage due to the rupture of cerebral aneurysms in a patient with Sjogren's syndrome Case report (2010)
  • Author(s): Hayashi K, Morofuji Y, Suyama K, Nagata I.
  • Journal Title: Neurol Med Chir(Tokyo) Volume: 50(8) Pages: 658-61
  • NAID: 10026651389
• [Journal Article] 前大脳動脈解離性動脈瘤を合併したRubinstein-Taybi症候群の1例 (2010)
  • Author(s): 石坂俊輔、宗剛平、諸藤陽一、林健太郎、北川直毅、立石洋平、森川実、陶山一彦、永田泉
  • Journal Title: BRAIN and NERVE Volume: 62(10) Pages: 1083-1088
• [Journal Article] 頸動脈ステント留置術でデバイスを用いた穿刺部止血後に総大腿動脈閉塞をきたした1例 (2010)
  • Author(s): 林健太郎、森川実、堀江信貴、諸藤陽一、宗剛平、陶山一彦、永田泉
  • Journal Title: BRAIN and NERVE Volume: 62(2) Pages: 173-176
• [Journal Article] Pitavastatin Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells (2010)
  • Author(s): Yoichi Morofuji
  • Journal Title: Cell Mol Neurobiol Volume: 30(5) Pages: 727-735
  • NAID: 120006984678
  • Peer Reviewed
• [Journal Article] Pitavastatin Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells. (2010)
  • Author(s): Yoichi Morofuji
  • Journal Title: Cell Mol Neurobiol (In press)
  • NAID: 120006984678
  • Peer Reviewed
• [Journal Article] Effect of pitavastatin on the blood-brain barrier(BBB)in vitro. (2009)
  • Author(s): Yoichi Morofuji
  • Journal Title: J Pharmacol Sci 109(Suppl 1) Pages: 94-94
• [Presentation] Cilostazol rescues the BBB from AGE-related Ischemic insult (2012)
  • Author(s): 竹下朝規
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
• [Presentation] Cilostazol rescues AGE-related ischemic BBB damage (2011)
  • Author(s): Tomonori Takeshita
  • Organizer: 14^<th> Symposium on Signal Transduction in the Blood-Brain Barriers
  • Place of Presentation: Istanbul
  • Year and Date: 2011-09-08
• [Presentation] カンデサルタンの血液脳関門に与える影響 (2010)
  • Author(s): 宗剛平
  • Organizer: 第69回日本脳神経外科学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-28
• [Presentation] STA-MCA吻合術後に進行した外頸動脈起始部狭窄症に対しステント留置術を行った症例 (2010)
  • Author(s): 諸藤陽一、高畠英昭、川原一郎、戸田啓介、堤圭介、馬場啓至、米倉正大
  • Organizer: 第106回日本脳神経外科学会九州支部会
  • Place of Presentation: 宮崎
  • Year and Date: 2010-09-25
• [Presentation] Cilostazol rescues AGE-related ischemic BBB damage (2010)
  • Author(s): Tomonori Takeshita, 他12名
  • Organizer: 14^th Symposium on Signal Transduction in the Blood-Brain Barriers
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2010-09-18
• [Presentation] 脳動脈瘤クリッピング術後にOrbital Infarction Syndromeをきたしたと考えられる2症例 (2010)
  • Author(s): 諸藤陽一、堤圭介、高畠英昭、平尾朋仁、川原一郎、戸田啓介、馬場啓至、米倉正大
  • Organizer: 第105回日本脳神経外科学会九州支部会
  • Place of Presentation: 長崎
  • Year and Date: 2010-06-26
• [Presentation] The Effects of Statins on Blood-Brain Barrier-Possibility of therapeutic option for stroke-(oral presentation) (2010)
  • Author(s): Y. Morofuji, S. Nakagawa, S. Horai, G. So, K. Tsutsumi, H. Baba, K. Suyama, I. Nagata, M. Niwa
  • Organizer: 3rd International Conference on Hypertension, Lipids, Diabetes and Stroke Prevention
  • Place of Presentation: Berlin, Germany
• [Presentation] スタチンが血液脳関門に与える影響 (2010)
  • Author(s): 諸藤陽一、中川慎介、宗剛平、林健太郎、陶山一彦、永田泉、丹羽正美
  • Organizer: 第35回脳卒中学会総会
  • Place of Presentation: 岩手
• [Presentation] 脳神経外科手術における抗血小板薬の評価-血小板凝集能測定の有用性-(シンポジウム) (2010)
  • Author(s): 諸藤陽一、宗剛平、堀江信貴、林健太郎、陶山一彦、永田泉
  • Organizer: 第39回脳卒中の外科学会総会
  • Place of Presentation: 岩手
• [Presentation] くも膜下出血後早期のウロキナーゼ脳槽洗浄が続発性正常圧水頭症に与える影響 (2010)
  • Author(s): 諸藤陽一、堤圭介、高畠英昭、平尾朋仁、戸田啓介、馬場啓至、米倉正大
  • Organizer: 第39回脳卒中の外科学会総会
  • Place of Presentation: 岩手
• [Presentation] Preoperative Platelet Aggregation Predicts Periprocedual Complications in Neuroendovascular Surgery (2010)
  • Author(s): Yoichi Morofuji, Gohei So, Takeshi Hiu, Junichi Kawakubo, Nobutaka Horie, Kentaro Hayashi, Hideaki Takahata, Naoki Kitagawa, Kazuhiko Suyama, Izumi Nagata
  • Organizer: The 10^th Korean and Japanese Friendship Conference on Surgery for Cerebral Stroke Huis Ten Bosch
  • Place of Presentation: Sasebo, Nagasaki, Japan
• [Presentation] 脳血管内治療における抗血小板療法の評価-血小板凝集能測定の有用性-(シンポジウム) (2010)
  • Author(s): 諸藤陽一,宗剛平,堀江信貴,林健太郎,川久保潤一,高畠英昭,堤圭介,北川直毅,陶山一彦,永田泉
  • Organizer: 第69回日本脳神経外科学会総会
  • Place of Presentation: 福岡
• [Presentation] The effect of candesartan on blood-brain barrier (2010)
  • Author(s): Gohei SO
  • Organizer: 13th International BBB Symposium
  • Place of Presentation: Zurich, Switzeland
• [Presentation] The Effects of Statins on Blood-Brain Barrier-Possibility of therapeutic option for stroke- (2010)
  • Author(s): Yoichi Morofuji
  • Organizer: 3rd International Conference on Hypertension, Lipids, Diabetes and Stroke Prevention
  • Place of Presentation: Berlin, Germanyベルリン、ドイツ
• [Presentation] 脳血管内治療における抗血小板療法の評価-血小板凝集能測定の有用性-(シンポジウム) (2009)
  • Author(s): 諸藤陽一,宗剛平,堀江信貴,林健太郎,高畠英昭,堤圭介,北川直毅,陶山一彦,永田泉
  • Organizer: 第26回日本脳神経血管内治療学会
  • Place of Presentation: 北九州
• [Presentation] Effects of statins on BBB functions in vitro (2009)
  • Author(s): Yoichi Morofuji
  • Organizer: 8th Cerebral Vascular Biology International Conference
  • Place of Presentation: Sendai Japan仙台、日本
• [Remarks] Medical Tribune(2010年5月27日号、p.26)新技術により確実な手術を実現術前凝集能測定で周術期合併症を予防
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  • URL: http://www.med.nagasaki-u.ac.jp/phrmch1
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