The Analysis of mechanism ofvasospasm after subarachnoid hemorrhage At the point of unknown calcium channel

• Project/Area Number: 19791014
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: AIHARA Yasuo Tokyo Women's Medical University, 医学部, 助教 (50287372)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,870,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: vasospams / subarachnoid hemorrhage / calcium channel / TRPチャンネル / クモ膜下出血 / 脳血管攣縮 / サブタイプ / 平滑筋細胞 / アゴニスト / House keeping gene / Ribosomal 18s / degenerate primer / Rea1-time quantitative PCR / Western blotting法 / patch clump手技 / In vitro transcription

Research Abstract

脳血管攣縮はくも膜下出血後に生じる脳動脈壁の持続的収縮として、その重要な要素とされた血管平滑筋の収縮機能に関しては、多方面で数多くの研究がなされてきた。その結果、平滑筋弛緩収縮機構に関与しているとされる数多くの平滑筋膜イオンチャンネルが研究対象となり、分子生物学的に同定され薬剤的効果が試みられた。その中でも細胞膜電位依存性のCaチャンネルは、最も注目されたターゲットであり機能解明も進み、多くの阻害薬が脳血管攣縮の治療薬として試みられてきたが、決定的な解決となるような効果は認められなかった。研究者自身、カルシウムチャンネルとは別のアプローチとしてKチャンネルの発現レベルでの変化の解明を試み有意義な結果は得られたが、最終的な機能解明の結論には至らなかった。 今回新たなステップとして、未知なるカルシウムチャンネルとして平滑筋収縮機能に関与するとして多分野で注目されている、受容体活性型カルシウム透過性(TRP : transient receptor potential)チャンネルを脳血管攣縮解明の糸口として、これまでの自己データを基盤に推進する。現時点では、TRPチャンネルに関しては、機能レベルの点ばかりでなく薬剤的効果についても明らかでない部分が多いが、最終的目標は、これらのTRPチャンネル拮抗薬を用いて、脳血管攣縮を治療に一石を投じることにある。

Research Products

• [Journal Article] Temporal profile of potassium channel dysfunction in cerebrovascular smooth muscle after experimental subarachnoid haemorrhage (2008)
  • Author(s): Jahromi BS, Aihara Y, Ai J, Zhang ZD, Weyer G, Nikitina E, Yassari R, Houamed KM, Macdonald RL
  • Journal Title: Neurosci Lett 440(1)(Epub) Pages: 81-6
  • Peer Reviewed
• [Journal Article] Induction of housekeeping gene expression after subarachnoid hemorrhage in dogs (2008)
  • Author(s): Aihara Y, Jahromi BS, Yassari R, Takahashi M, Macdonald RL
  • Journal Title: J Neurosci Methods 172(1)(Epub) Pages: 1-7
  • Peer Reviewed
• [Journal Article] Preserved BK Channel Function in Vasospastic Myocytes from a Dog Model of Subarachnoid Hemorrhage (2008)
  • Author(s): Jahromi BS, Aihara Y, Ai J, Zhang ZD, Weyer G, Nikitina E, Yassari R, Houamed KM, Macdonald RL
  • Journal Title: J Vasc Res 45(5) Pages: 402-415
  • Peer Reviewed
• [Journal Article] Temporal profile of potassium channel dysfunction in cerebrov ascular smooth muscle after experimental subarachnoid haemorrhage (2008)
  • Author(s): Jahromi BS, Aihara Y., et.al.
  • Journal Title: Neurosci Lett 440(1) Pages: 81-86
• [Journal Article] Induction of housekeeping gene expression after subarachnoid hemorrhage in dogs (2008)
  • Author(s): Aihara Y, Jahromi BS, et.al.
  • Journal Title: J Neurosci Methods 172(1) Pages: 1-7
• [Journal Article] Preserved BK Channel Function in Vasospastic Myocytes from a Dog Model of Subarachnoid Hemorrhage (2008)
  • Author(s): Jahromi BS. Aihara Y., et.al.
  • Journal Title: J Vasc Res 45(5) Pages: 402-415
• [Journal Article] Minimally invasive anterior interhemispheric lamina terminalis approach for craniopharyngiomas. Anatomical, hormonal, and neuropsychological considerations (2007)
  • Author(s): Hori T, Kawamata T, Aihara Y, Amano K, Kubo O
  • Journal Title: No Shinkei Geka 35(11) Pages: 1067-77
  • Peer Reviewed
• [Journal Article] Voltage-gated K(+) channel dysfunction in myocytes from a dog model of subarachnoid hemorrhage (2007)
  • Author(s): Jahromi BS, Aihara Y, Ai J, Zhang ZD, Nikitina E, Macdonald RL
  • Journal Title: J Cereb Blood Flow Metab
  • Peer Reviewed
• [Journal Article] Novel mechanism of endothelin-1-induced vasospasm after subarachnoid hemorrhage (2007)
  • Author(s): Xie A, Aihara Y, Bouryi VA, Nikitina E, Jahromi BS, Zhang ZD, Takahashi M, Macdonald RL
  • Journal Title: J Cereb Blood Flow Metab
  • Peer Reviewed
• [Journal Article] Novel mechanism of endothelin-1-induced vasospasm after subarachnoid hemorrhage. (2007)
  • Author(s): Xie A. Aihara Y, Bouryi VA. Nikitina E, Jahromi BS, Zhang ZD, Takahashi M, Macdonald RL.
  • Journal Title: J Cereb Blood Flow Metab. Oct;27(10) Pages: 1692-701
  • Peer Reviewed
• [Journal Article] Expression and function of inwardly rectifying potassium channels after experimental subarachnoid hemorrhage (2006)
  • Author(s): Weyer GW, Jahromi BS, Aihara Y, Agbaje-Williams M, Nikitina E, Zhang ZD, Macdonald RL
  • Journal Title: J Cereb Blood Flow Metab 26(3) Pages: 382-91
  • Peer Reviewed
• [Journal Article] Oculomotor nerve schwannoma mimicking ophthalmoplegic migraine (2005)
  • Author(s): Murakami T, Funatsuka M, Komine M, Hirayama Y, Suzuki H, Shishikura K, Aihara Y, Shibata K, Hori T, Kobayashi M, Osawa M
  • Journal Title: Neuropediatrics 36(6) Pages: 395-8
  • Peer Reviewed
• [Journal Article] Induction of housekeeping gene expression in vasospastic arteries after experimental subarachnoid hemorrhage (2004)
  • Author(s): Aihara Y, Kasuya H, Onda H, Sasahara A, Macdonald RL, Hori T
  • Journal Title: Proceeding of the 20^<th> spasm symposium 32(Suppl) Pages: 53-55
  • Peer Reviewed
• [Journal Article] Angiographic, hemodynamic and histological characterization of an arteriovenous fistula in rats (2004)
  • Author(s): Yassari R, Sayama T, Jahromi BS, Aihara Y, Macdonald RL
  • Journal Title: Acta Neurochirurgica 146(5) Pages: 495-504
  • Peer Reviewed
• [Journal Article] Magnesium and experimental vasospasm (2004)
  • Author(s): Macdonald RL, Curry D, Aihara Y, Zhang ZD, Jahromi BS, Yassari R
  • Journal Title: J Neurosurgery 100(1) Pages: 106-10
  • Peer Reviewed
• [Journal Article] Molecular profile of vascular smooth muscle ion channels following experimental cerebral vasospasm (2004)
  • Author(s): Aihara Y, Jahromi BS, Yassari R, Nikitina E, Agbaje-Williams M, Macdonald RL
  • Journal Title: J Cereb Blood Flow Metab 24(1) Pages: 75-83
  • Peer Reviewed
• [Journal Article] Effect of nitric oxide donor on and correlation of changes in cyclic nucleotide levels with experimental vasospasm (2003)
  • Author(s): Aihara Y, Jahromi BS, Yassari R, Sayama T, Macdonald RL
  • Journal Title: Neurosurgery 52(3) Pages: 661-7
  • Peer Reviewed
• [Journal Article] Intracisternal sodium nitroprusside fails to prevent vasospasm in nonhuman primates (2002)
  • Author(s): Macdonald RL, Zhang ZD, Curry D, Elias M, Aihara Y, Halpern H, Jahromi BS, Johns L
  • Journal Title: Neurosurgery 51(3) Pages: 761-768
  • Peer Reviewed
• [Journal Article] Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage (2001)
  • Author(s): Aihara Y, Kasuya H, Onda H, Hori T, Takeda J
  • Journal Title: Stroke 32(1) Pages: 212-217
  • NAID: 110007526176
  • Peer Reviewed
• [Journal Article] Assignment of SLC17A6 (alias DNPI), the gene encoding brain/pancreatic islet-type Na+-dependent inorganic phosphate cotransporter to human chromosome 11p14.3 (2001)
  • Author(s): Aihara Y, Onda H, Teraoka M, Yokoyama Y, Seino Y, Kasuya H, Hori T, Tomura H, Inoue I, Kojima I, Takeda J
  • Journal Title: Cytogenet.Cell Genet 92(1-2) Pages: 167-169
  • Peer Reviewed
• [Journal Article] The efficacy and safety of the nicardipine prolonged-release implant in a canine double hemorrhage model (2000)
  • Author(s): Sasahara A, Kasuya H, Kawashima A, Aihara Y, Izawa M, Hori T
  • Journal Title: No Shinkei Geka 28(12) Pages: 1071-1075
  • Peer Reviewed
• [Journal Article] Two cases of methicillin-resistant Staphylococcus aureus (MRSA) sepsis following craniotomy (2000)
  • Author(s): Kasuya H, Kikuchi K, Imamura T, Kawashima A, Aihara Y, Ochiai T, Yamaguchi K, Fukamachi K, Hori T, Shiseki M, Tozuka K
  • Journal Title: No Shinkei Geka 28(5) Pages: 429-434
  • Peer Reviewed
• [Journal Article] Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter (2000)
  • Author(s): Aihara Y, Mashima H, Onda H, Hisano S, Kasuya H, Hori T, Yamada S, Tomura H, Yamada Y, Inoue I, Kojima I, Takeda J
  • Journal Title: J Neurochem. 74(6) Pages: 2622-2625
  • Peer Reviewed
• [Journal Article] Cloning of cDNA and the gene encoding human hepatocyte nuclear factor (HNF)-3 beta and mutation screening in Japanese subjects with maturity-onset diabetes of the young (2000)
  • Author(s): Yamada S, Zhu Q, Aihara Y, Onda H., Zhang Z, Yu L, Jin L, Si YJ, Nishigori H, Tomura H, Inoue I, Morikawa A, Yamagata K, Hanafusa T, Matsuzawa Y, Takeda J
  • Journal Title: Diabetologia 43(1) Pages: 121-124
  • Peer Reviewed