Profile analysis of gene expressions for cereberal vasospasm

• Project/Area Number: 13671472
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: KASUYA Hidetoshi TWMU, Neurosurgery, Assistant Prof., 医学部, 講師 (50169455)
• Co-Investigator(Kenkyū-buntansha): SASAHARA Atsushi TWMU, Neurosurgery, Lecturer, 医学部, 助手 (40287371) ; ONDA Hideaki TWMU, Neurosurgery, Lecturer, 医学部, 助手 (60185692) ; 米山 琢 東京女子医科大学, 医学部, 助手 (90318105) ; 佐々木 寿之 東京女子医科大学, 医学部, 助手 (80287375)
• Project Period (FY): 2001 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,100,000 (Direct Cost: ¥3,100,000); Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: subarachnoid hemorrhage / cerebral vasospasm / gene expression

Research Abstract

Introduction : We sought to identify genes with differential expression in cerebral vasospasm after subarachnoid hemorrhage. This study was undertaken to identify hemolysate-induced differential gene expression in human vascular smooth muscle cells (HVSMC) with cDNA microarray (12814 genes).
Methods : Total ribonucleic acid (RNA) was isolated from hemolysate treated and non-treated HVSMC. Total RNAs were used to quantify lesion-specific mRNA expression levels on cDNA microarray (days 0-5). The expression of 30 genes greater than 4 fold with cDNA microarray was confirmed with real-time RT-PCR (days 0-5).
Result : There was significant up-regulation (greater than 2 fold expression) of 397 genes in the hemolysate treated cells on day 1, 49 genes on day 2, 23 genes on day 3, 31 genes on day 5. The functions of differentially expressed genes included the regulation of inflammation, membrane proteins and receptors, kinase, cell proliferation, and phosphatases. 11924 genes did not change significantly (0.5-2 fold) or did not express, and 74 genes were down-regulated (lower than 0.5 fold) on day 2. The expressions of inflammatory cytokines/chemokines such as interleukin(IL)-8, IL-1β were extremely increased on day 2, followed by gradual decline when measured with real-time RT-PCR serially.
Conclusion : We identify numerous genes that are differentially expressed in control and hemolysate-treated cells. The up-regulation of genes related to inflammatory cytokines/chemokines and its time course in HVSMC suggest that they may play a significant role in vasospasm.

Research Products

• [Publications] Kasuya H, Onda H, Yoneyama T et al.: "Bedside monitoring of circulating blood volume after subarachnoid hemorrhage"Stroke. 34. 956-960 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hiyama H, Kasuya H, Dan S, et al.: "Orbital syndorome after a surgery of restibular schwannoma via middle fossa approach"Acta Neurochir(Wien). 145. 83-85 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Onda H, Kasuya H, Yoneyama T et al.: "Endoglin Is Not a Major Susceptibility Gene for Intracranial Aneurysm Among Japanese"Stroke. 34. 1640-1644 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yoneyama T, Kasuya H, Onda H, et al.: "Association of positional and functional candidate genes FGF1,FBN2,and LOX on 5q31 with intracranial aneurysm"J Ham Genet. 48. 309-314 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yoneyama T, Kasuya H, Onda H, et al.: "Collagen Type Iα2 (COL1A2) Is the Susceptible Gene for Intracranial Aneurysms"Stroke. 35. 443-448 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sasaki T, Kasuya H, Onda H, et al.: "Role of p38 Mitogen-Activated Protein Kinase on Cerebral Vasospasm After Subarachnoid Hemorrhage"Stroke. in press. (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kasuya H, Onda H, Yoneyama T, Sasaki T, Hori T: "Bedside monitoring of circulating blood volume following subarachnoid hemorrhage."Stroke. 34. 956-960 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hiyama H, Kasuya H, Dan S, Hori T: "Orbital syndrome after a surgery of vestibular schwannoma via middle fossa approach."Acta Neurochir (Wien). 145. 83-85 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Onda H, Kasuya H, Yoneyama T, Hori T, Nakajima T, Inoue I: "Endoglin is not a major susceptibility gene for intracranial aneurysm among Japanese."Stroke. 34. 1640-1644 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yoneyama T, Kasuya H, Onda H, Akagawa H, Jinnai N, Nakajima T, Hori T, Inoue I: "Association of positional and functional candidate genes FGF1, FBN2, and Lox on chromosome 5q31 with intracranial aneurysm."J Hum Genet. 48. 309-314 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yoneyama T, Kasuya H, Onda H, Akagawa H, Hashiguchi K, Nakajima T, Hori T, Inoue I: "Collagen type I_2 (COL1A2) is the susceptible gene for intracranial aneurysms."Stroke. 35. 443-448 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sasaki T, Kasuya H, Sasahara A, Onda H, Goto S, Hori T, Inoue I: "Role of p38 mitogen-activated protein kinase on cerebral vasospasm following subarachnoid hemorrhage."Stroke. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kasuya H, Onda H, Yoneyama T, et al.: "Bedside Monitoring of Circulating Blood Volume After Subarachnoid Hemorrhage"Stroke. 34. 956-960 (2003)
• [Publications] Hiyama H, Kasuya H, Dan S, et al.: "Orbital syndrome after a surgery of vestibular schwannoma via middle fossa approach"Acta Neurochir (Wien). 145. 83-85 (2003)
• [Publications] Onda H, Kasuya H, Yoneyama T, et al.: "Endoglin is not a major susceptibility gene for intracranial aneurysm among Japanese"Stroke. 34. 1640-1644 (2003)
• [Publications] Yoneyama T, Kasuya H, Onda H, et al.: "Association of positional and functional candidate genes FGF1, FBN2, and LOX on chromosome 5q31 with intracranial aneurysm."J Hum Genet. 48. 309-314 (2003)
• [Publications] Yoneyama T, Kasuya H, Onda H. et al.: "Collagen Type I α2 (COL1A2) Is the Susceptible Gene for Intracranial Aneurysms."Stroke. 35. 443-448 (2004)
• [Publications] Sayaki T, Kasuya H, Onda H, et al.: "Role of p38 Mitogen-Activated Protein Kinase on Cerebral Vasospasm After Subarachnoid Hemorrhage"Stroke. (in press). (2004)
• [Publications] Kasuya H: "Statistical techniques and vasopasm"J Neurosurg. 96. 381 (2002)
• [Publications] Kasuya H et al.: "Efficacy and safety of nicardipe prolonged-release implants"Stroke. 33. 1011-1015 (2002)
• [Publications] Abe Y, Kasuya H, et al.: "Effect of a platelet-activating factor (PAF) antagonist"Eur J Pharmacol. 455. 127-133 (2002)
• [Publications] Kasuya et al: "Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage"Acta Neurochir[Suppl]. 77. 13-16 (2001)
• [Publications] Kasuya et al: "Development of nicardipine prolougest-release implants for preventing vasospasm"Acta Neurochir[Suppl]. 77. 217-220 (2001)
• [Publications] Onda, Kasuya, et al: "A genome-wide scan for intracranial aneurysms and a possible involvement of plastin gene"Am J Hum Genet. 69. 804-819 (2001)