| Project/Area Number |
14370507
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Faculty of Medical Sciences, University of Fukui |
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Principal Investigator |
YOKOYAMA Osamu University of Fukui, Urology, Professor, 医学部, 教授 (90242552)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Hirokazu University of Fukui, Urology, Lecturer, 医学部附属病院, 助手 (00293431)
OYAMA Nobuyuki University of Fukui, Urology, Assistant Professor, 医学部附属病院, 講師 (20223977)
AKINO Hironobu University of Fukui, Urology, Associate Professor, 医学部, 助教授 (90159335)
MORIYAMA Norihiro University of Fukui, Urology, Lecturer, 医学部附属病院, 助手 (70313773)
TANASE Kazuya University of Fukui, Urology, Lecturer, 医学部, 助手 (00359720)
小松 和人 金沢大学, 医学部附属病院, 講師 (80291368)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥9,800,000 (Direct Cost: ¥9,800,000)
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| Keywords | Cerebrovascular accident / voiding dysfunction / neurogenic bladder / urinary incontinence / neuronal plasticity / prostaglandin / COX-2 / EP-1 |
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| Research Abstract |
Objectives : Development of bladder overactivity(BO)caused by cerebral infarction is believed to require transcription in the pontine micturition center(PMC).We previously reported that the expression of cyclooxygenase-2(COX-2) mRNA was mediated by the activity of an NMDA (N-methyl-D-aspartate) receptor in the PMC and necessary for the development of BO.This study was undertaken to examine whether the expression of prostaglandin (PG) E or D synthase, downstream gene of COX-2, and levels of PGE2 and D were related to BO induced by left middle cerebral artery (MCA) occlusion. Furthermore, the effects of NS-398, COX-2 inhibitor, and ONO-8711, EPi receptor antagonist, on BO were studied. Methods : Cerebral infarction(CI) was induced by left MCA occlusion in female SD rats. Awake rats were cystometrically examined. Specimens were obtained from the dorsal pontine tegmentum (DPi) 0.25, 1, 3, 5,12, and 24 hours after MCA occlusion or a sham operation (SO).The effects of MK-801 (0.1 mg/kg, iv),
… More
an NMDA receptor antagonist, on PGES or PGDS expression following MCA occlusion were studied. Expressions of PGES and PGDS in the DPT were monitored with real-time PCR.NS -398 or ONO-8711 was intravenously or intracerebroventriculaly administered.
Results : Bladder capacity of CI rats was significantly reduced 1-24 hours after MCA occlusion.One hour after MCA occlusion, PGES and PGDS mRNA expression had significantly increased, as compared to that in SO rats. PGES and PGDS expressions remained consistently higher than those in SO rats at least 12 hours after MCA occlusion.Pretreatment with MK-801 inhibited the development of bladder overactivity and significantly reduced the expression of PGES mRNA in the DPT.The expression of PGDS mRNA was not influenced by pretreatment with MK-801.The level of PGE2 increased 3 to S hours after MCA occlusion at the DPT. NS-398 and ONO-8711 inhibited the development of BO caused by cerebral infarction. Conclusion: These results indicate that the development of BO following M, CA occlusion is mediated by the activity of an NMDA receptor and accompanied by an increase in COX-2 and PGES mRNA expression in the DPT.PG is believed to be closely related to the BO caused by cerebral infarction. Less
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