| Project/Area Number |
14571322
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
NAGAYAMA Tetsuya Kagoshima University, Graduate School of Medical and Dental Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (40336334)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Atsuro Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (60183969)
HIRANO Hirofumi Kagoshima University, University Hospital, Faculty of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (00264416)
NIIRO Masaki Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (30172612)
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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 |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | PACAP / maxadilan / ischemia / apoptosis / Max.d.4 / brain |
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| Research Abstract |
Pituitary adenylate cyclase activating polypeptide(PACAP), a pleiotropic neuropeptide, was originally isolated from ovine hypothalamic tissues.PACAP is widely distributed in the brain, and act as a neuromodulatar, neurotransmitter, neurotrophic or neuroprotective factor.On the other hand, maxadilan, a potent vasodilator peptideisolated from salivary glands of the sand fly Lutzomyia longipalpis, is a specific agonist for the PACAP type I receptor(PAC1-R).Since it is not known whether PACAP or maxadilan exerts a neuroprotective effect, we have investigated the effect of PACAP or maxadilan in rat brain in transient global cerebral ischemia and in hypoxic. neuronal cultures.PACAP and Maxadilan dose-dependently protect neuronal cell culture against hypoxia and glucose deprivation.This effect appears to be mediated through PAC1-R, because it is blocked by a selective, competitive PAC 1 -R antagonist, max.d.4.We also observed neuroprotection by maxadilan in global cerebral ischemia with maxadilan administered i.c.v(10 pmol/h)from 10 mm before to 72 hr after schemia. In addition, transient CREB phosphorylation occurred after administration of maxadilan in cultured neuron.CREB is an important transcriptional regulatory factor, and is now thought to play a crucial role in neuroprotection in various pathological conditions, including ischemia.The overall data demonstrate that maxadilan-induced activation of the several pathways such as cAMP/PKA/CREB pathway through the PAC1-R may contribute to neuroprotection against hypoxia.These results suggest thot maxadilan could be usefull in the treatment of stroke and other forms of cerebral ischemia.
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