| Project/Area Number |
06404051
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Teikyo Univ.School of Med. |
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Principal Investigator |
TAMURA Akira Teikyo Univ.School of Med, Neurosurgery, Prof, 医学部, 教授 (80111532)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUNO Akira Teikyo Univ School of Med, Dept of Neurosurgery, Assistant Prof, 医学部, 講師 (00242058)
NAGASHIMA Tadashi Teikyo Univ School of Med, Dept of Neurosurgery, Prof, 医学部, 教授 (70217991)
KANEMITSU Hideaki Teikyo Univ School of Med, Neurosurgery, Assistant Prof, 医学部, 講師 (10129992)
NAKAYAMA Hitoshi Teikyo Univ School of Med, Neurosurgery, Associate Prof, 医学部, 助教授 (00147050)
NAKAGOMI Tadayoshi Teikyo Univ School of Med, Neurosurgery, Associate Prof, 医学部, 助教授 (90198052)
古屋 一英 帝京大学, 医学部, 助手 (40281373)
川合 謙介 帝京大学, 医学部, 助手 (70260924)
戸向 則子 帝京大学, 医学部, 教務職 (30192214)
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| Project Period (FY) |
1994 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥29,000,000 (Direct Cost: ¥29,000,000)
Fiscal Year 1997: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1995: ¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 1994: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | ischemic neuronal death / delayd neuronal death / apoptosis / remote neuronal damage / gene expression / MRI / sphingolipids / ceramide / ストレス蛋白質 / 神経栄養因子 / ラット / マウス / 蛋白代謝 / 黒質 / アセチルコリン / GAP-43 / c-myc / 脳温度 / 遠隔部 / apoptosis / 実質 |
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| Research Abstract |
We found that there are four types of neuronal death following cerebral ischemia, such as ultra-early-type ischemic neuronal injury in the thalamic reticular nucleus, classical acute ischemic neuronal death due to energy failure, delayd neuronal death which is considered to be related to apoptosis, slowly progressive neuronal death in remote areas from focal cerebral infarction. Mechanisms of teses types of nuronal death after cerebral ischemia were studied as follows.
We tried to detect the remote changes using MRI after MCA occlusion in the rat. Then, we found that, in areas remote from a primary ischemic lesion, there are two types of secondary degeneration with MR imaging.
Possible induction of mRNAs for proto-oncogene c-myc and s-myc and oncosupressor gene p53, which are known to induce apoptosis, and protooncogene bcl-2, which inhibits apoptosis, was examined following focal ischemia in the rat. The c-myc gene expression was rapidly and markedly induced in a timedependent manner. The results indicate a possibility that high level expression of the c-myc gene may be involved in the ischemic cellular events including apoptosis.
It is recently suggested that ceramide, generated by sphingomyelin degradation, plays a role as a second messenger in apoptosis. Level of ceremide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia. Ceramide began to increase at 6 hours of ischemia. Aminolinked fatty acids in increased ceramide were composed solely of non-hydroxy fatty acids, and stearic acid was the most prominent. Sphingomyelin, whose aminolinked fatty acids were mostly stearic acid, decreased in a time-dependent manner. The results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during early ischemia.
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