Project/Area Number |
10670584
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE |
Principal Investigator |
MATSUMOTO Masayasu Osaka University Graduate School of Medicine Associate Professor, 医学系研究科, 助教授 (20192346)
|
Co-Investigator(Kenkyū-buntansha) |
KUWABARA Keisuke Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
OHTSUKI Toshiho Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
KITAGAWA Kazuo Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70301257)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | Tyrosine phosphorvlation / cerebral ischemia / microcirculation / Apoptosis / stress protein / HSP110 / チロシンキナ-ゼ |
Research Abstract |
In order to achieve a better understanding of molecular mechanism underlying selective neuronal death, we have established a reproducible model of transient global ischemia and focal ischemia in mice and examined the involvement of microcirculatory disturbance and apoptosis in cerebral ischemia by employing ICAM-1 knockout mice and BCL-2 transgenic mice. Our results supported the notion that microcirculatory disturbance is involved in expansion of infarction after focal ischemia but not in selective neuronal death, and apoptotic mechanism may be involved in selective neuronal death following transient global ischemia. Next, we tried to identify a molecule involved in selective neuronal death. We employed the mRNA differential display method in the four vessel occlusion model in rats. Some genes were identified as candidates that encode ischemia-responsive protein, and one of them was cloned as ischemia-responsive protein 94 kDa(irp94)from the rat hippocampal cDNA library. Sequence analysis showed that rat irp94 was a novel member of the HSP110 family. irp94 mRNA was enhanced 4-24 h after ischemia and in situ hybridization histochemistry showed neuronal localization of irp mRNA. Our study suggested that irp94 might play an important role in the environmental altering neuronal functions, especially after ischemia.
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