Induction of cereral angiogenesis and focal ischemic tolerance by pretratment with hepatocyte growth factor
| Project/Area Number |
12670619
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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 |
Neurology
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| Research Institution | Tokai University |
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Principal Investigator |
NAGAYAMA Masao Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (80208058)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Hiroshi Tokai University, School of Mdicine, Assistant Researcher, 医学部, 助手 (20317811)
NAGAYAMA Tomiko Tokai University, School of Mdicine, Assistant Researcher, 医学部, 助手 (80266395)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | heppatocyte growth factor / HGF / angiogenesis / focal cerebral ischemia / cerebra1 infarction / ischemic tolerance / 脳虚血 |
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| Research Abstract |
1 Introduction (1) To identify genes important not only for brain injury, but also for repair and recovery, we need tissue samples at even later time periods poststroke. (2) One gene that may play a role in stroke recovery is hepatocyte growth factor(HGF). The rationale for studying HGF is that it is involved in angiogenesis, mitogenesis, and neurotrophic activities.
2 Subjects and Methods (1) Postischemic expression and localization of HGF were examined in mice (male C57BL/6N) brain up to 28 days after direct permanent middle cerebral artery (MCA) occlusion by using immunohistochemistry (n=17) and RT-PCR (n=28). (2) We introduced early pretreatment with intracisternal administration of human recombinant HGF (Mitsubishi Pharma Corporation). HGF was injected 14 days before MCA occlusion (early pretreatment, n=6), or after MCA occlusion (posttreatment, n=6), and compared with control (n=5). Mice were sacrificed at 6 days poststroke.
3 Results (1) We found extraordinarily delayed expression of both protein and mRNA of HGF predominantly in the periinfarct region. Upregulation of them reached peak at 2 wks and 2-4 wks poststroke, each. (2) Early pretreatment with HGF significantly reduced stroke size (max. -44%) and enhanced functional recovery, which was equal to or even better than posttreatment. Neurological deficits 24 hrs poststroke in early pretreatment group were significantly better than other groups.
4 Conclusions (1) Because temporal profiles of HGF expression may correspond to the process of postischemic brain tissue repair with angiogenesis and neurotrophic activities, our findings suggest a critical role of HGF in functional brain recovery. (2) Interventions aimed at superdelayed gene/protein expression may allow pharmacological induction of ischemic tolerance and/or enhanced functional recovery.
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Report
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Research Products
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