1995 Fiscal Year Final Research Report Summary
Role of Glial Inducible Nitric Oxide Synthase (iNOS) in Focal Brain Injury
| Project/Area Number |
06680777
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | RIKEN (The Institute of Physical and Chemical Research) |
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Principal Investigator |
KIUCHI Kazutoshi The Institute of Physical and Chemical Research (RIKEN), Bio-Mimetic Control Research Program, Head, バイオ・ミメティックコントロール研究センター, チームリーダー (30135339)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Akihide Nagoya Univ.Sch.of Medicine, Dept.of Immunology, Postgraduate, 医学部・免疫学講座, 大学院生
ISOBE Ken-ichi Nagoya Univ.Sch.of Medicine, Dept.of Immunology, Associate Professor, 医学部・免疫学講座, 助教授 (20151441)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Striatum / Microglia / iNOS / L-NAME / GDNF / Gliosis |
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| Research Abstract |
We have established a model of focal striatial injury and observed an expression of iNOS gene.A direct injection of 5-mul ethanol into rat striatum with the stereotaxic operation destroyed about one-fifth of the tissue.Expressions of genes such as immediate early genes, iNOS,cytokines and neurotrophic factors were analyzed, and their temporal and spacial patterns in the lesion were clarified. After the ethanol injection, c-fos mRNA was first detected by RT-PCR and followed by mRNAs ; IL-6, G-CSF,iNOS and CSF-1.Their expressions were maximum at 0.5,6,12,24 and 72 h, respectively.The significant increases in neurotrophic-factor mRNAs including GDNF,however, were not detected.We confirmed the iNOS induction using in situ hybridization and immunohistochemistry.Inducible NOS mRNA and its immunoreactivity were detected in microglial cells at a restricted region between necrosis and normal ares.Coincide with the iNOS expression, mRNAs of Mn-SOD and Cu/Zn-SOD were detected by in situ hybridization 24 h after the ethanol injection.SODs may protect cells in the border region from NO toxicity.Five days after the ethanol injection, there existed lots of microglial cells, which were supposed to have grown in response to CSF-1.Neurons in the border region had almost disappeared and gliosis had proceeded.In contrast, repeated intraperitoneal administrations of L-NAME,a competitive inhibitor of NOS,into rats after the ethanol injection decreased the fall off of neurons in the same region.These results suggest that NO released by microglial cells may eliminate damaged neurons in the border region between necrosis and normal area.
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