Study on the therapy against post-ischemic reperfusion brain injury using neutralizing monoclonal antibody
| Project/Area Number |
06671379
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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 |
Cerebral neurosurgery
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| Research Institution | Kanazawa University |
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Principal Investigator |
IKEDA Kiyonobu Kanazawa University, Department of Neurosurgeery, Assistant Professor, 医学部・付属病院, 講師 (80126565)
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| Co-Investigator(Kenkyū-buntansha) |
KIDA Sin-ya Kanazawa University, Department of Neurosurgeery, Assistent, 医学部・付属病院, 助手 (10214826)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | adhesion molecule / brain ischemia / reperfusion injury / monoclonal antibody / L-selectin / E-selectin / L-セレクチン / E-セレクチン / セレクチン / 中和抗体 |
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| Research Abstract |
The effects of the anti-L selectin antibody on expression of E selectin were studied in a rabbit model of post-ischemic brain reperfusion. Anesthetized rabbits underwent 2.5 hours occlusion of the internal carotid, middle cerebral, and anterior cerebral artery with the trans-orbital approach, followed by 3 and 6 hours reperfusion. Just after the start of reperfusion, they were treated with either i.v.2 mg of anti-L selectin neutralizing antibody (treated group) or normal saline (untreated group). For these 2 groups, 1)the immunohisto-pathological study was carried out for evaluating the localization of the expressed E-selectin (Endothelial Leukocyte Adhesion Molecule : ELAM-1), and 2)The northern blotting was done for evaluating the expression of ELAM-1 mRNA with the single strand DNA probe of ELAM-1 by RT-PCR cloning using the oligonucleotide primer.
Immmunohistopathologically, ELAM-1 expressed more strongly in the infarct area and its neighbor 3 hours after reperfusion than 6 hours. And it expressed not only in the small vessels but also in the cytoplasm of astrocytes and neurons around the infarct area. The administration of the neutralizing anti-L selectin antibody weakend the immunoreactivity to ELAM-1 in the 3 hours reperfusion model. Northern blotting showed no difference in expression of ELAM-1 mRNA between the treated group and the untreated one. In conclusion, L-selectin might play no role in upregulation of the ELAM-1 mRNA expression in the early stage of post-ischemic reperfusion brain injury. However, it might stimulate the release of ELAM-1, which is induced in the endothelial cells, astrocytes, and neurons by inflammatory cytokines and stored in them, to the extracellular space.
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Report
(3 results)
Research Products
(6 results)
