2005 Fiscal Year Final Research Report Summary
Functional Changes in the Blood-Brain Barrier and Neuroprotective Effects in the Brain Ischemia
| Project/Area Number |
16590123
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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 |
Medical pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
DEGUCHI Yoshiharu Teikyo University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40254255)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Atsushi Teikyo University, School of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (80230415)
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| Project Period (FY) |
2004 – 2005
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| Keywords | blood-brain barrier / ammonal model for ischemia / delayed neuronal death / bFGF / FGF receptor / FGFRs-expressing cells / stroke / neuroprotection |
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| Research Abstract |
This study was to investigate functional changes in the blood-brain barrier (BBB) and mechanism for neuron protection in the ischemic brain. Firstly, the neuroprotective effects was examined in transient brain ischemia induced by bilateral carotid artery occlusion (2VO) in C57BL/6N. Secondly, it was investigated whether a novel cationic VIP analogue (cVIP) has a neuroprotective effect in transient brain ischemia after uptake into the brain through the BBB. A loss of neuronal cells in the hippocampal CA1 region of C57BL/6N mice 1 week after 2VO-reperfusion was significantly suppressed by an i.p. injection of cVIP (1.0 pmol/kg). In addition, the quantitative real-time PCR (TaqMan) and Western blot analyses revealed that FGFR1 was significantly over-expressed in the ischemic brain of C57BL/6J mice after cVIP administration. The brain uptake of ^<125>I-cVIP, evaluated by the in situ rat brain perfusion coupled with the capillary depletion method, showed that ^<125>I-cVIP underwent significant transport through the BBB. The present results suggest that cVIP may exhibit a neuroprotective effect via induction of FGFR1 after uptake into the brain through the BBB.
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