| Project/Area Number |
18591692
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Niigata University |
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Principal Investigator |
FUJIWARA Naoshi Niigata University, Institution of Medicine and Dentistry, Professor (70181419)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,160,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | cerebral cortex / hippocampus / voltage-sensitive dye / intracellular calcium / P / Q-type calcium channel / ω-agatoxin IVA / GABA_A receptor / thiamylal / ω-アガトキシン / チアミラール |
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| Research Abstract |
This study aims to clarify the relationship between the P/Q-type calcium channel or the GABAA receptor and ischemic neuronal damage. Effects of a P/Q-type calcium channel blocker and GABAA receptor modulator on ischemic neuronal damage were investigated by means of spatio-temporal analyses of excitation propagation and intracellular calcium changes in cortical and hippocampal slices of the mouse brain.
(1) Electrical stimulation to layer V of a cortical slice evoked transient depolarization in the vicinity of stimulated site. Then this excitatory response propagated to layers II-III and widely expanded in these layers. Intracellular calcium level was also elevated in layers II-III. The excitation propagation and calcium elevation were inhibited by a P/Q-type calcium channel blocker ω-agatoxin IVA(50 nmol/l). These results suggest that the P/Q-type calcium channel plays an important role in excitation propagation in the cerebral cortex.
(2) Excitation propagation in both cortical and hippocampal slices was preserved in an oxygenated Krebs solution over 20 hours after their preparation. But, in slices exposed to transient in vitro ischemia (oxygen-glucose deprivation from a bathing medium) for 5 min, excitation propagation almost disappeared 18-20 hours after the ischemic exposure. This neuronal dysfunction also occurred in the slices exposed to In vitro ischemia in the presence of w-agatoxin IVA (200 nmol/l), suggesting that the neuronal dysfunction cannot be prevented by blocking the P/Q-type calcium channel.
(3) A GABA_A receptor modulator thiamylal (200 μmol/l) inhibited the excitation propagation in cortical slices. Excitation propagation was partially preserved in both cortical and hippocampal slices after the exposure to transient in vitro ischemia in the presence of thiamylal. The result suggests that the enhancement of GABA_A receptor activity protects the ischemic neuronal dysfunction in the cortex and hippocampus.
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