| Project/Area Number |
26461906
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
Sato Kazushige 東北大学, 医学系研究科, 大学院非常勤講師 (40375043)
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| Co-Investigator(Kenkyū-buntansha) |
藤盛 啓成 東北大学, 大学病院, 准教授 (50238622)
西村 隆一 東北大学, 医学系研究科, 大学院非常勤講師 (90710864)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | カルシニューリンインヒビター / 中枢神経毒性 / 白質脳症 / 脳内移行 / ビリルビン / カルシニューリン阻害薬 / 脳血液関門 / カルシニューリン阻害剤 / サイトカイン / calcineurin-inhibitor / 中枢神経障害 |
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| Outline of Final Research Achievements |
We investigated the correlation between neurotoxicity and the intracerebral concentration of tacrolimus using Rats. The levels of the whole blood and the corresponding intracerebral concentration were evaluated. The threshold concentration of tacrolimus in the brain resulting in neurotoxic events was therefore estimated approximately 870 ng/g. Using a linear correlation between the whole blood and intracerebral concentrations of tacrolimus, the pharmacological threshold for the whole blood level was estimated as 28.6 ng/mL. Next, we investigated the effects of higher blood bilirubin levels to the intracerebral concentrations using galactosamine-induced liver failure rats. There was very strong correlations between the blood bilirubin levels and the intracerebral concentration of tacrolimus. Thus, the prolonged higher levels of bilirubin may alter capillary endothelial cells of blood-brain-barrier, and consequently lead to tacrolimus-associated cytotoxic injuries in the brain.
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