2022 Fiscal Year Final Research Report

Analysis of mechanisms for the selective transport of physiologically active substances from the blood to the cerebrospinal fluid, with the aim of forensic pathological diagnosis

Research Project

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Project/Area Number	20K10559
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 58040:Forensics medicine-related
Research Institution	Osaka Metropolitan University (2022) Osaka City University (2020-2021)
Principal Investigator	Ishikawa Takaki 大阪公立大学, 大学院医学研究科, 教授 (50381984)
Co-Investigator(Kenkyū-buntansha)	谷直人大阪公立大学, 大学院医学研究科, 助教 (00802612) 池田知哉大阪公立大学, 大学院医学研究科, 講師 (10620883) 渡邊美穂大阪公立大学, 大学院医学研究科, 特任助教 (20845317)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	血液-脳脊髄液関門 / 血液中濃度 / 脳脊髄液濃度 / 4-AP / Energy drinks / caffeine
Outline of Final Research Achievements	Caffeine, a main ingredient in energy drinks, is known to pass easily through the blood-brain barrier. However, the dynamics of caffeine in the blood-cerebrospinal fluid barrier (BCSFB) have not been studied in detail. Alternatively, could this be either "This study found that the concentration of caffeine in the cerebrospinal fluid (CSF) decreased depending on the concentration of 4-AP. In a morphological investigation, it was also observed that choroid plexus epithelial cells appear to impede the movement of caffeine into the CSF. From these results, it is understood that when stimulant drugs and caffeine are both present at the same time, the passage of caffeine into the BCSFB is obstructed.
Free Research Field	法医学
Academic Significance and Societal Importance of the Research Achievements	剖検例における検討では，脳脊髄液に比較して血中のカフェイン濃度が高値を示した．BCSFBモデルを用いた培養実験では，4-APの濃度と投与後経過時間に依存して，カフェイン濃度が低値を示した．形態学的検討では，脈絡叢上皮細胞内に液胞の形成が観察された．BCSFBモデルにおいて血管内皮細胞と脈絡叢上皮細胞内のカフェイン濃度は，脈絡叢上皮細胞で高く検出される傾向にあることが認めらえた．それらの結果から，中枢神経刺激薬とともにカフェインが脈絡叢を通過する場合，カフェインの吸収が抑制されることが明らかとなり，抑制されたカフェインは脈絡叢上皮細胞内に貯留される可能性が示唆された．