Establishing Co-Culture Blood-Brain Barrier Models for Different Neurodegeneration Conditions to Understand Its Effect on BBB Integrity

被引：31

作者：

Park, Jun Sung ^{[1
]}

Choe, Kyonghwan ^{[1
,2
]}

Khan, Amjad ^{[1
]}

Jo, Myeung Hoon ^{[1
]}

Park, Hyun Young ^{[2
,3
]}

Kang, Min Hwa ^{[1
]}

Park, Tae Ju ^{[4
]}

Kim, Myeong Ok ^{[1
,5
]}

机构：

[1] Gyeongsang Natl Univ, Coll Nat Sci, Div Life Sci & Appl Life Sci BK21 FOUR, Jinju 52828, South Korea

[2] Maastricht Univ, Sch Mental Hlth & Neurosci MHeNs, Dept Psychiat & Neuropsychol, NL-6229 ER Maastricht, Netherlands

[3] Maastricht Univ Med Ctr MUMC, Dept Pediat, NL-6202 AZ Maastricht, Netherlands

[4] Univ Glasgow, Inst Canc Sci, Paul OGorman Leukaemia Res Ctr, Haematooncol Syst Med Grp,MVLS, Glasgow G12 0ZD, Scotland

[5] Alz Dementia Korea Co, Jinju 52828, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

BBB; in vitro model; TEER; brain endothelial cells; astrocytes; tight junction proteins; neurodegenerative diseases; IN-VITRO MODEL; AMYLOID-BETA; ALZHEIMERS-DISEASE; MEMORY DEFICITS; HYPERPHOSPHORYLATION; DYSFUNCTION; LEAKAGE; SYSTEM; CELLS; VIVO;

D O I：

10.3390/ijms24065283

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The blood-brain barrier (BBB) is a functional interface that provides selective permeability, protection from toxic substances, transport of nutrients, and clearance of brain metabolites. Additionally, BBB disruption has been shown to play a role in many neurodegenerative conditions and diseases. Therefore, the aim of this study was to establish a functional, convenient, and efficient in vitro co-cultured BBB model that can be used for several physiological conditions related to BBB disruption. Mouse brain-derived endothelial (bEnd.3) and astrocyte (C8-D1A) cells were co-cultured on transwell membranes to establish an intact and functional in vitro model. The co-cultured model and its effects on different neurological diseases and stress conditions, including Alzheimer's disease (AD), neuroinflammation, and obesity, have been examined by transendothelial electrical resistance (TEER), fluorescein isothiocyanate (FITC) dextran, and tight junction protein analyses. Scanning electron microscope images showed evidence of astrocyte end-feet processes passing through the membrane of the transwell. Moreover, the co-cultured model showed effective barrier properties in the TEER, FITC, and solvent persistence and leakage tests when compared to the mono-cultured model. Additionally, the immunoblot results showed that the expression of tight junction proteins such as zonula occludens-1 (ZO-1), claudin-5, and occludin-1 was enhanced in the co-culture. Lastly, under disease conditions, the BBB structural and functional integrity was decreased. The present study demonstrated that the co-cultured in vitro model mimicked the BBB's structural and functional integrity and, under disease conditions, the co-cultured model showed similar BBB damages. Therefore, the present in vitro BBB model can be used as a convenient and efficient experimental tool to investigate a wide range of BBB-related pathological and physiological studies.

引用

页数：17

共 76 条

[1] Astrocyte-endothelial interactions and blood-brain barrier permeability [J].