Development of an In Vitro Model to Study Mechanisms of Ultrasound-Targeted Microbubble Cavitation–Mediated Blood–Brain Barrier Opening

并行传输 跨细胞 血脑屏障 磁导率 微气泡 内皮干细胞 生物物理学 细胞生物学 化学 药物输送 紧密连接 体外 超声波 材料科学 生物 纳米技术 医学 神经科学 生物化学 中枢神经系统 放射科
作者
Grace E. Conway,Anurag N. Paranjape,Xucai Chen,Flordeliza S. Villanueva
出处
期刊:Ultrasound in Medicine and Biology [Elsevier]
标识
DOI:10.1016/j.ultrasmedbio.2023.12.005
摘要

Ultrasound-targeted microbubble cavitation (UTMC)-mediated blood-brain barrier (BBB) opening is being explored as a method to increase drug delivery to the brain. This strategy has progressed to clinical trials for various neurological disorders, but the underlying cellular mechanisms are incompletely understood. In the study described here, a contact co-culture transwell model of the BBB was developed that can be used to determine the signaling cascade leading to increased BBB permeability.This BBB model consists of bEnd.3 cells and C8-D1A astrocytes seeded on opposite sides of a transwell membrane. Pulsed ultrasound (US) is applied to lipid microbubbles (MBs), and the change in barrier permeability is measured via transendothelial electrical resistance and dextran flux. Live cell calcium imaging (Fluo-4 AM) is performed during UTMC treatment.This model exhibits important features of the BBB, including endothelial tight junctions, and is more restrictive than the endothelial cell (EC) monolayer alone. When US is applied to MBs in contact with the ECs, BBB permeability increases in this model by two mechanisms: UTMC induces pore formation in the EC membrane (sonoporation), leading to increased transcellular permeability, and UTMC causes formation of reversible inter-endothelial gaps, which increases paracellular permeability. Additionally, this study determines that calcium influx into ECs mediates the increase in BBB permeability after UTMC in this model.Both transcellular and paracellular permeability can be used to increase drug delivery to the brain. Future studies can use this model to determine how UTMC-induced calcium-mediated signaling increases BBB permeability.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刚刚
聪明白筠完成签到,获得积分10
1秒前
傲娇黄豆完成签到,获得积分10
1秒前
orixero应助李李李李李采纳,获得10
2秒前
_呱_完成签到,获得积分10
3秒前
szc-2000发布了新的文献求助10
5秒前
顾矜应助冷酷保温杯采纳,获得10
6秒前
6秒前
科研通AI5应助幸福大白采纳,获得10
6秒前
Orange应助幸福大白采纳,获得10
7秒前
斯文败类应助幸福大白采纳,获得10
7秒前
科研通AI5应助幸福大白采纳,获得10
7秒前
科研通AI5应助幸福大白采纳,获得10
7秒前
科研通AI5应助幸福大白采纳,获得10
7秒前
科研通AI5应助幸福大白采纳,获得10
7秒前
7秒前
8秒前
8秒前
不能随便完成签到,获得积分10
8秒前
小刘不搞科研完成签到,获得积分10
9秒前
xiaolu完成签到,获得积分10
10秒前
10秒前
共享精神应助szc-2000采纳,获得10
10秒前
Jasper应助卷卷采纳,获得10
11秒前
QX完成签到 ,获得积分10
12秒前
牛马通发布了新的文献求助10
12秒前
goovenph发布了新的文献求助10
12秒前
14秒前
14秒前
不倦应助1234采纳,获得10
15秒前
生动听筠完成签到,获得积分20
15秒前
15秒前
大观天下发布了新的文献求助10
16秒前
szc-2000完成签到,获得积分10
17秒前
赘婿应助知性的问筠采纳,获得10
18秒前
柒柒完成签到,获得积分10
18秒前
研友_VZG7GZ应助明亮无颜采纳,获得10
20秒前
旺仔小馒头完成签到 ,获得积分10
20秒前
李家新29完成签到,获得积分10
21秒前
高分求助中
Continuum Thermodynamics and Material Modelling 3000
Production Logging: Theoretical and Interpretive Elements 2700
Les Mantodea de Guyane Insecta, Polyneoptera 1000
Structural Load Modelling and Combination for Performance and Safety Evaluation 1000
Conference Record, IAS Annual Meeting 1977 820
England and the Discovery of America, 1481-1620 600
電気学会論文誌D(産業応用部門誌), 141 巻, 11 号 510
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3572635
求助须知:如何正确求助?哪些是违规求助? 3142841
关于积分的说明 9449037
捐赠科研通 2844177
什么是DOI,文献DOI怎么找? 1563386
邀请新用户注册赠送积分活动 731723
科研通“疑难数据库(出版商)”最低求助积分说明 718679