Measuring Changes in Brain Endothelial Barrier Integrity with Two Impedance-based Biosensors in Response to Cancer Cells and Cytokines

Akshata Anchan; James J.W. Hucklesby; E. Scott Graham; Catherine E. Angel

doi:10.3791/65959

がん細胞とサイトカインに応答した2つのインピーダンスベースバイオセンサーによる脳内皮バリア完全性の...

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Measuring Changes in Brain Endothelial Barrier Integrity with Two Impedance-based Biosensors in Response to Cancer Cells and Cytokines

がん細胞とサイトカインに応答した2つのインピーダンスベースバイオセンサーによる脳内皮バリア完全性の変化の測定

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09:38 min

September 22, 2023

DOI: 10.3791/65959-v

Akshata Anchan^1,2, James J.W. Hucklesby^2,3, E. Scott Graham^1,2, Catherine E. Angel³

¹Department of Molecular Medicine and Pathology, School of Medical Sciences,University of Auckland, ²Centre for Brain Research,University of Auckland, ³School of Biological Sciences,University of Auckland

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Overview

This research investigates the integrity of the blood-brain barrier mediated by brain endothelial cells through the deployment of impedance-based biosensors. Using an in vitro model, we analyze cancer cell interactions and their impact on barrier strength.

Key Study Components

Research Area

Cerebral microvasculature
Blood-brain barrier
Cellular interactions in cancer

Background

Brain endothelial cells control molecular flow into the brain.
Impedance-based technologies help assess barrier integrity.
Metastatic cancers can disrupt endothelial cell functions.

Methods Used

Impedance-based biosensors (ECIS, cellZscope)
In vitro brain endothelium models
Treatment assessment involving cytokines and cancer cells

Main Results

Cancer cells significantly reduce barrier resistance.
Transient effects of cytokines on the barrier were observed.
Optimized protocols improved experimental reproducibility.

Conclusions

This study illustrates the mechanisms by which metastatic cancer affects brain endothelial integrity.
The findings are crucial for developing therapeutic strategies to protect the blood-brain barrier in disease contexts.

Frequently Asked Questions

What is the significance of the blood-brain barrier?

The blood-brain barrier protects the brain from harmful substances while regulating the entry of necessary molecules.

How do impedance-based biosensors work?

These biosensors measure changes in electrical impedance to evaluate cellular barrier functions in real-time.

What are the effects of cancer cells on brain endothelial cells?

Cancer cells can profoundly disrupt the integrity of brain endothelial barriers, allowing for increased permeability.

What role do cytokines play in this study?

Cytokines were evaluated for their impact on the endothelial barrier's resilience, showing transient effects.

What modifications were made to improve the methodology?

The study details several years of refinements to increase the reproducibility and robustness of the biosensor techniques.

What does the experiment measure specifically?

The experiment quantitatively assesses the resistance of brain endothelial cell monolayers under various treatment conditions.

What implications do the findings have for future research?

The results indicate potential targets for therapy aimed at protecting the blood-brain barrier in cancer treatments.

ここでは、インピーダンスベースのバイオセンサーであるECISとcellZscopeを使用して、脳内皮バリア強度を測定する手法を示します。脳内皮の in vitro モデルにさまざまな刺激を追加する準備と技術について詳しく説明します。私たちは、調査結果を測定し、記録し、代表的な分析を行います。

私たちの研究は、脳の微小血管系と血液脳関門に焦点を当てています。脳内皮細胞は、脳への分子の流れを調節します。インピーダンスベースのバイオセンサーを使用して、疾患におけるバリアの完全性を評価します。

同時解析と複数の治療変数により、いくつかのがん細胞株が脳内皮を破壊することをすでに立証しています。重要なことに、これは主にプロテアーゼやサイトカインによって媒介されるのではなく、がん関連の小胞体の機能である可能性があることを立証しました。私たちは、転移性がんがどのようにして脳内皮細胞を破壊し、脳に侵入し、二次腫瘍を形成するのかを研究しています。

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