Illustration of a damaged city protected by a glowing dome, symbolizing the blood-brain barrier.

Healing Hurdles: Can We Rebuild the Brain's Protective Barrier?

"New research explores how in vitro models can help us understand and potentially overcome blood-brain barrier dysfunction after injury, offering hope for future therapies."


The blood-brain barrier (BBB) is a highly selective barrier that protects the brain from harmful substances while allowing essential nutrients to pass through. Neurological diseases and injuries can disrupt the BBB, increasing its permeability and allowing harmful substances to enter the brain, potentially leading to inflammation and further damage.

Understanding how the BBB functions and how it repairs itself after injury is crucial for developing effective treatments for neurological conditions. Researchers are increasingly turning to in vitro (laboratory) models to study these complex processes in a controlled environment. These models allow scientists to mimic the BBB and observe its response to different stimuli, such as injury or potential therapeutic interventions.

One promising approach involves using Electric Cell-Substrate Impedance Sensing (ECIS) to create and monitor in vitro BBB models. This article delves into a recent study that compares different ECIS-based wounding models, exploring their potential to replicate BBB dysfunction and recovery, ultimately paving the way for new therapeutic strategies.

ECIS: A New Window into BBB Repair

Illustration of a damaged city protected by a glowing dome, symbolizing the blood-brain barrier.

Electric Cell-Substrate Impedance Sensing (ECIS) is a technique that measures the electrical impedance (resistance) of cells grown on an electrode. By applying a controlled electrical current, researchers can monitor changes in cell behavior, such as cell migration, adhesion, and barrier function. In the context of BBB research, ECIS can be used to create "wounds" (disruptions) in a cell monolayer that mimics the BBB and then track how the cells repair the damage over time.

A recent study compared two types of ECIS arrays: single-electrode (8W1E) and multiple-electrode (8W10E+) arrays. Human cerebral microvascular endothelial cells (hCMVEC), which are key components of the BBB, were grown on these arrays, and then "wounded" using an electrical current. Researchers then monitored the cells' migration and barrier function, and analyzed the localization of junctional proteins, which are important for maintaining BBB integrity.

  • Variable Disruption: The study found that different levels of barrier disruption could be achieved by altering the duration and magnitude of the applied current.
  • Incomplete Recovery: In all scenarios, the barrier (Rb) did not fully recover to its original strength after injury.
  • Faster Migration: Cell migration was generally faster on the 8W10E+ arrays compared to the 8W1E arrays.
  • Cellular Debris: Non-viable cells remained on the 8W1E electrodes, while the 8W10E+ electrodes showed complete detachment of dead cells. However, some viable cells remained on the 8W10E+ electrodes following wounding.
  • Wounding Variation: The 8W10E+ electrodes demonstrated variation in cell loss across electrodes within the same well, suggesting that the type of wounding differed on the two array types.
These findings suggest that both single and multiple electrode arrays can be valuable tools for modeling incomplete barrier recovery and for testing drugs that could improve endothelial barrier function. The differences in wounding patterns produced by the two arrays could also be used to study the underlying causes of impaired barrier function following central nervous system (CNS) injuries.

Looking Ahead: New Hope for BBB Repair

This research highlights the potential of ECIS-based in vitro models for studying BBB dysfunction and recovery after injury. By using these models, scientists can gain a better understanding of the complex cellular and molecular mechanisms involved in BBB repair, ultimately leading to the development of new therapies to protect and restore this vital barrier.

The ability to create controlled wounds in vitro and monitor the repair process in real-time offers a significant advantage over traditional methods. These models can be used to screen potential drug candidates, identify new therapeutic targets, and personalize treatments for patients with neurological conditions.

While in vitro models have limitations, they provide a valuable platform for studying complex biological processes and for accelerating the development of new treatments. Further research is needed to validate these findings in vivo and to translate them into clinical applications, but the future looks promising for developing effective strategies to repair the blood-brain barrier and improve outcomes for patients with neurological injuries.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3390/bios8040090, Alternate LINK

Title: In Vitro Wounding Models Using The Electric Cell-Substrate Impedance Sensing (Ecis)-Zθ Technology

Subject: Clinical Biochemistry

Journal: Biosensors

Publisher: MDPI AG

Authors: Andrea Gu, Dan Kho, Rebecca Johnson, E. Graham, Simon O’Carroll

Published: 2018-10-11

Everything You Need To Know

1

What is the blood-brain barrier and why is it so important?

The blood-brain barrier (BBB) is a highly selective barrier that protects the brain from harmful substances while allowing essential nutrients to pass through. It's critical for brain health, and its disruption can lead to inflammation and further damage. The article highlights its importance, especially in the context of neurological injuries where the BBB's protective function is compromised.

2

What is Electric Cell-Substrate Impedance Sensing (ECIS) and how is it used in this context?

Electric Cell-Substrate Impedance Sensing (ECIS) is a technique used to measure the electrical impedance of cells grown on an electrode. In the context of the blood-brain barrier (BBB) research, ECIS helps create in vitro models to mimic the BBB and observe its response to injuries or therapeutic interventions. It allows researchers to monitor changes in cell behavior, such as migration and barrier function, providing insights into BBB repair processes.

3

Who are the human cerebral microvascular endothelial cells (hCMVEC) and what role do they play in the study?

Human cerebral microvascular endothelial cells (hCMVEC) are key components of the blood-brain barrier (BBB). The study used these cells to create in vitro models on ECIS arrays. hCMVEC cells form a tight barrier, and understanding their behavior in response to injury is crucial for developing therapies to repair the BBB and treat neurological conditions. The experiment involved observing hCMVEC cells' migration, barrier function, and the localization of junctional proteins after wounding.

4

What are the key differences observed between the single-electrode (8W1E) and multiple-electrode (8W10E+) arrays?

The study compared single-electrode (8W1E) and multiple-electrode (8W10E+) arrays in ECIS-based wounding models. It revealed that both types of arrays can be used to model incomplete barrier recovery. The 8W10E+ arrays demonstrated variation in cell loss, implying different wounding patterns compared to 8W1E arrays. These differences in the arrays are important for studying the underlying causes of impaired barrier function following central nervous system (CNS) injuries and testing drugs to improve endothelial barrier function.

5

What are the potential implications of this research for treating neurological conditions?

The research using Electric Cell-Substrate Impedance Sensing (ECIS) has implications for developing therapies for neurological conditions. By mimicking the blood-brain barrier (BBB) and its injury in vitro, scientists can study the repair mechanisms in a controlled environment. This understanding can lead to new therapeutic strategies to restore the BBB's function, protecting the brain from harmful substances and promoting recovery after neurological damage. The findings of the study indicate incomplete recovery and how different array types may provide insight into drug testing.

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