Blood-Brain Barrier on a Chip

Highlights

• Researchers have developed a dynamic blood-brain barrier device on a microchip with a volume that is one-millionth of that of a human brain.
• It is used to study the mechanism of action of the cells in the blood-brain barrier, and the mechanism involved in brain inflammation.
• Such key insights will aid in understanding neurodegenerative diseases like Parkinson’s and Alzheimer’s.
• The microfluidic device can also be used to include specific patient cells which can then be used to study individual response to medication.

The blood-brain barrier is a diffusion barrier that separates the brain from the circulatory system, protecting the central nervous system from harmful chemicals that may be potentially carried by the circulatory system. It helps in the transport of nutrient and ensures a stable environment. It is a network of special cells that include endothelial cells, astrocytes and pericytes. Researchers from Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) have developed a device that is microfluidic and which has overcome limitations faced by other such devices. This microfluidic device was designed to study inflammation that occurs in the brain.

Brain inflammation is a severe condition, also dubbed “the silent killer” due to the absence of pain associated with this condition. Brain inflammation has been found to lead to Parkinson’s, Alzheimer’s and other neurodegenerative diseases. Some studies have even shown that inflammation in the brain could lead to depression and schizophrenia.

Importance of Studying the Blood-Brain Barrier

There are a few important factors that necessitate further study into the blood-brain barrier

• The blood-brain barrier is associated with a number of medical conditions, including neurodegenerative disorders.
• It can be used to understand the trauma caused when blunt force is exerted on the head and also to study inflammation in the brain.
• Medicines are not found to cross the blood-brain barrier which results in the poor treatment of diseases associated with the brain. Studying the blood-brain barrier using microchip devices might aid in understanding the dynamics of this system and provide solutions for drug movement.
• Effective Drug Testing: This microchip device of the blood-brain barrier is a part of a $70million project that is aimed at developing human organ on a chip to study drug effectiveness faster, cheaper and more efficiently.

This microfluidic device that is designed to be a blood-brain barrier system on a chip is better than the previous models as they were static or did not contain all the cells that were part of the blood-brain barrier.

Neurovascular Unit on a Chip

The device has many advantages over the previous models and the structure dimensions are

• There is a small cavity that is 1/5th of an inch long
• 1/10th of an inch wide
• Three-hundredths of an inch thick
• The volume of the device is one millionth of a human brain
• There is a thin porous membrane that divides the cavity
• The upper portion of the cavity is the brain barrier region
• The lower side is the blood barrier

The two barriers are independently attached to microchannels which are attached to micropumps which allow individual sampling and perfusion.

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Artificial Blood-Brain Barrier:

An artificial blood-brain barrier is created by placing the device with the blood-barrier on top and then injecting the barrier with specialized endothelial cells. The endothelial cells form shapeless blobs initially, however, when a steady flow of liquid is allowed, they align themselves parallel to the flow of blood.

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When the endothelial cells get attached to the membrane over a period of two days, the device is turned over and the brain-barrier region is on top. Star shaped astrocytes and pericytes are then injected into the barrier. These cells wrap around the endothelial cells and the excitatory cells. The endothelial cells were found to cross the porous membrane and reach the brain barrier, like in the human brain.

The researchers in the study state that the technique can be modified to include individual patient cells to understand specific response to drug therapy.

The researchers conducted a lot of tests after the device was developed to understand how it functions, the device “passed with flying colors” according to Jacquelyn Brown who is the first author of the study and a VIIBRE Scientific staff.

The researchers claim that the device has reached a state of efficiency where it can be used to test various drugs. This will allow a better understanding of how cognitive processes function and will help solve mysteries that are associated with mental decline.

The device has provided a continuous model of the inflammation process as it is dynamic and can be continuously monitored. The response of the brain as well as the blood-brain barriers in response to inflammation was studied using this device.

The researchers exposed the device to a large molecule that is found on the surface of a large bacterium called lipopolysaccharide and to a group of small molecules called cytokines. The blood-brain barrier device began to increase the process of protein synthesis. As a next step, the scientists would like to determine the type of proteins that are synthesized.

The scientists identified a system in the blood-brain barrier which showed that the metabolic rate of the blood-brain barrier was increased while the metabolism of the brain slowed down. This could be an indication of the barrier responding to the inflammation while the brain protects itself.

References:

1. The blood-brain barrier: an overview: structure, regulation, and clinical implications - (https://www.ncbi.nlm.nih.gov/pubmed/15207256)

Source-Medindia