Mini 'arteries-on-a-chip' could help predict a person's risk of stroke

 Have your competent? doctor lay out a path to stroke recovery with all this chip based research.

• BBB on a chip (1 post to February 2017)
• Brain on a chip (9 posts to October 2012)
• Lab on a Chip (3 posts to May 2012)

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

Mini 'arteries-on-a-chip' could help predict a person's risk of stroke

Researchers have pioneered a way to create miniaturized copies of a person's carotid artery that could help doctors predict and manage the patient's stroke risk, a new study suggests.

In the research, published in July in the journal Cell Biomaterials, scientists used these "arteries-on-a-chip" to monitor how real blood flows through a patient's carotid arteries, which carry blood to the brain, face and neck. This could enable doctors to identify not just how and what type of clots form in that specific patient, but also determine which medications would be most effective in dealing with the blockage.

While the technique is currently a proof-of-concept, someday, it could help medical practitioners to better tailor treatments for each patient.

"When the inner lining of an artery is damaged, material underneath the cells, including collagen, becomes exposed to the blood," Zhao said. A bloodborne protein called von Willebrand factor (VWF) grabs hold of platelets from the flowing blood. Those platelets then stick together and recruit more platelets, building a clot, he said.

But forming a clot is only half the story; it's what this mass does next that determines the risk to the patient.

In some cases, the growing ball of clotted blood will stay firmly rooted to the artery wall, slightly impeding blood flow but not posing any immediate danger. However, if tiny fragments break off this static clot, they can travel toward the brain, where they risk blocking smaller vessels and thus causing a stroke.

"Clinically, we are very good at imaging how narrow an artery is," Zhao said, "but narrowing alone does not tell us exactly how a clot will behave."

This is where artery-on-a-chip models come in, he said. Rather than relying purely on medical scans, the team's model recreates the exact shape and structure of an individual patient's blood vessels using 3D printing. To create the models, they first use a patient’s existing CT scans to 3D print a plastic replica of their carotid artery, including any narrowing caused by atherosclerosis. Next, the inside of this plastic structure is coated with collagen, and then cells that line the carotid artery get layered on top. Blood is passed through the replica artery, mimicking the speed and pressure of blood flow in the body.

Blood-Brain Barrier on a Chip Sheds New Light on 'Silent Killer'

For when we actually need to get drugs thru the blood brain barrier that can help improve neuroplasticity and neurogenesis.  I wonder what researcher is working on kickstarting neuroplasticity and neurogenesis?
http://www.rdmag.com/news/2016/12/blood-brain-barrier-chip-sheds-new-light-silent-killer?et_cid=5717649&

The blood-brain barrier is a network of specialized cells that surrounds the arteries and veins within the brain. It forms a unique gateway that both provides brain cells with the nutrients they require and protects them from potentially harmful compounds.

An interdisciplinary team of researchers from the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) headed by Gordon A. Cain University Professor John Wikswo report that they have developed a microfluidic device that overcomes the limitations of previous models of this key system and have used it to study brain inflammation, dubbed the "silent killer" because it doesn't cause pain but contributes to neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. Recent research also suggests that it may underlie a wider range of problems from impaired cognition to depression and even schizophrenia.
The project is part of a $70 million "Tissue Chip for Drug Testing Program" funded by the National Institutes of Health's National Center for Advancing Translational Sciences. Its purpose is to develop human organ-on-a-chip technology in order to assess the safety and efficacy of new drugs in a faster, cheaper, more effective and more reliable fashion.
The importance of understanding how the blood-brain barrier works has increased in recent years as medical researchers have found that this critical structure is implicated in a widening range of brain disorders, extending from stroke to Alzheimer's and Parkinson's disease to blunt force trauma and brain inflammation.
Despite its importance, scientists have had considerable difficulty creating faithful laboratory models of the complex biological system that protects the brain. Previous models have either been static and so have not reproduced critical blood flow effects or they have not supported all the cell types found in human blood-brain barriers.
Creating a blood-brain barrier on a chip
The new device, which the researchers call a NeuroVascular Unit (NVU) on a chip, overcomes these problems. It consists of a small cavity that is one-fifth of an inch long, one-tenth of an inch wide and three-hundredths of an inch thick - giving it a total volume of about one-millionth of a human brain. The cavity is divided by a thin, porous membrane into an upper chamber that acts as the brain side of the barrier and a lower chamber that acts as the blood or vascular side. Both chambers are connected to separate microchannels hooked to micropumps that allow them to be independently perfused and sampled.
To create an artificial blood-brain barrier, the researchers first flip the device over so the vascular chamber is on top and inject specialized human endothelial cells. They found that if they maintain a steady fluid flow through the chamber during this period, the endothelial cells, which left to themselves form shapeless blobs, consistently orient themselves parallel to the direction of flow. This orientation, which is a characteristic of the endothelial cells in human blood-brain barrier, has been lacking in many previous models.
After a day or two, when the endothelial cells have attached themselves to the membrane, the researchers flip the device and inject the two other human cell types that form the barrier -- star-shaped astrocytes and pericytes that wrap around endothelial cells -- as well as excitatory neurons that may regulate the barrier. These all go into the brain chamber that is now on top. The porous membrane allows the new cells to make physical and chemical contact with the endothelial cells just as they do in the brain.
The researchers were able to purchase the human endothelial cells, astrocytes and pericytes that they need from commercial sources. For the excitatory neurons required, they turned to Vanderbilt University Medical Center collaborators M. Diana Neely, research associate professor of pediatrics, and Aaron Bowman, associate professor of pediatrics, neurology and biochemistry. Starting with human induced pluripotent stem cells that are generated directly from adult cells they were able to produce the specialized neurons that the project needed.
"This is one of the most exciting projects I'm involved with," said Neely. "Although it's still in its infancy, it has tremendous potential."
According to Bowman, one potential application is to develop tissue chips that contain cells from individual patients, making it possible to predict their personal reactions to different drugs.
Device passes tests with flying colors
"Once we had successfully created the artificial barrier, we subjected it to a series of basic tests and it passed them all with flying colors. This gives us the confidence to state that we have developed a fully functional model of the human blood-brain barrier," said VIIBRE staff scientist Jacquelyn Brown, who is first author of the paper "Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor" that described this achievement in the journal Biomicrofluidics.
"The NVU has reached the point where we can begin using it to test different drugs and compounds," observed team member Donna Webb, associate professor of biological sciences who is interested in studying how different substances affect synapses -- the junctions between neurons. "There is an urgent need for us to understand how various substances affect cognitive processes. When we do, we will be in for a number of surprises!
Providing the first continuous picture of inflammation response
Already, the VIBRE team has used the NVU to overcome a basic limitation of existing studies of brain inflammation, which have only produced snapshots of the process at various stages. Because the NVU can be continuously monitored, it has provided the first dynamic view of how the brain and blood-brain barrier respond to systemic inflammation.
These results are summarized in a paper titled "Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit" accepted for publication in the Journal of Neuroinflammation.
The scientists exposed the NVU to two different compounds known to induce brain inflammation: a large molecule found on the surface of certain bacteria called lipopolysaccharide and a "cocktail" of small proteins called cytokines that play an important role in immune response to inflammation.
"One of our biggest surprises was the discovery that a critical component in the blood-brain barrier's response to these compounds was to begin increasing protein synthesis," said Brown. "Next will be to find out which proteins it is making and what they do."
The researchers also found that the blood vessels in the barrier respond to inflammation by pumping up their metabolic rate while the metabolism of the brain cells slows down. According to Brown, "It might be that the vasculature is trying to respond while the brain is trying to protect itself."

Draper Laboratory developing “Brain-on-a-Chip”

written up in a Virtual-Strategy magazine here:
http://www.virtual-strategy.com/2012/10/23/draper-laboratory-developing-%E2%80%9Cbrain-chip%E2%80%9D

The actual research abstract here:
http://pubs.rsc.org/en/content/articlelanding/2012/lc/c2lc41033h
In this work, we describe the fabrication and working of a modular microsystem that recapitulates the functions of the “Neurovascular Unit”. The microdevice comprised of a vertical stack of poly (dimethylsiloxane) (PDMS) neural parenchymal chamber separated by a vascular channel via a microporous polycarbonate (PC) membrane. The neural chamber housed a mixture of neurons (~4%), astrocytes (~95%), and microglia (~1%). The vascular channel was lined with a layer of rat brain microvascular endothelial cell line (RBE4). Cellular components in neural chamber and vascular channel showed viability (>90%). The neural cells fired inhibitory as well as excitatory potentials following 10 days of culture. The endothelial cells showed diluted-acetylated low density lipoprotein (dil-a-LDL) uptake, expressed von Willebrand factor (vWF) and zonula occludens (ZO-1) tight junctions, and showed decreased Alexafluor™-conjugated dextran leakage across their barrier significantly compared with controls (p < 0.05). When the vascular layer was stimulated with TNF-α for 6h, about 75% of resident microglia and astrocytes on the neural side were activated significantly (p < 0.05 compared to controls) recapitulating tissue-mimetic responses resembling neuroinflammation. The impact of this microsystem lies in the fact that this biomimetic neurovascular platform might not only be harnessed for obtaining mechanistic insights for neurodegenerative disorders, but could also serve as a potential screening tool for central nervous system (CNS) therapeutics in toxicology and neuroinfectious diseases.

I wonder how much different it is than the
Lab on a Chip?

New technology facilitates studies of brain cells in stroke

A way to listen in on the communications of individual cells. I wonder if it is better than  nanowires?
http://www.alphagalileo.org/ViewItem.aspx?ItemId=71054&CultureCode=en
A mini-laboratory that makes it possible, among other things, to study how brain cells in stroke patients are affected by lack of oxygen is being developed by a research team at Luleå University of Technology (LTU) in Sweden. Lab on a Chip is what the scientists are calling their mini-lab, which is expected to facilitate studies of all sorts of biological cells and how they are affected by different medicines, chemical substances, etc.

The researchers in medical technology at Luleå University of Technology have wind in their sails. New technological solutions are needed to help meet Europe’s rapidly growing needs for healthcare.

The development of the mini-lab Lab on a Chip is one of 22 projects being pursued within the framework of the Center for Medical Technology and Physics, CMTF, a joint initiative involving Luleå University of Technology and Umeå University.

Professor Olof Lindahl and his research associate Kerstin Ramser in Luleå are developing a so-called micro-flow system to study, for instance, how the vital oxygen-bearing protein neuroglobin,  which is found in brain cells, is affected by the lack of oxygen that occurs in stroke.

Neuroglobin was discovered in 2000 by a German research team and occurs primarily in brain cells. Overproduction of neuroglobin in the brains of mice has been shown to mitigate the consequences of damage relating to oxygen deficiency in stroke.

“Today there are no really good methods for studying how individual cells signal under oxygen-poor conditions,” says Kerstin Ramser. “One advantage of the new technology we use is that it is now possible to select and isolate specific cells in a controlled environment.”

The Lab on a Chip that the Luleå researchers have produced measures 2 X 6 cm and fits on the specimen glass of a microscope. This makes it possible to reduce the size of the sample, in blood analysis, for example.

“What we are studying is the electrophysiological activity of brain cells, that is, their capacity to communicate with other cells under oxygen-poor and entirely oxygen-free conditions,” says Kerstin Ramser.

To be able to study how brain cells are affected by stroke, researchers pump fluids with varying levels of oxygen content into channels in the mini-lab. The channels are extremely small, corresponding to one third of the thickness of a hair. Once the fluid has been pumped into the system, the cell sample is introduced. With the help of optical tweezers, which use laser beams to capture and move cells, the scientists can select and isolate a specific cell in order to study how it behaves in various oxygen mixtures.

“Enhance the quality of care today is largely a matter of developing new technologies that help us advance our knowledge of the major diseases, such as cancer, stroke, or Parkinson’s,” says Kerstin Ramser.

There are some 8 professors and 20-25 researchers in the field of medical technology at Luleå University of Technology today. Much of the medical technology research conducted at Luleå University of Technology is done together with researchers from Umeå University in an interdisciplinary collaboration where Luleå provides the technological expertise and Umeå the medical competence.

The research center CMTF involves not only the two universities but also the Norrbotten and Västerbotten County Councils, companies, and researchers from Sweden, Japan, Germany, Spain, and other countries. They develop products and services for more secure healthcare.

Their work is partly funded by EU Goal2. A researcher-owned company for developing businesses, financed by the County Administrations, Innovation Bridge North, LTU Holding, Uminova Innovation, and the parties involved, is tied to the Center.