- A new model provides an unprecedented view of how vascular system of the brain controls metabolic functions.
- It’s made up of organs-on-chips that simulate functions of living human organs.
- Each organ chip contains a flexible polymer about the size of a computer memory stick.
The human brain consists of more than 86 billion neurons, and a less or more equal number of other cells that control every action, word and thought. The complete circuitry is managed by a process called neurotransmission.
The connection of blood vessels with the brain is extremely complex: these vessels carry only specific molecules (like nutrients and oxygen) from blood to brain and vice versa. The unique network of blood cells supporting astrocyte and pericyte cells is comprised of the blood-brain barrier (BBB). When this barrier is distorted — by taking drugs like methamphetamine — the sensitive neurons of the brain become vulnerable to noxious damage.
For years, scientists have been trying to figure out how the brain cells and BBB cells influence each other. Recently, a team of researchers from the Harvard’s Wyss Institute developed a model of Brain-BBB interface that provides an unprecedented view of how vascular system of the brain controls metabolic functions.
Human Organs On Microchips
Since the human brain is the most complex body part, it can’t be examined on a single organ chip. Therefore, researchers split one organ into several chips. It’s a multi-channel 3D microfluidic cell culture chip that simulates functions of living human organs.
Each organ chip contains a flexible polymer about the size of a computer memory stick that consists of hollow microfluidic channels lined by living organ-specific cells. These organ chips uncover a whole new level of interactions between the several structures within the brain.
The Brain-BBB artificial system is made of 3 chips that are linked via microfluidic channels to exchange various types of molecules between them.
- Influx BBB chip
- Brain chip
- Efflux chip
Once the channel of BBB chip is lined with endothelial cells that carry culture medium, mimicking blood, it’s isolated by a parallel channel comprising of astrocytes and pericytes, which is perfused with aCSF (artificial CerebroSpinal Fluid). In brain chip, a similar type of aCSF flow channel is isolated by a porous membrane from a region containing brain neurons and their associated astrocytes.
One Brain chip (top) connected to two BBB via microfluidic channels | Credit: Harvard’s Wyss Institute
The aCSF channels of all 3 chips are linked in a series, forming a fully connected system that mimics the brain tissue.
Experiments and Results
When the Brain-BBB chips were exposed to methamphetamine (causes distortion between cells’ junctions), it affected the junctions of vascular endothelial cells of BBB and enabled the passage of substances into the brain chip, which otherwise would not be able to pass the BBB.
This confirmed that the Brain-BBB interface worked and it could be used in future studies to better understand the effects of different drugs on the human brain.
Methamphetamine (left) disrupts junction (green) between BBB | Credit: Harvard’s Wyss Institute
The researchers also noticed that the cells in unlinked chips expressed lower levels of proteins associated with metabolism and higher levels of proteins involved in migration and proliferation than connected Brain-BBB chip cells. This indicates that the different types of cells work together to maintain proper function.
They also discovered that the production of GABA (gamma-Aminobutyric acid) and glutamine was higher in the brain chips connected with BBB than unlinked brain chips. This suggests that the mind function could be influenced by the health of blood vessels.
In the next study, researchers will use sophisticated organ chips to investigate how vascular endothelial cells impact certain functions of other organs in the human body.