The human brain is the most complex and delicate of all the body’s organs, and the one most in need of protection from toxins and other harmful substances — including those we deliberately ingest. But to understand the effects drugs and disease have on the brain, scientists have needed to study how blood vessels, brain cells, and the blood-brain barrier (BBB) influence each other.
That’s been a challenge. In vitro models, like cells in a dish, have been too simple, and in vivo models — human brain tissue — too complex. Now, as reported in Nature Biotechnology, researchers at the Wyss Institute for Biologically Inspired Engineering have created a “just right” model of the BBB-brain interface using microfluidically linked organ chips that react to drugs like methamphetamine the same way the human brain does. The linked chips give researchers an unprecedented look into how the brain’s vasculature influences and regulates its metabolic function.
“We realized that the brain is already so complex that we couldn’t analyze it on one chip, so we did the opposite and divided one organ onto multiple chips,” said first author Ben Maoz, a former technology development fellow at the Wyss who is currently an assistant professor at Tel Aviv University. “Organ chips were able to open up another dimension for neurological research that no other method could, decoupling a very dense organ to unveil new interactions between the different structures within the brain.”
The BBB is comprised of blood vessels and a unique network of supporting pericyte and astrocyte cells. The blood vessels supply the brain with oxygen and nutrients, and they are highly selective about which molecules they allow to cross from the blood to the brain, and vice versa. When the BBB is disrupted, as it is when it is exposed to methamphetamine (“meth”) and other drugs, the brain’s sensitive neurons become susceptible to harmful damage. In addition, the BBB is thought to directly interact with the brain and help regulate its functions.