Creating a “microbrain bioreactor” is the challenge of a new $2.1 million research grant awarded to an interdisciplinary team of researchers. The entire device will be about the size of a grain of rice.

Take a millionth of a human brain and squeeze it into a special chamber the size of a mustard seed. Link it to a second chamber filled with cerebral spinal fluid and thread both of them with artificial blood vessels in order to create a microenvironment that makes the neurons and other brain cells behave as if they were in a living brain. Then surround the chambers with a battery of sensors that monitor how the cells respond when exposed to minute quantities of dietary toxins, disease organisms or new drugs under development.

Creating such a “microbrain bioreactor” is the challenge of a new $2.1 million research grant awarded to an interdisciplinary team of researchers from Vanderbilt University, Vanderbilt University Medical Center, the Cleveland Clinic and Meharry Medical College. The grant is one of 17 that are being issued by the National Center for Advancing Translational Sciences at the National Institutes of Health as part of a $70 million “Tissue Chip for Drug Testing” program. The five-year program is a cooperative effort on the part of NIH, the Defense Advanced Research Projects Agency and the FDA.

The reason for microfabricating organ simulators containing small populations of human cells – generally known as organ-on-a-chip technology – is to bridge the formidable gaps that exist between the tools that researchers currently use to develop new drugs – cell cultures and animal and human testing. These gaps not only add substantially to the difficulty and expense of developing new drugs but also contribute to the large number of experimental drugs that aren’t effective or have unacceptable side effects when they are finally tested on people.

The brain is a particularly difficult target for drug development because it is surrounded by three barriers that protect it from molecular or cellular intruders. The most formidable of these is the blood-brain barrier (BBB). It surrounds the blood vessels that service the brain and allows the passage of compounds that the brain needs while simultaneously blocking the passage of other types of molecules, both foreign and domestic. The two other barriers protect the neurons from contaminants in the cerebral spinal fluid and protect the cerebral spinal fluid from contaminants in the blood. Not only do these barriers block potentially harmful molecules, neuroscientists have also discovered that they occasionally alter the chemistry of some of the compounds that they let through.

“Given the differences in cellular biology in the brains of rodents and humans, development of a brain model that contains neurons and all three barriers between blood, brain and cerebral spinal fluid, using entirely human cells, will represent a fundamental advance in and of itself,” said John Wikswo, director of the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE), who is orchestrating the multidisciplinary effort.

Wikswo and his collaborators argue that this new type of brain model should provide new insights into how the brain receives, modifies and is affected by drugs and disease agents. By replicating the forms of chemical communication and molecular trafficking that take place in the human brain, the device will allow them to test the effectiveness of various drug and nutritional therapies designed to prevent both acute injuries like strokes and chronic diseases like obesity and epilepsy, as well as uncovering the potential adverse effects of experimental drugs.

By David Salisbury. For the full article, with details of collaborating groups, see: http://news.vanderbilt.edu/2012/07/microbrain/?goback=.gde_3287601_member_138128873

Image: Artist’s conception of the microbrain bioreactor. The upper chamber contains the neurons and an artificial capillary that carries blood to the brain surrounded by the cells that make up the blood-brain barrier. The lower layer is filled with cerebral spinal fluid (CSF) and contains an artificial choroid plexus (red) that makes CSF and a venule (blue) that carries blood away from the brain, along with a collection of cells that form the blood-CSF and CSF-brain barriers. Collectively, all these cells will reproduce the microenvironment found in the brain. The entire device will be about the size of a grain of rice. (Dominic Doyle and Frank Block / Vanderbilt)