New scientific model reveals interaction between blood vessels and neurons in the brain

Micro-flow models of the blood-brain barrier and the brain reveal for the first time complex metabolic interactions between the brain’s blood vessels and nerve cells. The findings are published by an international team of researchers, including from Karolinska Institutet and the Royal Institute of Technology, in the journal Nature Biotechnology.

Interaction and regulation between blood vessels and nerve cells in the brain are essential to its function, but how this interaction takes place has been difficult to pin down. Classic cell-culture models of nerve cells and blood vessel cells are too simplified to show interactions, and studies on brain tissue and animals are too complicated.

In order to understand how blood vessels and surrounding brain tissue interact, the team built up a so-called “organ-on-chip”-model, which is a micro-flow model with living cells.

Using the model, the researchers were able to analyse all the smaller molecules issued by the cells and identify a previously undescribed link for how blood vessel cells metabolise glucose and how these metabolites influence the production of neurotransmitters by the neurons.

The team is now working on using these systems to obtain new insights on the brain and to build models of brain diseases.

The study was financed by the Wyss Institute for Biologically Inspired Engineering at Harvard University, Defense Advanced Research Projects Agency (DARPA), the Sweden-America Foundation, the Carl Trygger Foundation and the Erik and Edith Fernström Foundation.

Publication

“A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells”
Ben M Maoz, Anna Herland, Edward A FitzGerald, Thomas Grevesse, Charles Vidoudez, Alan R Pacheco, Sean P Sheehy, Tae-Eun Park, Stephanie Dauth, Robert Mannix, Nikita Budnik, Kevin Shores, Alexander Cho, Janna C Nawroth, Daniel Segrè, Bogdan Budnik, Donald E Ingber and Kevin Kit Parker
Nature Biotechnology, online 20 August 2018, doi: 10.1038/nbt.4226