Scientists at the University of Rochester are using innovative brain-on-a-chip technology to better understand how the brain protects itself and how this process goes wrong in diseases such as sepsis and neurodegenerative disorders. Instead of animal testing, the researchers are using microchips with human tissue, which allow them to study what happens at the blood-brain barrier: the crucial boundary between the bloodstream and the brain.
When a patient undergoes major surgery or contracts an infection such as sepsis, the immune system can react so violently that organs, including the brain, become inflamed. This often leads to long-term cognitive problems, especially in the elderly.
Brain damage due to inflammation
In a study published in Advanced Science, Professor James McGrath's team demonstrated how a so-called cytokine storm affects the blood-brain barrier. Using tissue chips, the researchers observed that an excessive immune response breaks down the membrane between the blood and the brain, allowing harmful proteins to enter the brain and cause damage.
‘Blood proteins such as fibrinogen, in combination with inflammatory factors, can trigger harmful changes in the brain's support cells,’ explains PhD student Kaihua Chen. ‘Interestingly, we discovered that natural blood flow actually plays a protective role and helps to keep the barrier strong. This shows how biology and engineering can work together to provide new insights into how the brain defends itself.’
Microglia cells
The researchers want to further expand the chip with microglia cells, the brain's immune cells, to better understand how neurons are damaged during inflammation. Ultimately, the technology should contribute to the development of drugs that can prevent brain damage in sepsis.
McGrath also sees applications in personalised medicine: ‘With a personalised brain chip, we can predict how a specific patient's brain will respond to heavy treatments such as chemotherapy or surgery, and thus adjust the medication and dosage to prevent brain damage.’
New insights into brain protection
In a second study, published in Materials Today Bio, the team focused on pericytes. These are support cells that are essential for the stability of the blood-brain barrier, but often disappear in neurodegenerative diseases. By creating small openings in blood vessel tissue, the researchers discovered that pericytes repair these defects by forming a network of structural fibres, allowing the barrier to recover.
‘The loss of pericytes plays a role in many brain disorders,’ says PhD student Michelle Trempel. ‘With this chip, we can finally investigate exactly how that loss contributes to neurodegeneration and how we might be able to counteract it.’ Rochester's brain-on-a-chip technology brings researchers one step closer to safely and accurately modelling brain disorders without animal testing, and opens new avenues for smarter, patient-specific treatments for inflammatory and neurodegenerative damage.
Last year, we reported on successful Dutch brain-on-a-chip research that demonstrated that the treatment of Dravet syndrome, a rare congenital form of epilepsy, can be improved with this technology.
