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A Cleveland Clinic research team studying alcohol and the brain discovered a new way that alcohol abuse can cause brain dysfunction and damage: through immune cells called microglia. The research also identified a potential new treatment target.

The team showed that in a brain affected by alcohol, microglia tear down the extracellular matrix (ECM), the scaffold that surrounds our neurons. The ECM physically holds our brain cells together and allows them to work properly. When it's disrupted, our neurons can't communicate as effectively. Severe ECM disruption can affect our ability to move, think and even remain alert.

The research, published in Immunity, is new, fundamental knowledge that already guides the research team to explore new ways to prevent alcohol-related brain damage, says senior author Dimitrios Davalos, Ph.D.

Microglia are the brain's resident immune cells that monitor and respond to damage and abnormalities in our brains, often acting as vacuum cleaners sucking up and cleaning out debris. Microglia also prune neuronal connections as part of healthy brain development.

Each microglial cell is constantly surveying our brain with its many branch-like processes. Davalos' team used advanced imaging techniques to follow the same microglia over time, before and after repeated exposure to alcohol. They made several discoveries:

This study benefited from long-standing expertise at the Northern Ohio Alcohol Center. Cleveland Clinic's Pathology and Laboratory Medicine Institute also provided frontal cortex samples from people with alcohol use disorder, where the team identified the same ECM disruption, the first direct evidence that this scaffold is also dismantled in the human brain.

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