Cognitive Decline After Surgery Tied to Brain's Own Immune Cells

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After undergoing surgery, elderly patients often experience cloudy thinking that can last for weeks or even months. At one time researchers thought this cognitive decline might be caused by anesthesia, but mounting evidence suggests that heightened inflammation in the brain following surgery is the more likely cause.

Now a new study in mice by UC San Francisco researchers suggests that brain inflammation and cognitive decline following surgery are triggered by the brain’s own specialized immune cells, called microglia. Mice given an experimental oral drug that temporarily depletes microglia ahead of an operation were much less likely to fail memory tests several days after surgery, the UCSF team found, suggesting a possible new approach to preventing the condition in humans.

The study, published April 6 in JCI Insight, an online, open-access companion publication to the Journal of Clinical Investigation, was led by collaborators Suneil Koliwad, MD, PhD, assistant professor of medicine, and Mervyn Maze, MD, professor of anesthesia and perioperative care at UCSF. Koliwad has been studying microglia for several years, and Maze developed the mouse model that was used to investigate cognitive effects of surgery. “There is an impact on memory in the mouse model that mirrors what has been observed in studies of post-surgical cognitive impairment in humans, and we can mitigate it with treatment that we think is not harmful to the animal,” said Koliwad, who holds the Gerold Grodsky, PhD/JAB Chair in Diabetes Research at the UCSF Diabetes Center. “When we depleted microglia before surgery, the mice remembered much better after surgery in comparison to mice that did not receive the drug. Furthermore, we found much lower levels of inflammatory molecules in the hippocampus, a brain region that plays a key role in memory.” Excess Inflammation May Trigger Cognitive Decline After Surgery Surgeries in elderly patients are becoming more common, and cognitive impairment is increasingly acknowledged ...

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