Surgery and anesthesia may contribute to cognitive impairment.

Anesthesia, a medical treatment that involves the use of anesthetic drugs, is a widely accepted strategy for managing pain during surgery. Evidence suggests that mice that have undergone surgery that involved anesthetic treatment exhibited signs of postoperative cognitive impairment. Findings from a 2017 study suggest that surgery in combination with the anesthetic drug isoflurane induces blood-brain barrier dysfunction, contributing to cognitive impairment.

Anesthetic drugs can be administered orally, intravenously, or via inhalation. Isoflurane is one of the most common inhaled anesthetics used in humans. Scientists don’t fully understand the mechanisms by which inhaled anesthetics work, but they appear to affect the central nervous system by depressing neurotransmission pathways. Previous research has shown that isoflurane increases several markers of inflammation.

The investigators wanted to determine whether the effects of surgery and anesthesia on blood-brain barrier permeability and cognitive function were related to age and/or the action of interleukin-6 (IL-6), a proinflammatory molecule. The experiment involved three types of mice: young female mice, old female mice, and young female mice that don’t carry the gene for IL-6. Previous research has shown that female mice are more vulnerable to the cognitive impairment associated with surgery and anesthesia. Half of the mice underwent a simple surgical procedure under anesthesia (isoflurane), while the remaining half did not. After the mice that had had surgery recovered, the investigators assessed all the animals' cognitive performance via a maze test, measured IL-6 in the animals' blood, and quantified proteins involved in maintaining blood-brain barrier integrity in the animals' brains.

They found that the mice that underwent anesthesia and surgery had greater blood-brain permeability and higher IL-6 levels than those that did not undergo the procedures. Notably, permeability increased as IL-6 levels and age increased. Levels of proteins involved in maintaining blood-brain barrier integrity were lower in the mice that underwent the procedure, and older mice were more likely to experience cognitive deficits after the procedures than younger mice.

These findings suggest that surgery with anesthesia induces cognitive decline in an age-dependent manner, and this decline may be due to inflammatory processes that drive blood-brain barrier dysfunction. Learn more about the blood-brain barrier in our new overview article.

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