Researchers at the Institute of Science and Technology Austria have found that immune cells in the brain, known as microglia, play a critical role in the recovery process from ketamine anesthesia, with notable differences between female and male brains. The findings were published in Science Advances, according to a Jul. 31 announcement.
The study used cranial windows and fluorescent markers to observe how microglia and neurons behave during recovery from ketamine anesthesia in mice. The researchers discovered that as female mice recovered, microglia formed prolonged contacts with neurons coinciding with synaptic remodeling and plasticity. This phenomenon was not observed in male mice or in those lacking microglia.
"What was fascinating," Alessandro Venturino said, "was that we observed this plasticity—the brain's ability to change, adapt, and in this case recover—only in females." Professor Sandra Siegert added, "I've always believed that women have greater brain plasticity. Alessandro and I just couldn't let it go—we wanted to know why."
Further experiments revealed that this plasticity depends on corticosterone, a major stress hormone. Venturino said, "During recovery from anesthesia, corticosterone levels rise. In female mice, this specifically activates the stress‑response gene Fkbp5 in microglia... apparently prompts microglia to interact with neurons." Removal of adrenal glands eliminated these effects during recovery.
Siegert noted, "They also remind us that stress is not always harmful—stress hormones are essential for certain processes in the brain." She speculated about evolutionary reasons for greater adaptability among females but cautioned about potential risks: "But if this plasticity becomes too frequent or too intense, it can increase the risk of depression... psychiatric disorders are more prevalent in women than men." Siegert also pointed out limited prior research on sex-specific responses to ketamine.
"It's astonishing how readily people assume that men and women respond to drugs in the same way—when clearly they do not," Siegert said. The researchers emphasized the importance of considering sex-specific differences when studying medications like ketamine.
