The Impact of Inflammation and General Anesthesia on Memory and Executive Function in Mice

Abstract

Cognition After Inflammation and Anesthesia P < .001; cortex: 2.60 pg/mg [0.83-4.40], P = .010) and tumor necrosis factor-α (hippocampus: 3.50 pg/mg [0.83-11.82], P = .002; cortex: 2.38 pg/mg [0.44-4.31], P = .021). Recognition memory was impaired in mice treated with LPS, as evinced by a lack of preference for the novel object (novel versus familiar: 1.03 seconds [−1.25 to 3.30], P = .689), but not in mice treated with etomidate alone (novel versus familiar: 2.38 seconds [0.15-4.60], P = .031). Mice cotreated with both LPS and etomidate also exhibited memory deficits (novel versus familiar: 1.40 seconds [−0.83 to 3.62], P = .383). In the puzzle box, mice treated with either LPS or etomidate alone showed no deficits. However, the combination of LPS and etomidate caused deficits in problem-solving tasks (door open task: −0.21 seconds [−0.40 to −0.01], P = .037; plug task: −0.30 seconds [−0.50 to −0.10], P < .001; log values versus control), indicating impaired executive function. CONCLUSIONS: Impairments in recognition memory were driven by inflammation. Deficits in executive function were only observed in mice cotreated with LPS and etomidate. Thus, an interplay between inflammation and etomidate anesthesia led to cognitive deficits that were not observed with either factor alone. These findings suggest that inflammation and anesthetic drugs may interact synergistically, or their combination may unmask covert or latent deficits induced by each factor alone, leading to PNDs.

The Preventive Effect of Urinary Trypsin Inhibitor on Postoperative Cognitive Dysfunction, on the Aspect of Behavior, Evaluated by Y-Maze Test, via Modulation of Microglial Activity

“…This could misrepresent the idea that general anesthesia has a detrimental effect on cognitive function, although the effect of general anesthesia on cognitive function is controversial and complex. Several studies have shown that short- and long-term effects of general anesthesia on cognitive function differ [ 34 , 35 ]. Some studies have shown positive effects of general anesthesia on cognitive function [ 36 ].…”

Discovering the Intriguing Properties of Extrasynaptic γ-Aminobutyric Acid Type A Receptors

“…The study reported in the PNAS article laid the foundation for subsequent experiments in which we, along with other researchers, demonstrated the heightened sensitivity of these receptors to anesthetic drugs and their role in neuroplasticity and cognitive processes. [2][3][4][5][6][7][8][9][10][11][12][13][14] The PNAS report represented a turning point in my research career. These enigmatic receptors have since captured my laboratory's attention as potential therapeutic Beverley A.…”

“…Although some patients experience insufficient memory loss and have intraoperative awareness, 36 others unexpectedly develop persistent postoperative memory deficits, which might contribute to postoperative cognitive disorders. 3,[37][38][39] Also, by understanding how anesthetic drugs impair memory, we might gain insights into the cause of memory deficits associated with conditions like traumatic brain injury 4 and Alzheimer disease. 40,41 We started by searching for synaptic GABA A receptors that were modified by low, amnestic concentrations of propofol and the classic benzodiazepine midazolam.…”

“…The study reported in the PNAS article laid the foundation for subsequent experiments in which we, along with other researchers, demonstrated the heightened sensitivity of these receptors to anesthetic drugs and their role in neuroplasticity and cognitive processes. 2–14…”

Reduced excitatory neurotransmission in the hippocampus after inflammation and sevoflurane anaesthesia

“… 5 , 6 To study the multifactorial aetiology of PNDs, rodent models combining these two factors have been recently developed. 7 , 8 In these aseptic, non-surgical models, inflammation is induced by injection of the endotoxin lipopolysaccharide (LPS); the rodents are then treated with either an injectable or an inhaled general anaesthetic drug. We and others have observed cognitive deficits in adult and immature animals treated with the combination of LPS and an anaesthetic drug that were not observed after treatment with either factor alone.…”