C32-29 Cognitive Emergence From Anesthesia in Mice With Chronic Allergic Lung Inflammation

Rationale

Chronic lung inflammation increases pulmonary complications after general anesthesia, but its effects on anesthetic emergence and neurocognitive recovery remain poorly characterized. We previously observed altered neurocognitive behaviors in mice with chronic allergic lung inflammation. Since chronic peripheral inflammation can promote central nervous system (CNS) inflammation, we hypothesized that chronic allergic lung inflammation may selectively impair higher-order cognitive recovery after anesthesia without affecting basic arousal. We investigated whether chronic allergic lung inflammation alters recovery from general anesthesia in mice by measuring return of righting reflex (RORR, marker of emergence) and time to notice a sticky dot (marker of cognitive recovery).

Methods

In this IACUC-approved study, adult male and female wild-type C57BL/6J mice received daily intranasal house dust mite (HDM) antigen or PBS control for 6 weeks. Mice were anesthetized with inhaled isoflurane via nose cone (1.5% in 1L/min of 100% O2, 30 min) or propofol (20 mg/kg via tail vein injection), then monitored for RORR and time to notice of a sticky dot placed on the forepaw. Lung inflammation was confirmed by bronchoalveolar lavage (BAL) fluid cell count, BAL protein concentration, and lung histology.

Results

HDM-treated mice showed robust lung inflammation with increased perivascular and perialveolar mononuclear cell infiltrates and elevated BAL cell count and protein concentration compared to PBS controls. RORR times were nonsignificant between the HDM and PBS groups. However, following propofol anesthesia, HDM mice showed significantly delayed sticky dot response compared to PBS controls (HDM mean 446.5 sec ± 160.3, n = 21; PBS mean 353.9 ± 75.1, n = 21; p < 0.05, Welch’s t-test). Notably, sex-stratified analysis showed that the cognitive delay in HDM mice was driven primarily by females, with no statistically significant difference in males.

Conclusions

HDM-induced chronic allergic lung inflammation significantly delayed cognitive recovery in only female mice receiving propofol anesthesia, without altering basic arousal-related emergence. These findings suggest that chronic lung inflammation may preferentially impair higher-order cognition after exposure to certain types of anesthesia without necessarily prolonging emergence. The striking female predominance warrants investigation of sex-specific mechanisms and may have important clinical implications for under-recognized perioperative risk factors for delayed post-operative cognitive recovery in patients with asthma and related conditions.

This abstract is funded by: Louis V. Gerstner Jr. Scholars Program