Sevoflurane reduced functional connectivity of excitatory neurons in prefrontal cortex during working memory performance of aged rats.

BACKGROUND

Sevoflurane has been found to increase apoptosis and pathologic markers associated with Alzheimer disease, provoking concern over their potential contribution to postoperative cognitive dysfunction. This study aimed to evaluate the effects of sevoflurane on working memory of rats and to characterize functional connectivity between excitatory neurons in the prefrontal cortex (PFC) during working memory performance.

METHODS

18-month-old and 3-month-old male SD rats were implanted with a multielectrode array in the PFC. After recovery from the surgery, the aged and adult rats were divided into sevoflurane group and control group, respectively. Rats in sevoflurane group were exposed to 1 minimum alveolar concentration (MAC) or 1.5 MAC sevoflurane for two hours. At day1, 3, and 7 after exposure, the effects of sevoflurane anesthesia on working memory were investigated in the aged and adult rats by using delayed alternation in Y-maze. Spike trains of excitatory neurons in the PFC were recorded with the multielectrode array while rats were undergoing working memory performance. Functional connectivity between PFC excitatory neurons was described by Granger causal connectivity analysis.

RESULTS

In adult rats, 1.5 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons at day1 after exposure (P < 0.01). However, in aged rats, 1.5 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons at day1, 3, and 7 after exposure (P < 0.01). 1 MAC sevoflurane reduced working memory and functional connectivity between PFC excitatory neurons of aged rats at day1 after exposure (P < 0.01), but it had no effect in adult rats.

CONCLUSIONS

Sevoflurane-induced working memory impairment may depend on advanced age and anesthetic concentration. These findings also suggest, in rats, that sevoflurane-induced working memory impairment may be related to the decreased functional connectivity between PFC excitatory neurons.