Preoperative Sleep Deprivation Exacerbates Anesthesia/Surgery-induced Abnormal GABAergic Neurotransmission and Neuronal Damage in the Hippocampus in Aged Mice.

Abstract

Older adults with anesthesia and surgery often suffer from postoperative cognitive dysfunction (POCD), which puts a heavy burden on rehabilitation. Preoperative sleep disorder, a common phenomenon in elderly anesthesia patients, is closely associated with POCD, but the underlying mechanism is still not fully understood. Hippocampal gamma-aminobutyric acid (GABA)ergic neurotransmission has been reported to play an important role in sleep disorder and cognitive impairment. The aim of this study was to elucidate the effect of preoperative acute sleep deprivation (SD) on anesthesia/surgery-induced POCD and the potential mechanism of hippocampal GABAergic neurotransmission. In the aged (18-20-month-old) male mice, we used a rotating rod to deprive sleep for 24 h and induced a POCD model using sevoflurane exposure combined with laparotomy exploration. A sequential set of behavioral tests, including open field test (OFT), Y-maze, and novel object recognition (NOR), was conducted to assess cognitive performances. In vivo magnetic resonance imaging (MRI) technique was used to observe hippocampal axonal microstructural changes. The levels of GABAergic neurotransmitter markers glutamic acid decarboxylase (GAD) 67, vesicular GABA transporter (VGAT), GABA transporter (GAT)-1, and GABA in the hippocampus were detected with enzyme-linked immunosorbent assay (ELISA). The reactivity of GABAergic neurons and neuronal damage in different subregions of the hippocampus were observed by immunofluorescence and Nissl staining, respectively. Compared the anesthesia/surgery (A/S) mice, 24-h SD combined with A/S induced shorter stay time in the central area of the open field, less the percent of novel arm preference in the Y maze, and lower recognition index in the NOR, as well as significantly enhanced hippocampal GABAergic neurotransmission, decreased hippocampal axonal integrity and density, and increased GAD67 reactivity and reduced the number of neurons in hippocampal CA1. Preoperative 24-h SD exacerbated anesthesia/surgery-induced POCD in aged mice, with the cumulative effect of abnormal GABAergic neurotransmission and neuronal damage in the hippocampus.