Reduction of Orexin‐A is Responsible for Prolonged Emergence of the Rat Subjected to Sleep Deprivation from Isoflurane Anesthesia

Abstract

Sleep deprivation (SD) especially insomnia is commonly encountered in clinic. Many factors can cause insomnia, such as anxiety, fear, pain, medication, and disruptive environment [1]. Sleep disorder during the perioperative period may cause a number of complications, including delayed anesthesia emergence. However, the mechanism underlying this phenomenon remains elusive.It has been postulated that common neural pathways between natural sleep and general anesthesia may be involved in the regulation of anesthesia emergence times [2]. Orexin is a peptide that consists of orexin-A (OXA) and orexin-B (OXB) subtypes [3]. Accumulated evidence suggests that orexinergic neurons play a critical role in the promotion and maintenance of wakefulness [4]. It has been reported that orexinergic neurons participate in the control of rapid eye movement (REM) sleep and the orexin-1 receptor is particularly necessary in the suppression of REM sleep [5]. Our earlier studies demonstrated that activation of the orexinergic signals in the basal forebrain significantly increased acetylcholine efflux in the somatosensory cortical region and shortened the awakening time of rats under inhalation or intravenous anesthesia [6]. These findings strongly supported the notion that orexinergic neurons might play a crucial role in the regulation of postanesthesia arousal.It has been reported that the anesthesia behaviors of rats change after SD in terms of time of reduced loss of righting reflex (LORR) and delayed recovery of the righting reflex (RORR) [7]. These alterations strongly suggest that sleep pattern changes might modulate the effectiveness of general anesthetics. Furthermore, administration of adenosine A1 and A2 receptor antagonists partially reversed the effect of SD, but the awakening time did not return to its original length [8]. We hypothesize that the delayed emergence from general anesthesia after SD is associated with the orexinergic neural pathway and experimentally verified the hypothesis in the rat.To determine whether the delayed emergence from anesthesia after SD is due to the alteration of the orexinergic neuron's activity, the animals were divided into two groups: SD group and sham-SD group. We adopted a modified multiple-platform method to deprive REM sleep of the rats in SD group for 24 h. The plasma OXA concentrations were measured by radioimmunoassay (RIA) after SD. Results showed that the plasmic concentration of OXA in the sham-SD group was 25.2 AE 2.43 pg/mL, but decreased to 17.8 AE 1.29 pg/mL at 24 h after sleep deprivation.Next, we recorded both induction and emergence time in the two groups of rats subjected to isoflurane anesthesia. We found that the SD had no effects on the induction time, but increased the duration of emergence in isoflurane anesthesia. The induction time of the SD group (1.90 AE 0.12 min) was similar to that of the sham-SD group (1.83 AE 0.09 min, P < 0.05). However, the emergence time in the SD rats (16.9 AE 0.63 min) was significantly longer than that of the sham-SD group (14.8 AE 0.42 m...

RNA-seq expression profiling of rat MCAO model following reperfusion Orexin-A

“…Orexin-A is a novel neuropeptide involved in the regulation of feeding behaviour [ 1 , 2 ], energy metabolism [ 3 ], hormone secretion [ 4 ], the sleep-wake cycle [ 5 ] and anaesthesia [ 6 ]. Orexin-A plays a pivotal role in neurotrauma [ 7 ], Parkinson's disease [ 8 ], narcolepsy [ 9 ], vascular diseases [ 10 ] and brain tumours [ 11 , 12 ].…”

The Inert Brain: Explaining Neural Inertia as Post-anaesthetic Sleep Inertia

“…Moreover, orexin is known to be involved in anaesthetic action: the activity of orexin neurons is reduced by propofol, sevoflurane and isoflurane, as indicated by a reduced number of c-Fos-immuno-reactive orexinergic neurons in rodents ( Kelz et al, 2008 ; Zhang et al, 2012 ; Scharf and Kelz, 2013 ). Moreover, rodent studies show that reduced activation of orexin neurons during anaesthesia is exacerbated when the anaesthesia is administered under conditions of sleep deprivation ( Ran et al, 2015 ). Conversely, intracerebroventricular administration of orexin-A (though not orexin-B) causes emergence from propofol, isoflurane and sevoflurane anaesthesia in rats ( Dong et al, 2009 ; Shirasaka et al, 2011 ; Zhang et al, 2012 , 2016 ), and similar results have also been obtained in mice, whereby activation of orexin neurons with DREADDs facilitated emergence from isoflurane anaesthesia ( Zhou et al, 2018 ).…”

Increased minimum alveolar concentration-awake of Sevoflurane in women of breast surgery with sleep disorders

“…Patients with sleep disorders are more likely to experience postoperative complication like delirium [1,2]. It has been shown that sleep deprivation can modulate the effectiveness of general anesthetics in rats, including hypersensitivity to induction of anesthesia, or delayed emergence from anesthesia [ 3,4]. However, the mechanism of sleep changes affect general anesthesia remains unclear.…”