Isoflurane-Induced Spatial Memory Impairment in Mice is Prevented by the Acetylcholinesterase Inhibitor Donepezil

Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane

A bibliometric analysis of preoperative anxiety research (2001–2021)

Recently, mental health has received increasing attention, particularly preoperative anxiety, which constitutes a bad emotional experience for surgical patients. Many experts have studied preoperative anxiety in terms of its related risk factors, interventions, and postoperative effects; however, there has been no systematic analysis of published articles. This paper presents a bibliometric review of documents related to preoperative anxiety published between 2001 and 2021. A detailed data analysis of 1,596 publications was conducted using CiteSpace and VOSviewer. Since the 20th century, the field of preoperative anxiety has gradually developed; research began around 2000 and has made a huge leap forward since 2016. Developed countries, led by the United States, were the first to conduct research, but preoperative anxiety research in developing countries like Turkey and China has gradually increased and led to an irreplaceable contribution. Intervention has remained the main topic of preoperative anxiety research, and measures have developed from premedication to the provision of education and information. Moreover, the use of advanced equipment such as virtual reality has emerged with great popularity. Based on previous research, the application of virtual reality combined with pediatric patients will become a new research direction

Neuroinflammation Induced by Surgery Does Not Impair the Reference Memory of Young Adult Mice

Postoperative cognitive dysfunction (POCD) increases morbidity and mortality after surgery. But the underlying mechanism is not clear yet. While age is now accepted as the top one risk factor for POCD, results from studies investigating postoperative cognitive functions in adults have been controversial, and data about the very young adult individuals are lacking. The present study investigated the spatial reference memory, IL-1 , IL-6, and microglia activation changes in the hippocampus in 2-month-old mice after anesthesia and surgery. We found that hippocampal IL-1 and IL-6 increased at 6 hours after surgery. Microglia were profoundly activated in the hippocampus 6 to 24 hours after surgery. However, no significant behavior changes were found in these mice. These results indicate that although anesthesia and surgery led to neuroinflammation, the latter was insufficient to impair the spatial reference memory of young adult mice

Neuroinflammation Induced by Surgery Does Not Impair the Reference Memory of Young Adult Mice

Postoperative cognitive dysfunction (POCD) increases morbidity and mortality after surgery. But the underlying mechanism is not clear yet. While age is now accepted as the top one risk factor for POCD, results from studies investigating postoperative cognitive functions in adults have been controversial, and data about the very young adult individuals are lacking. The present study investigated the spatial reference memory, IL-1β, IL-6, and microglia activation changes in the hippocampus in 2-month-old mice after anesthesia and surgery. We found that hippocampal IL-1β and IL-6 increased at 6 hours after surgery. Microglia were profoundly activated in the hippocampus 6 to 24 hours after surgery. However, no significant behavior changes were found in these mice. These results indicate that although anesthesia and surgery led to neuroinflammation, the latter was insufficient to impair the spatial reference memory of young adult mice

Pre-operative administration of butorphanol mitigates emergence agitation in patients undergoing functional endoscopic sinus surgery: A randomized controlled clinical trial

BackgroundThis study explored the effectiveness of pre-operative intravenous injection of butorphanol in the alleviation of emergence agitation (EA) in patients undergoing functional endoscopic sinus surgery (FESS).MethodsPatients (n = 708) were randomized into two groups. The butorphanol group (Group B, n = 358) received butorphanol infusion (20 ug/kg) before anesthesia induction, while the control group (Group C, n = 350) received an equal volume of normal saline infusion. General anesthesia was induced with sufentanil, propofol, and rocuronium, and was maintained with sevoflurane and remifentanil. Vasoactive drugs maintained the hemodynamic indices within 20% of the baseline.ResultsThe incidence of EA was significantly lower in Group B than that in Group C (Group B vs. C: 24.3% vs. 31.4%, respectively; P = 0.034). The times to spontaneous breathing (26.5 min vs. 23.7 min, P = 0.011), verbal response (36.0 min vs. 33.4 min, P = 0.012), and extubation (31.0 min vs. 28.7 min, P = 0.025) were longer in Group B, and the grade of cough (0.33 vs. 0.43, P = 0.024) at extubation in Group B was lower than that in Group C (P = 0.024). The mean arterial pressure at the end of the operation (P = 0.004) and at 5 min after extubation (P = 0.008) was higher and hypotension was less prominent (0.6% vs. 2.6%, P = 0.030) in Group B.ConclusionPre-operative intravenous injection of butorphanol decreased the incidence of EA after FESS and provided smooth and hemodynamically stable emergence without extending the stay in post-anesthesia care unit.Clinical trial registrationhttps://www.clinicaltrials.gov/, identifier NCT03398759

Intrathecal Injection of Spironolactone Attenuates Radicular Pain by Inhibition of Spinal Microglia Activation in a Rat Model

Microglia might play an important role in nociceptive processing and hyperalgesia by neuroinflammatory process. Mineralocorticoid receptor (MR) expressed on microglia might play a central role in the modulation of microglia activity. However the roles of microglia and MR in radicular pain were not well understood. This study sought to investigate whether selective MR antagonist spironolactone develop antinociceptive effects on radicular pain by inhibition neuroinflammation induced by spinal microglia activation.Radicular pain was produced by chronic compression of the dorsal root ganglia with SURGIFLO™. The expression of microglia, interleukin beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), NR1 subunit of the NMDA receptor (t-NR1), and NR1 subunit phosphorylated at Ser896 (p-NR1) were also markedly up-regulated. Intrathecal injection of spironolactone significantly attenuated pain behaviors as well as the expression of microglia, IL-1β, TNF-α, t-NR1, and p-NR1, whereas the production of IL-6 wasn't affected.These results suggest that intrathecal delivery spironolactone has therapeutic effects on radicular pain in rats. Decreasing the activation of glial cells, the production of proinflammatory cytokines and down-regulating the expression and phosphorylation of NMDA receptors in the spinal dorsal horn and dorsal root ganglia are the main mechanisms contributing to its beneficial effects

Postoperative cognitive dysfunction after robot-assisted radical cystectomy (RARC) with cerebral oxygen monitoring an observational prospective cohort pilot study

Abstract Background The incidence and risk factors of postoperative cognitive dysfunction (POCD) during robot-assisted radical cystectomy (RARC) in extreme Trendelenburg positioning and pneumoperitoneum are still controversial. The aim of this prospective observational study was to find the incidence rate as well as possible risk factors of POCD in RARC with cerebral oxygen monitoring. Methods Patients who underwent RARC and open abdominal surgery in horizontal positioning were included. Preoperative and postoperative arterial blood gas (ABG), S-100β, C-reactive protein (CRP), and cognitive dysfunction scales were tested. Also, we used Z score to analyze and comprehensively evaluate POCD. Measurements of heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), end-tidal CO2 (etCO2), and cerebral oxygen were immediately obtained after different time points during the surgery. Results Here, 24 and 23 patients were included in the RARC group and in the control group, respectively. The incidence of POCD didn’t have significant difference in RARC group (45.8%), in contrast to the control group (26.1%). The laboratory tests of s100β and CRP between two groups didn’t contain significant difference as well. As duration of Trendelenburg and pneumoperitoneum prolonged, the cerebral oxygen saturation in the RARC group increased, which didn’t cause excessive perfusion nevertheless (rSO2&lt;75%). We compared laboratory tests, age, education status, blood loss, and fluid input between POCD and non-POCD patients. A significant difference was found in the serum concentrations of CRP (72.59 ± 42.09 vs. 48.50 ± 26.53, P = 0.025) and age (69.20 ± 7.033 vs. 65.34 ± 5.228, P = 0.041). Conclusion RARC in extreme Trendelenburg positioning and pneumoperitoneum did not significantly increase the incidence of POCD and didn’t cause excessive perfusion. The inflammation marker CRP and age might be independent risk factors of POCD. Trial registration Clinicaltrials.gov with registration number NCT03372135. Registered 1 November 2017 (retrospectively registered). </jats:sec