Yokukansan suppresses neuroinflammation in the hippocampus of mice and decreases the duration of lipopolysaccharide- and diazepam-mediated loss of righting reflex induced by pentobarbital.

Neuroinflammation is associated with the development of hypoactive delirium, which results in poor clinical outcomes. Drugs effective against hypoactive sur have not yet been established. Yokukansan has an anti-neuroinflammatory effect, making it potentially effective against hypoactive delirium. This study aimed to examine the effect of Yokukansan on the pentobarbital-induced loss of righting reflex duration extended with lipopolysaccharide (LPS)-induced neuroinflammation and diazepam-induced gamma-aminobutyric acid receptor stimulation in a mouse model. The active ingredients in Yokukansan and its anti-neuroinflammatory effect on the hippocampus were also investigated. Furthermore, we examined the in vitro anti-inflammatory effects of Yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Findings revealed that treatment with Yokukansan significantly decreased the duration of pentobarbital-induced loss of righting reflex by attenuating the LPS-induced increase in interleukin-6 and tumor necrosis factor-alpha levels in the hippocampus. Moreover, treatment with Yokukansan significantly decreased the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus after 24 h of LPS administration. In addition, glycyrrhizic acid, an active ingredient in Yokukansan, partially decreased the duration of pentobarbital-induced loss of righting reflex. Treatment with Yokukansan also suppressed the expression of inducible nitric oxide, interleukin-6, and tumor necrosis factor mRNA in LPS-stimulated BV2 cells. Thus, these findings suggest that Yokukansan and glycyrrhizic acid may be effective therapeutic agents for treating neuroinflammation-induced hypoactive delirium.

Post-operative delirium associated with metabolic alterations following hemi-arthroplasty in older patients.

BACKGROUND: post-operative delirium (POD) is a common complication in older patients, though a possible link between metabolic changes and POD development has yet to be investigated. METHODS: older patients with hip fracture who underwent hemi-arthroplasty were recruited, and delirious states were assessed for 3 days after surgery using the confusion assessment method-Chinese revision. Simultaneously, fasting blood samples were collected on the morning of surgery and on the first post-operative day. Ultimately, 244 older patients who met the inclusion and exclusion criteria were assessed. Blood samples from 60 patients with POD and 60 matched controls were analysed using metabolomics platforms. RESULTS: sixty patients (24.6%) developed POD. Principal component analysis scores plot and cross-validated scores plots from orthogonal partial least squares-discriminant analysis were implemented to visualise the differences in metabolites between the two groups before and after surgery (P < 0.05). Our data indicate that levels of ω3 and ω6 fatty acids were lower in the POD group than in the NPOD (non-POD) group both before and after surgery; tricarboxylic cycle intermediate levels were lower in the POD group than in the NPOD group, but glycolysis products were higher in the POD group than in the NPOD group after surgery. Furthermore, the branched-chain amino acid (BCAA)/aromatic amino acid ratio was lower in the POD group than in the NPOD group after surgery. CONCLUSIONS: metabolic abnormalities, including deficiencies in ω3 and ω6 fatty acids, perturbations in tricarboxylic cycle and oxidative stress and metabolic imbalances in BCAA and AAA might contribute to POD development.

Effects of nimodipine on postoperative delirium in elderly under general anesthesia: A prospective, randomized, controlled clinical trial.

Nimodipine is a clinical commonly used calcium antagonistscan lowering the apoptosis rate of hippocampal neuron to reduce the incidence of postoperative cognitive dysfunction (POCD). This study was designed to evaluate the effects of nimodipine on postoperative delirium in elderly under general anesthesia.Sixty patients shceduced spine surgery under general anesthesia were randomly assigned into 2 groups using a random number table: control group (Group C) and nimodipine group (Group N). In Group N, nimodipine 7.5 µg/(kg × h) was injected continually 30 minutes before anesthesia induction, while the equal volume of normal saline was given in Group C. At 0 minute before injection, 0 minute after tracheal intubation, 1 hour after skin incision and surgery completed (T1-4), blood samples were taken from the radial artery and jugular bulb for blood gas analysis. Cerebral oxygen metabolism-related indicators were calculated at the same time. Concentration of S100ß and glial fibrillary acidic protein (GFAP) were tested by ELISA. The incidence of postoperative delirium within 7 days after surgery was recorded.Cerebral oxygen metabolism-related indicators fluctuationed in the normal range in 2 groups at different time points and the difference were not statistically significant. Compared with Group C, S100ß and GFAP decreased and incidence of postoperative delirium reduced at T3-4 in Group N, the difference was statistically significant (P<.05).The present study suggests that nimodipine can reduce the development of postoperative delirium in elderly patients under general anesthesia, the reduction of brain injury and improvement of cerebral oxygen metabolism may be involved in the mechanism.