Effects of adding adjuvants to propofol on the post-anesthesia cognitive function in patients undergoing gastroscopy/colonoscopy: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to elucidate the effects of propofol plus adjuvants on postoperative cognitive dysfunction (POCD) and patient satisfaction. METHODS: Studies published up to September 2023 on the Chinese National Knowledge Infrastructure (CNKI), Wanfang Data, Sinomed, PubMed, Embase, Cochrane Library, Web of Science, and Clinictrials.gov websites were searched. Binary summary of results was used for meta-analyses. RESULTS: We included 18 studies (2691 patients). The combined sedation did not affect the processing speed (ES = 0.02, 95%CI: -0.01, 0.04; I2 = 79.3%, p < 0.001), attention (ES = 0.02, 95%CI: -0.02, 0.05; I2 = 95.0%, p < 0.001), nor working memory (ES = 0.02, 95%CI: -0.03, 0.06; I2 = 94.4%, p < 0.001) in CogState brief battery tool. A significant effect of combined sedation was observed in the domain of visual learning in CogState tool (ES = -0.03, 95%CI: -0.04, -0.02; I2 = 15.8%, p = 0.306). The TDT (ES = 4.96, 95%CI: 2.92, 7.00) indicates that combined sedation would increase error rates in the tests of cognitive function. The DSST (ES = 0.16, 95% CI: -0.44, 0.75) shown that combined sedation does not affect cognitive function. In addition, an insignificant difference in patient satisfaction between combined sedation and propofol alone was observed (ES = -0.03, 95%CI: -0.09, 0.02). CONCLUSION: The available evidence suggests that propofol combined with adjuvants may affect POCD but not patient satisfaction. REGISTRATION NUMBER: INPLASY2023110092.

Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula.

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation.

Adenosine A2A receptor controls the gateway of the choroid plexus.

The choroid plexus (CP) is one of the key gateways regulating the entry of peripheral immune cells into the CNS. However, the neuromodulatory mechanisms of maintaining its gateway activity are not fully understood. Here, we identified adenosine A2A receptor (A2AR) activity as a regulatory signal for the activity of CP gateway under physiological conditions. In association with a tightly closed CP gateway, we found that A2AR was present at low density in the CP. The RNA-seq analysis revealed that the A2AR antagonist KW6002 affected the expression of the cell adhesion molecules' (CAMs) pathway and cell response to IFN-γ in the CP. Furthermore, blocking or activating A2AR signaling in the CP resulted in a decreased and an increased, respectively, expression of lymphocyte trafficking determinants and disruption of the tight junctions (TJs). Furthermore, A2AR signaling regulates the CP permeability. Thus, A2AR activity in the CP may serve as a therapeutic target for remodeling the immune homeostasis in the CNS with implications for the treatment of neuroimmunological disorders.

Choroid plexus-selective inactivation of adenosine A2A receptors protects against T cell infiltration and experimental autoimmune encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is one of the most common autoimmune disorders characterized by the infiltration of immune cells into the brain and demyelination. The unwanted immunosuppressive side effect of therapeutically successful natalizumab led us to focus on the choroid plexus (CP), a key site for the first wave of immune cell infiltration in experimental autoimmune encephalomyelitis (EAE), for the control of immune cells trafficking. Adenosine A2A receptor (A2AR) is emerging as a potential pharmacological target to control EAE pathogenesis. However, the cellular basis for the A2AR-mediated protection remains undetermined. METHODS: In the EAE model, we assessed A2AR expression and leukocyte trafficking determinants in the CP by immunohistochemistry and qPCR analyses. We determined the effect of the A2AR antagonist KW6002 treatment at days 8-12 or 8-14 post-immunization on T cell infiltration across the CP and EAE pathology. We determined the critical role of the CP-A2AR on T cell infiltration and EAE pathology by focal knock-down of CP-A2AR via intracerebroventricular injection of CRE-TAT recombinase into the A2ARflox/flox mice. In the cultured CP epithelium, we also evaluated the effect of overexpression of A2ARs or the A2AR agonist CGS21680 treatment on the CP permeability and lymphocytes migration. RESULTS: We found the specific upregulation of A2AR in the CP associated with enhanced CP gateway activity peaked at day 12 post-immunization in EAE mice. Furthermore, the KW6002 treatment at days 8-12 or 8-14 post-immunization reduced T cell trafficking across the CP and attenuated EAE pathology. Importantly, focal CP-A2AR knock-down attenuated the pathogenic infiltration of Th17+ cells across the CP via inhibiting the CCR6-CCL20 axis through NFκB/STAT3 pathway and protected against EAE pathology. Lastly, activation of A2AR in the cultured epithelium by A2AR overexpression or CGS21680 treatment increased the permeability of the CP epithelium and facilitated lymphocytes migration. CONCLUSION: These findings define the CP niche as one of the primary sites of A2AR action, whereby A2AR antagonists confer protection against EAE pathology. Thus, pharmacological targeting of the CP-A2AR represents a novel therapeutic strategy for MS by controlling immune cell trafficking across CP.

Validation of the Chinese version of the Hamilton Rating Scale for Depression in adults with epilepsy.

OBJECTIVE: This study aimed to validate the Chinese version of the 17-item Hamilton Rating Scale for Depression (C-HRSD-17) for use in adult patients with epilepsy (PWE). METHODS: A consecutive sample of Chinese adult PWE from a tertiary hospital was examined using the C-HRSD-17 and the Mini International Neuropsychiatric Interview (MINI) Plus Chinese Version 5.0.0. RESULTS: A total of 191 PWE completed the assessment of depression. According to the MINI, thirty patients (15.7%) had current major depressive disorder (MDD). The Cronbach's α coefficient for the C-HRSD-17 was 0.832. Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.983 (95% CI = 0.968-0.998). With a cutoff score of 9, the C-HRSD-17 demonstrated the best psychometric properties, with a sensitivity of 96.7%, a specificity of 93.8%, a positive predictive value (PPV) of 74.4%, and a negative predictive value (NPV) of 99.3%. CONCLUSION: The C-HRSD-17 proved to be a valid and reliable assessment tool, with a cutoff score of 9 for screening of current MDD in Chinese adult PWE.