Objective Neuroinflammation plays a critical role in central nervous system diseases. Exosomal miRNAs released from various cells are implicated in cell-to-cell communication. Prior studies have placed substantial emphasis on the role of cytokines in mast cell-microglia interactions during neuroinflammation. However, it has never been clearly determined whether exosomal miRNAs participate in the interaction between mast cells and microglia and thus mediate neuroinflammation. Methods The characteristics of exosomes isolated from cell culture supernatants were confirmed by transmission electron microscopy (TEM), nanoparticle-tracking analysis (NTA) and Western blot. The transfer of PKH67-labelled exosomes and Cy3-labelled miR-409-3p was observed by fluorescence microscopy. Migration and activation of murine BV-2 microglial cells were evaluated through Transwell assays and immunofluorescence staining for Iba1 and CD68. CD86, IL-1β, IL-6 and TNF-α were assessed via qRT-PCR and ELISA. MiR-409-3p was detected by qRT-PCR. Nr4a2 and NF-κB levels were measured by western blot. Regulatory effects were identified by luciferase reporter assays. Results Lipopolysaccharide (LPS)-stimulated murine P815 mast cells secreted exosomes that were efficiently taken up by murine BV-2 cells, which promoted murine BV-2 cell migration and activation. LPS-P815 exosomes increased the CD86, IL-1β, IL-6 and TNF-α levels in murine BV-2 microglia. Furthermore, activated mast cells delivered exosomal miR-409-3p to murine BV-2 microglia. Upregulated miR-409-3p promoted murine BV-2 microglial migration, activation and neuroinflammation by targeting Nr4a2 to activate the NF-κB pathway. Conclusion Exosomal miR-409-3p secreted from activated mast cells promotes microglial migration, activation and neuroinflammation by targeting Nr4a2 to activate the NF-κB pathway, which provides evidence that not only cytokines but also exosomal miRNAs participate in neuroinflammation. In the future, targeting exosomal miRNAs may provide new insights into neuroinflammation.
Background: The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the “first responders”, play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified.Methods: In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed KitW-sh mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again.Results: Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate.Conclusion: Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD.
Case series Patients: Male, 56-year-old • Male, 57-year-old Final Diagnosis: Trigeminocardiac reflex Symptoms: Bradycardia • severe hemodynamic fluctuation Medication: — Clinical Procedure: — Specialty: Anesthesiology • Neurosurgery Objective: Unusual clinical course Background: Trigeminocardiac reflex (TCR) is a unique brain stem reflex that manifests as the sudden onset of hemodynamic perturbation in heart rate and blood pressure as a result of stimulation of any branches of the trigeminal nerve. Onyx™ embolization in cerebrovascular interventional surgery can trigger TCR, leading to severe hemo-dynamic fluctuations and even cardiac arrest. Appropriate prophylactic approaches to prevent Onyx™ embolization-induced TCR are still lacking. Case Reports: We report the cases of 2 patients with recurrent and profound bradycardia due to TCR during endovascular Onyx™ embolization for a dural arteriovenous fistula. Prophylactic intra-arterial injection of lidocaine (10–20 mg) effectively and safely blocked the recurrence and potential occurrence of TCR. These 2 patients had reduced heart rate with either hypotension or hypertension during their TCR episodes, suggesting that stimulating a distinct cerebral artery (occipital artery versus vertebral artery branch) can initiate TCR by provoking the vagus nerve via the common neuronal pathway while simultaneously inhibiting or exciting the sympathetic pathway. Conclusions: Intra-arterial injection of lidocaine during endovascular procedures can be recommended as an effective prophylactic approach for use in the treatment of the cerebrovascular disorder where there is high risk of embolization-induced TCR.
Background Radiofrequency catheter ablation (RFCA) as a safe and effective method has been widely used in ventricular tachycardia (VT) patients, and with which anesthesiologists frequently manage their perioperative care. The aim of this study was to investigate the effects of different anesthetic depths on perioperative RFCA and recurrence in patients who with intractable VT and could not tolerate an awake procedure. Methods We reviewed electronic medical records of patients with VT who underwent RFCA by general anesthesia from January 2014 to March 2019. According to intraoperative VT induction, they were divided into two groups: non-inducible group (group N) and inducible group (group I). We constructed several multivariable regression models, in which covariates included patient characteristics, comorbidities, protopathy and bispectral index (BIS) value. Results One hundred one patients were analyzed. Twenty-nine patients (28.7%) experienced VT no induction, and 26 patients (25.7%) relapsed within 1 year. Compared with group I, the proportion of patients with arrhythmogenic right ventricular cardiomyopathy in group N were higher (P < 0.05), and the recurrence rate of VT was significantly higher (51.7% vs 15.3%) (P < 0.05). The BIS value in group N was significantly lower (P < 0.01), in addition, the BIS < 40 was associated with elevated odds of VT no induction compared with a BIS > 50 (odds ratio, 6.92; 95% confidence interval, 1.47–32.56; P = 0.01). VT no induction was an independent predictor of recurrence after RFCA (odds ratio, 5.01; 95% confidence interval, 1.88–13.83; P < 0.01). Conclusion Lower BIS value during VT induction in RFCA operation was associated with high risk of VT no induction, which affects postoperative outcomes. We proposed that appropriate depth of anesthesia should be maintained during the process of VT induction.
Schizophrenia (SZ) is a chronic and devastating mental illness that affects around 20 million individuals worldwide. Cognitive deficits and structural and functional changes of the brain, abnormalities of brain ECM components, chronic neuroinflammation, and devastating clinical manifestation during SZ are likely etiological factors shown by affected individuals. However, the pathophysiological events associated with multiple regulatory pathways involved in the brain of this complex disorder are still unclear. This study aimed to develop a pipeline based on bioinformatics and machine learning approaches for identifying potential therapeutic targets involving possible biological mechanisms from SZ patients and healthy volunteers. 420 overlapping DEGs from three RNA-seq datasets were identified. GO, and pathways analysis showed several biological mechanisms enriched by the commonly shared DEGs, including ECM organization, collagen fibril organization, integrin signaling pathway, inflammation mediated by chemokines and cytokines signaling pathway, and GABA-B receptor II and IL4 mediated signaling. 15 hub genes (FN1, COL1A1, COL3A1, COL1A2, COL5A1, COL2A1, COL6A2, COL6A3, MMP2, THBS1, DCN, LUM, HLA-A, HLA-C, and FBN1) were discovered by comprehensive analysis, which was mainly involved in the ECM organization and inflammatory signaling pathway. Furthermore, the miRNA target of the hub genes was analyzed with the random-forest-based approach software miRTarBase. In addition, the transcriptional factors and protein kinases regulating overlapping DEGs in SZ, namely, SUZ12, EZH2, TRIM28, TP53, EGR1, CSNK2A1, GSK3B, CDK1, and MAPK14, were also identified. The results point to a new understanding that the hub genes (fibronectin 1, collagen, matrix metalloproteinase-2, and lumican) in the ECM organization and inflammatory signaling pathways may be involved in the SZ occurrence and pathogenesis.
Background Trigeminocardiac reflex (TCR) is a brainstem reflexive response of hemodynamic instability during surgery. However, few risk factor analysis and management strategies of TCR have been highlighted in the literature. The purpose of this study was to demonstrate the risk factors for Onyx embolization during cerebrovascular intervention operation so as to optimize perioperative management and reduce the incidence of TCR. Methods We performed a retrospective study on consecutive patients with Onyx embolization over a 4-years period. According to whether TCR episode, they were divided into TCR group and control group. Cases and controls were compared regarding patient characteristics, comorbidities, hemodynamics and complications. We also constructed several multivariable regression models to analyze the risk factors. Results Among 195 identified patients, 27 patients (13.8%) occurred TCR. During DMSO/Onyx injection, HR and MAP were much lower in the TCR group than control group (P < 0.01). Notably, on univariable analysis, the patients with dural arteriovenous fistula (DAVF) and middle meningeal artery being affected was associated with a higher incidence of TCR (P < 0.01). On multivariable analysis, we also found that significant predictors of TCR were DAVF (OR = 12.78; 95%CI [3.57–45.68]), CCF (OR = 7.65; 95%CI [1.64–35.65]), the lesion which supplied by the middle meningeal artery (OR = 4.24; 95%CI [1.67–10.73]), and bradycardia before embolization (OR = 2.55; 95%CI [1.08–5.99]). Conclusion This study demonstrated that DAVF, CCF, and middle meningeal artery embolism may the risk factors for intraoperative TCR episode during Onyx endovascular embolization. Therefore, it is worth further study to take appropriate measures to block TCR-related risk factors during endovascular embolization. Trial registration: ChiCTR, ChiCTR2000038839; Registered 5 October 2020.
IntroductionTrigeminocardiac reflex (TCR) is a brainstem reflexive response of hemodynamic instability during surgery. Identification of risk factors relevant to TCR during cerebrovascular intervention procedures is helpful to efficiently prevent and treat its occurrence. The purpose of this study was to demonstrate the risk factors for Onyx embolization during cerebrovascular intervention operation so as to optimize perioperative management strategies on TCR.MethodsWe performed a retrospective study on the patients with Onyx embolization under general anaesthesia over 6-years period from 2013 to 2018. 354 patients were finally eligible for inclusion, and then divided into TCR group (group T) and control group (group N). Patient characteristics, clinical diagnosis, comorbidities, lesion sites, hemodynamics changes, and complications were compared between two groups. Several multivariable regression models were applied to analyze the risk factors associated with TCR.ResultsTCR occurred in 59 patients (16.7%) among 354 patients. There was no significant difference in patient characteristics between two groups (P > 0.05). During DMSO/Onyx injection, HR and MAP were much lower in group T than group N (P < 0.01). Notably, univariable analysis revealed that the patients with dural arteriovenous fistula (DAVF) and middle meningeal artery being affected were associated with a higher incidence of TCR (P < 0.01). Furthermore, multivariable analysis showed that there was a close link of TCR with DAVF [OR = 4.12; 95% CI (1.83–10.65)] and middle meningeal artery embolization [OR = 3.90; 95% CI (1.58–9.63)]. Further stratified analysis of patients with TCR found that patients with middle meningeal artery embolization were more likely to experience hypotension during TCR episode (P < 0.05). Finally, more incidence of postoperative adverse events was observed when TCR episode (P < 0.05).ConclusionWe found that DAVF and middle meningeal artery embolization were independent risk factors for TCR episodes during Onyx endovascular embolization, highly likely leading to intraoperative hemodynamics fluctuations and postoperative adverse events.
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