OBJECTIVES
The medial prefrontal cortex (mPFC) is a cortical brain region that involved in various emotional disorder. Neuroinflammation and oxidative stress are reported to associated with the pathogenesis of anxiety, but the underlying brain mechanisms remain unclear.
METHODS AND RESULTS
Here, using a mouse model of chronic restraint stress (CRS), we found that the stress-induced anxiety-like behavior is accompanied with enhanced neuroinflammation and oxidative stress in mPFC. Specifically, we found that the expression of Dkk3, a dickkopf Wnt signaling pathway regulator, was significantly decreased in the stressed human participants and CRS model mice. Dkk3 deficiency increased neuroinflammation and oxidative stress, impaired the neuronal synaptic plasticity, decreased the neural network synchronization, and thereby contributing to anxiety-like behaviors via RhoA/Rock2/NF-κB signaling pathway. However, overexpression of Dkk3 or pharmacological prevent the RhoA/Rock2/NF-κB signaling pathway in the stressed mice could significantly rescue neural injury and anxiety-like phenotypes.
CONCLUSION
Taken together, this study reveal that Dkk3 may plays a critical role within the stress-induced behavioral deficits via regulating neuroinflammation and oxidative stress to maintain neural-activity homeostasis, through which may serve as a potential therapeutic target for the treatment of anxiety disorders.
Xiao Chen, Ruojing Guo, Changmin Wang et al.· Journal of Advanced Research· 0 citations
Purpose Hemodynamic instability during tracheal intubation in elderly patients poses significant perioperative risks. This study aimed to determine the effective doses (ED50/ED95) of remifentanil combined with remimazolam to suppress intubation-induced stress responses while minimizing hypotension in patients aged ≥60. Patients and Methods In this prospective, double-blind trial, 29 elderly patients received remimazolam (0.3 mg/kg) followed by rocuronium and remifentanil (initial dose: 1 µg/kg, adjusted via Dixon’s up-down method). Hemodynamic parameters (blood pressure, heart rate, systemic vascular resistance, cardiac output) and bispectral index (BIS) were recorded. Probit regression analyzed dose–response relationships. A positive hemodynamic response was defined as an increase in systolic blood pressure or heart rate exceeding 20% of the baseline value within 5 minutes after endotracheal intubation. Dixon’s up-and-down method and probit regression analysis to determine the ED50 and ED95 of remifentanil combined with remimazolam to suppress intubation-induced stress responses in elderly patients. Results The ED50 and ED95 of remifentanil were 0.85 µg/kg (95% CI: 0.80–0.90) and 0.97 µg/kg (95% CI: 0.91–1.21), respectively. Positive responders showed elevated blood pressure at 30s–1 min post-intubation (P<0.05), while cardiac output and systemic vascular resistance remained comparable between groups. Hypotension incidence was low (14.3–20%), with transient BIS elevations (60–70) in 51.7% of patients but no intraoperative awareness. Conclusion In this exploratory dose-finding study, the estimated ED50 and ED95 of remifentanil for suppressing intubation-related hemodynamic responses during remimazolam-based induction were 0.85 and 0.97 μg/kg, respectively.
Yue Ma, Jianting Huang, Haipeng Zhou et al.· Clinical Interventions in Ag...· 0 citations
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