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1.
Behav Brain Res ; 459: 114792, 2024 02 29.
Article in English | MEDLINE | ID: mdl-38048914

ABSTRACT

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with traumatic stress experiences. This condition can be accompanied by learning and cognitive deficits. Studies have demonstrated that ketamine can rapidly and significantly alleviate symptoms in patients with chronic PTSD. Nonetheless, the effects of ketamine on neurocognitive impairment and its mechanism of action in PTSD remain unclear. METHODS: In this study, different concentrations of ketamine (5, 10, 15, and 20 mg/kg, i.p.) were evaluated in rat models of single prolonged stress and electrophonic shock (SPS&S). Expression levels of brain-derived neurotrophic factor (BDNF) and post-synaptic density-95 (PSD-95) in the hippocampus (HIP) and amygdala (AMG) were determined by Western blot analysis and immunohistochemistry. RESULTS: The data showed that rats subjected to SPS&S exhibited significant PTSD-like cognitive impairment. The effect of ketamine on SPS&S-induced neurocognitive function showed a U-shaped dose effect in rats. A single administration of ketamine at a dosage of 10-15 mg/kg resulted in significant changes in behavioral outcomes. These manifestations of improvement in cognitive function and molecular changes were reversed at high doses (15-20 mg/kg). CONCLUSION: Overall, ketamine reversed SPS&S-induced fear and spatial memory impairment and the down-regulation of BDNF and BDNF-related PSD-95 signaling in the HIP and AMG. A dose equal to 15 mg/kg rapidly reversed the behavioral and molecular changes and promoted the amelioration of cognitive dysfunction. The enhanced association of BDNF signaling with PSD-95 effects could be involved in the therapeutic efficiency of ketamine for PTSD.


Subject(s)
Cognitive Dysfunction , Ketamine , Stress Disorders, Post-Traumatic , Humans , Rats , Animals , Brain-Derived Neurotrophic Factor/metabolism , Stress Disorders, Post-Traumatic/complications , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/metabolism , Ketamine/metabolism , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Hippocampus/metabolism , Amygdala/metabolism , Cognition , Signal Transduction/physiology , Fear , Disease Models, Animal
2.
Brain Res Bull ; 200: 110697, 2023 08.
Article in English | MEDLINE | ID: mdl-37392896

ABSTRACT

RATIONALE: Post-traumatic stress disorder (PTSD) is a complex, chronic psychiatric disorder typically triggered by life-threatening events and, as yet, lacks a specialized pharmacological treatment. The potential therapeutic role of ketamine, an N-methyl-D-aspartate receptor antagonist, in mitigating PTSD has been the subject of investigation. OBJECTIVE: The aim of this study was to elucidate alterations in the glycogen synthase kinase-3ß (GSK-3ß) signaling pathway in response to ketamine intervention, using the single prolonged stress (SPS) model of PTSD at a molecular level. METHODS: PTSD-like symptoms were simulated using the SPS model. Ketamine (10 mg/kg) and GSK-3ß antagonist SB216763 (5 mg/kg) were then administered intraperitoneally. Stress-related behavior was evaluated through the open field test (OFT) and the elevated plus maze test (EMPT). Additionally, brain activity was analyzed using quantitative electroencephalography (qEEG). Changes in protein and mRNA expressions of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), GSK-3ß, phosphorylated ser-9 GSK-3ß (p-GSK-3ß), FK506 binding protein 5 (FKBP5), and corticotropin-releasing hormone (CRH) were assessed in the hypothalamus via western blot and qPCR. RESULTS: SPS-exposed rats exhibited reduced distance and time spent in the center of the open arms, a pattern divergent from control rats. qEEG readings revealed SPS-induced increases in alpha power, low gamma and high gamma power. Furthermore, SPS triggered an upregulation in the protein and gene expression of GSK-3ß, GR, BDNF, p-GSK-3ß, and FKBP5, and downregulated CRH expression in the hypothalamus. Ketamine administration following the SPS procedure counteracted these changes by increasing the time spent in the center of the OFT, the distance traversed in the open arms of the EMPT, and mitigating SPS-induced alterations in cerebral cortex oscillations. Moreover, ketamine reduced the protein levels of GSK-3ß, GR, p-GSK-3ß, and altered the ratio of p-GSK-3ß to GSK-3ß. Gene expression of GSK-3ß, GR, BDNF, and FKBP5 decreased in the SPS-Ket group compared to the SPS-Sal group. CONCLUSIONS: Ketamine appeared to remediate the abnormal GSK-3ß signaling pathway induced by SPS. These findings collectively suggest that ketamine could be a promising therapeutic agent for PTSD symptoms, working through the modulation of the GSK-3ß signaling pathway.


Subject(s)
Ketamine , Stress Disorders, Post-Traumatic , Rats , Animals , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/metabolism , Rodentia/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Ketamine/pharmacology , Glycogen Synthase Kinase 3 beta/metabolism , Signal Transduction , Corticotropin-Releasing Hormone
3.
Front Oncol ; 12: 939358, 2022.
Article in English | MEDLINE | ID: mdl-36465384

ABSTRACT

Purpose: To evaluate preoperative diffusion kurtosis imaging (DKI) in predicting the outcomes of large hepatocellular carcinoma (HCC) after liver resection (LR). Materials and methods: From January 2015 to December 2017, patients with a large (≥5cm) HCC who underwent preoperative DKI were retrospectively reviewed. The correlations of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) with microvascular invasion (MVI) or histological grade were analyzed. Cox regression analyses were performed to identify the predictors of recurrence-free survival (RFS) and overall survival (OS). A nomogram to predict RFS was established. P<0.05 was considered as statistically significant. Results: A total of 97 patients (59 males and 38 females, 56.0 ± 10.9 years) were included in this study. The MK, MD, and ADC values were correlated with MVI or histological grade (P<0.01). With a median follow-up time of 41.2 months (range 12-69 months), 67 patients (69.1%) experienced recurrence and 41 patients (42.3%) were still alive. The median RFS and OS periods after LR were 29 and 45 months, respectively. The 1-, 3-, and 5-year RFS and OS rates were 88.7%, 41.2%, and 21.7% and 99.0%, 68.3%, and 25.6%, respectively. MK (P<0.001), PVT (P<0.001), and ADC (P=0.033) were identified as independent predictor factors for RFS. A nomogram including the MK value for RFS showed the best performance, and the C-index was 0.895. Conclusion: The MK value obtained from DKI is a potential predictive factor for recurrence and poor survival, which could provide valuable information for guiding the efficacy of LR in patients with large HCC.

4.
Int J Clin Exp Med ; 8(8): 14416-23, 2015.
Article in English | MEDLINE | ID: mdl-26550429

ABSTRACT

PE (Pulmonary embolism, PE) is a common disease, usually caused by blockage of pulmonary artery and its branches due to exogenous or endogenous embolic obstruction. PE always be misdiagnosed in clinical. The aim of this study is to calculate the sensitivity and specificity of magnetic resonance imaging (MRI) in assessing the resectability of PE. In this study, a meta-analysis of the reported sensitivity and specificity of each study with 95% confidence intervals (CI) was performed. Five studies were included in the meta-analysis. The results indicated that the quality assessment scores ranged from 11 to 13, with a mean study quality score of 12. The sensitivity and specificity values including 95% CI at the patient level were calculated. The sensitivities ranged from 78% to 100%, and the specificity ranged from 99% to 100%. The pooled sensitivity value including 95% CI was 0.83 (0.78-0.88), and with inconsistency (I (2)) of 62.8%. The pooled specificity value including 95% CI was 0.99 (0.98-1.00), with inconsistency (I(2)) of 0.0%. Pooled positive likelihood ratio (PLR) (95% CI) was 70.22 (29.04-169.76), and the pooled negative likelihood ratio (NLR) (95% CI) was 0.19 (0.14-0.25). The overall diagnostic odds ratio (DOR) (95% CI) was 448.98 (163.47-1233.18). The summary receiver operating characteristic (SROC) data illustrated that the area under the curve (AUC) was 0.9852. In conclusion, the MRI method may be acts as a potential and assistant method for the PE diagnosis.

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