Effect of a single sub-anesthetic dose of ketamine on postoperative fatigue syndrome in patients after laparoscopic radical resection of colorectal cancer: a randomized controlled trial
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2707616 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Acute fetal hypoxia is a form of fetal stress that stimulates renal vasoconstriction and ischemia as a consequence of the physiological redistribution of combined ventricular output. We have demonstrated that hypoxia in late ovine gestation induces inflammation in the brain that is ameliorated by treatment with ketamine. We hypothesized that the fetal kidney would also respond to hypoxia with an increase in the expression of inflammatory genes, and that ketamine (an N-Methyl-D-aspartate receptor antagonist) would reduce or block this response. Enriched biological processes for the 427 upregulated genes were immune and inflammatory responses and for the 946 down-regulated genes were metabolic processes. Ketamine countered the effects of hypoxia on upregulated immune/inflammatory responses as well as the down-regulated metabolic responses. We conclude that our transcriptomics modeling predicts that hypoxia activates inflammatory pathways and reduces metabolism in the fetal kidney cortex, and ketamine blocks or ameliorates this response. The results suggest that ketamine may have therapeutic potential for protection from ischemic renal damage. At the time of surgery, fetuses were randomly assigned to one of the four groups (n=3-4/group): normoxic control, normoxia+ketamine, hypoxic control, and hypoxia+ketamine. Hypoxia was induced for 30 min in chronically catheterized fetal sheep (125±3 d; term=145-147d), with or without ketamine (3 mg/kg) administered intravenously to the fetus 10 min prior to hypoxia. Fetuses were euthanized 24 hours after the onset of hypoxia, and the kidney cortex were collected for RNA extraction and gene array studies. Gene expression was analyzed using ovine Agilent 15.5 k array and validated with qPCR. Significant differences in gene expression between groups were determined with t-statistics using the limma package for R (Pâ¤0.05).
2016-09-01 | E-GEOD-66920 | biostudies-arrayexpress
Project description:We established the ketamine-induced cystitis (KIC) models in female Sprague-Dawley rats. The bladder of the ketamine group and the control group were obtained to perform transcriptome analysis.
2022-02-28 | GSE189809 | GEO
Project description:Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. The chemoreceptor reflex that is responsible for this physiological response is dependent on glutamatergic neurotransmission which, in times of vigorous activity, could produce cell death secondary to calcium uptake. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the hippocampus and that ketamine, an antagonist of NMDA receptors, reduces the damage. Late-gestation, chronically catheterized fetal sheep were subjected to a 30 min period of ventilatory hypoxia that decreased fetal PaO2 from 17±1 to 10±1 mm Hg, or normoxia (PaO2 17±1 mm Hg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, iv). One day (24 h) after hypoxia/normoxia, fetal hippocampus was removed and mRNA extracted for transcriptomics and systems biology analysis. Hypoxia stimulated a transcriptomics response consistent with a an increase in inflammation (e.g., cytokine binding and response to LPS). Ketamine pretreatment reduced these responses. The inflammation response modeled with transcriptomic system biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the hippocampal tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal hippocampus and that ketamine, in a standard clinical dose, reduces the inflammation response.
2017-08-31 | GSE97916 | GEO
Project description:Interventions: ketamine group:ketamine ;control group:Blank control
Primary outcome(s): HAD;cytokine
Study Design: Randomized parallel controlled trial
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Project description:Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder caused by mutations in the ADNP gene, resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD). Ketamine treatment has emerged as a promising therapeutic option for children with ADNP syndrome, showing safety and significant behavioral improvements. However, the underlying molecular perturbations caused by ketamine remain poorly described. We dissected the longitudinal effect of ketamine on the peripheral blood transcriptome of 10 individuals with ADNP syndrome. The blood transcriptome was profiled prior-to intravenous ketamine treatment (0.5mg/kg) and then again at five post-infusion timepoints: immediately post-infusion, day 1, week 1, week 2, and week 4. We show that a single low-dose infusion of ketamine triggers immediate and profound gene expression alterations, with specific enrichment of monocyte-related expression patterns. These alterations encompass diverse signaling pathways and co-expression networks, implicating up-regulation of immune and inflammatory-related processes and down-regulation of RNA processing mechanisms and metabolism. Notably, these changes exhibit a transient nature, returning to baseline levels 24 hours to 1 week after treatment. These findings advance our understanding of ketamine's molecular effects and provides a foundation for further research in elucidating its precise cellular and molecular targets. Moreover, the comprehensive assessment of ketamine-induced changes in ADNP syndrome contributes to the development of innovative therapeutic strategies for this challenging genetic disorder.
2023-07-02 | GSE235921 | GEO
Project description:Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. The chemoreceptor reflex that is responsible for this physiological response is dependent on glutamatergic neurotransmission which, in times of vigorous activity, could produce cell death secondary to calcium uptake. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors, reduces the damage. Late-gestation, chronically catheterized fetal sheep were subjected to a 30 min period of ventilatory hypoxia that decreased fetal PaO2 from 17±1 to 10±1 mm Hg, or normoxia (PaO2 17±1 mm Hg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, iv). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis. Hypoxia stimulated a transcriptomics response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic system biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response.
2016-04-06 | GSE76110 | GEO
Project description:Ketamine has rapid and sustained antidepressant effects in patients with treatment resistant depression (TRD). However, the underlying mechanisms of action are not well understood. There is increasing evidence that TRD is associated with a pro-inflammatory state and that ketamine may inhibit inflammatory cytokine production. We investigated whole blood transcriptional profiles related to TRD and gene expression changes associated with treatment response to ketamine. Whole blood was collected at baseline (21 healthy controls [HC], 26 patients with TRD) and then again in patients with TRD 24 hours following a single intravenous infusion of ketamine (0.5 mg/kg). We performed RNA-sequencing and compared a) baseline transcriptional profiles between patients with TRD and HC, b) responders vs. non-responders before ketamine treatment, and c) gene expression signatures associated with clinical improvement. At baseline, patients with TRD compared to HC were characterized by a gene expression signature indicative of interferon signaling pathway activation. Prior to ketamine administration, the metabotropic glutamate receptor gene GRM2 and the ionotropic glutamate receptor gene GRIN2D were upregulated in responders compared to non-responders. Ketamine response was associated with the downregulation of multiple genes coding for pro-inflammatory cytokines, the predicted inhibition of several interferon signaling associated upstream regulators and the downregulation of Indoleamine 2,3-Dioxygenase 1 (IDO1). The current study indicates that response to ketamine may be associated with up-regulation of glutamate receptors at baseline, and linked to transcriptional changes indicative of an anti-inflammatory response following ketamine. One specific anti-inflammatory mechanism might be the downregulation of IDO1 via inhibition of the interferon pathway.
2021-10-13 | GSE185855 | GEO
Project description:Patients with schizophrenia show increased striatal dopamine synthesis capacity in imaging studies. However, the mechanism underlying this is unclear but may be due to N-methyl-D-aspartate receptor (NMDAR) hypofunction and parvalbumin (PV) neuronal dysfunction leading to disinhibition of mesostriatal dopamine neurons. Here, we test this in a translational mouse imaging study using a ketamine model. Mice were treated with sub-chronic ketamine (30mg/kg) or saline followed by in-vivo positron emission tomography of striatal dopamine synthesis capacity, analogous to measures used in patients. Locomotor activity was measured using the open field test. In-vivo cell-type-specific chemogenetic approaches and pharmacological interventions were used to manipulate neuronal excitability. Immunohistochemistry and RNA sequencing were used to investigate molecular mechanisms. Sub-chronic ketamine increased striatal dopamine synthesis capacity (Cohen’s d=2.5) and locomotor activity. These effects were countered by inhibition of midbrain dopamine neurons, and by activation of cortical and ventral subiculum PV interneurons. Sub-chronic ketamine reduced PV expression in these neurons. Pharmacological intervention with SEP-363856, a novel psychotropic agent with agonism at trace amine receptor 1 (TAAR1), significantly reduced the ketamine-induced increase in dopamine synthesis capacity. These results show that sub-chronic ketamine treatment in mice mimics the dopaminergic alterations in patients with psychosis, and suggest an underlying neurocircuit involving PV interneuron hypofunction in frontal cortex and hippocampus as well as activation of midbrain dopamine neurons. A novel TAAR1 agonist reversed the dopaminergic alterations suggesting a therapeutic mechanism for targeting presynaptic dopamine dysfunction in patients.
2021-02-16 | GSE138802 | GEO
Project description:Ketamine has been found to elicit a rapid antidepressant effects in treatment-refractory affective disorders. To indicate the underlying mechanism of action we have performed whole-genome microarray profiling. Moreover, the effects of ketamine were compared to other NMDA receptor antagonists phencyclidine and memantine. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Ketamine, NMDA antagonist, Phencyclidyne, Memantine, Time-course, Gene Expression, Acute treatment The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse hippocampus. Three NMDA antagonists (ketamine 20 mg/kg, phencyclidine 5 mg/kg and memantine 15 mg/kg i.p.) were selected for the comparison. Drug doses were based on the literature. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naive animals were prepared for each time point. Samples from 2 mice were pooled per microarray, 3 biological replicates were used per time point and 12 arrays per each drug. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.
2015-12-31 | E-GEOD-73798 | biostudies-arrayexpress
Project description:Ketamine has been found to elicit a rapid antidepressant effects in treatment-refractory affective disorders. To indicate the underlying mechanism of action we have performed whole-genome microarray profiling. Moreover, the effects of ketamine were compared to other NMDA receptor antagonists phencyclidine and memantine. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Ketamine, NMDA antagonist, Phencyclidyne, Memantine, Time-course, Gene Expression, Acute treatment The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Three NMDA antagonists (ketamine 20 mg/kg, phencyclidine 5 mg/kg and memantine 15 mg/kg i.p.) were selected for the comparison. Drug doses were based on the literature. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naive animals were prepared for each time point. Samples from 2 mice were pooled per microarray, 3 biological replicates were used per time point and 12 arrays per each drug. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.
2015-12-31 | E-GEOD-73799 | biostudies-arrayexpress