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Effects of compound 21, a non?peptide angiotensin II type 2 receptor agonist, on general anesthesia?induced cerebral injury in neonatal rats.

ABSTRACT: General anesthesia has a great impact on neurodevelopment. However, the mechanisms underlying this effect and therapeutic methods to address it remain limited. The present study aimed to investigate the effects of compound (C)21, a non?peptide angiotensin II type 2 receptor agonist, on general anesthesia?induced cerebral injury in neonatal rats. Neonatal Sprague Dawley rats (postnatal day 7) were randomly divided into three groups (n=6 per group): The control, isoflurane and C21+ isoflurane (C21) group. General anesthesia was induced through inhalation of 1.3% isoflurane. Apoptosis and synaptic structure were analyzed. The levels of peroxisome proliferator?activated receptor (PPAR)?? were detected using an enzyme?linked immunosorbent assay. BCL2, apoptosis regulator (Bcl?2) expression was also measured. Compared with the control group, the cerebral cortex, hippocampus, amygdala and hypothalamus in the isoflurane group had significantly more apoptotic cells (P<0.05). The nuclei of the control group were round and transparent, while shrunken nuclei and condensed chromatin were visible in the isoflurane group. A reduction in synapse number was observed in the isoflurane group compared with the control. By contrast, nuclei shrinkage and the decrease in synaptic number was improved in the C21 group. PPAR?? and Bcl?2 expression, at the mRNA and protein levels, was significantly reduced in the isoflurane group compared with the control (P<0.05). C21 treatment reduced the decrease in PPAR?? and Bcl?2 in the cerebral cortex, hippocampus, amygdala and hypothalamus (P<0.05). Collectively, it was demonstrated that C21 prevented apoptosis and synaptic loss induced by general anesthesia in neonatal rats by enhancing the expression of PPAR?? and Bcl?2.

SUBMITTER: Yong J

PROVIDER: S-EPMC6236271 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Effects of compound 21, a non‑peptide angiotensin II type 2 receptor agonist, on general anesthesia‑induced cerebral injury in neonatal rats.

Yong Jun J Yan Li L Wang Jing J Xiao Hongmei H Zeng Qingfan Q

Molecular medicine reports 20181026 6

General anesthesia has a great impact on neurodevelopment. However, the mechanisms underlying this effect and therapeutic methods to address it remain limited. The present study aimed to investigate the effects of compound (C)21, a non‑peptide angiotensin II type 2 receptor agonist, on general anesthesia‑induced cerebral injury in neonatal rats. Neonatal Sprague Dawley rats (postnatal day 7) were randomly divided into three groups (n=6 per group): The control, isoflurane and C21+ isoflurane (C21 ...[more]

PMID: 30365086

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Project description:Cerebral oxygen saturation (rSO2c) decrease from baseline greater than 20 % during infant cardiac surgery was associated with postoperative neurologic changes and neurodevelopmental impairment at 1 year of age. So far, there is no sufficient evidence to support the routine monitoring of rSO2c during general surgical procedures in children. We aimed to find out the frequency of cerebral desaturation 20 % or more from baseline and to identify possible predictors of change in cerebral oxygen saturation during neonatal and infant general surgery.Forty-four infants up to 3 months of age were recruited. Before induction of anesthesia, two pediatric cerebral sensors were placed bilaterally to the forehead region and monitoring of regional cerebral saturation of oxygen was started and continued throughout the surgery. Simultaneously, mean arterial blood pressure (MAP), pulse oximetry (SpO2), heart rate (HR), endtidal CO2, expired fraction of sevoflurane and rectal temperature were recorded. The main outcome measure was rSO2c value drop-off ?20 % from baseline. Mann-Whitney U-test, chi-squared test, simple and multiple linear regression models were used for statistical analysis.Forty-three infants were analyzed. Drop-off ?20 % in rSO2c from baseline occurred in 8 (18.6 %) patients. There were no differences in basal rSO2c, SpO2, HR, endtidal CO2, expired fraction of sevoflurane and rectal temperature between patients with and without desaturation 20 % or more from baseline. But the two groups differed with regard to gestation, preoperative mechanical ventilation and the use of vasoactive medications and red blood cell transfusions during surgery. Simple linear regression model showed, that gestation, age, preoperative mechanical ventilation and mean arterial pressure corresponding to minimal rSO2c value during anesthesia (MAPminrSO2c) were associated with a change in rSO2c values. Multiple regression model including all above mentioned variables, revealed that only MAPminrSO2c was predictive for a change in rSO2c values (? (95 % confidence interval) -0.28 (-0.52-(-0.04)) p?=?0.02).Cerebral oxygen desaturation ?20 % from baseline occurred in almost one fifth of patients. Although different perioperative factors can predispose to cerebral oxygenation changes, arterial blood pressure seems to be the most important. Gestation as another possible risk factor needs further investigation.The international registration number NCT02423369 . Retrospectively registered on April 2015.

Project description:PurposeTo assess the feasibility of ferumoxytol-enhanced anesthesia-free cardiac MRI in neonates and young infants for complex congenital heart disease (CHD).Materials and methodsWith Institutional Review Board approval, 21 consecutive neonates and young infants (1 day to 11 weeks old; median age of 3 days) who underwent a rapid two-sequence (MR angiography [MRA] and four-dimensional [4D] flow) MRI protocol with intravenous ferumoxytol without sedation (n = 17) or light sedation (n = 4) at 3 Tesla (T) (except one case at 1.5T) between June 2014 and February 2016 were retrospectively identified. Medical records were reviewed for indication, any complications, if further diagnostic imaging was performed after MRI, and surgical findings. Two radiologists scored the images in two sessions on a 5-point scale for overall image quality and delineation of various anatomical structures. Confidence interval of proportions for likelihood of requiring additional diagnostic imaging after MRI was determined. For the possibility of reducing the protocol to a single rapid sequence, Wilcoxon-rank sum test was used to assess whether 4D flow and MRA significantly differed in anatomical delineation.ResultsOne of 21 patients (4.8%, 80% confidence interval 0-11%) required additional imaging, a computed tomography angiography to assess lung parenchyma and peripheral pulmonary arteries. Only 1 of 13 patients (7.7%) with operative confirmation had a minor discrepancy between radiology and operative reports (80% confidence interval 0-17%). 4D flow was significantly superior to MRA (P < 0.05) for the evaluation of systemic arteries, valves, ventricular trabeculae, and overall quality. Using Cohen's kappa coefficient, there was good interobserver agreement for the evaluation of systemic arteries by 4D flow (κ = 0.782), and systemic veins and pulmonary arteries by MRA (κ > 0.6). Overall 4D flow measurements (mean κ = 0.64-0.74) had better internal agreement compared with MRA (mean κ = 0.30-0.64).ConclusionFerumoxytol-enhanced cardiac MRI, without anesthesia, is feasible for the evaluation of complex CHD in neonates and young infants, with a low likelihood of need for additional diagnostic studies. The decreased risk by avoiding anesthesia must be balanced against the potential for adverse reactions with ferumoxytol.Level of evidence2 J. MAGN. RESON. IMAGING 2017;45:1407-1418.

Dataset Information

Effects of compound 21, a non?peptide angiotensin II type 2 receptor agonist, on general anesthesia?induced cerebral injury in neonatal rats.

Publications

Effects of compound 21, a non‑peptide angiotensin II type 2 receptor agonist, on general anesthesia‑induced cerebral injury in neonatal rats.

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