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Apoptosis inhibition is involved in improvement of sevoflurane-induced cognitive impairment following normobaric hyperoxia preconditioning in aged rats.

ABSTRACT: Sevo?urane, a commonly used anesthetic agent has been confirmed to induce cognitive impairment in aged rats. Normobaric hyperoxia preconditioning has been demonstrated to induce neuroprotection in rats. The present study aimed to determine whether normobaric hyperoxia preconditioning could ameliorate cognitive deficit induced by sevoflurane and the possible mechanism by which it may exert its effect. A total of 66, 20-month-old male Sprague-Dawley rats were randomly divided into 3 groups (n=22 each): Rats in the control (C) and sevoflurane anesthesia (S) groups received no normobaric hyperoxia preconditioning before sevoflurane exposure, rats in the normobaric hyperoxia pretreatment (HO) group received normobaric hyperoxia preconditioning before sevoflurane exposure (95% oxygen for 4 continuous h daily for 6 consecutive days). The anesthesia rats (S and HO groups), were exposed to 2.5% sevoflurane for 5 h, while the sham anesthesia rats (C group) were exposed to no sevoflurane. The neurobehavioral assessment was performed using a Morris water maze test, the expressions of the apoptosis proteins were determined using western blot analysis, and the apoptosis rate and cytosolic calcium concentration were measured by flow cytometry. Normobaric hyperoxia preconditioning improved prolonged escape latency and raised the number of platform crossings induced by sevoflurane in the Morris water maze test, increased the level of bcl-2 protein, and decreased the level of bax and active caspase-3 protein, the apoptosis rate and cytosolic calcium concentration in the hippocampus 24 h after sevoflurane exposure. The findings of the present study may imply that normobaric hyperoxia preconditioning attenuates sevoflurane-induced spatial learning and memory impairment, and this effect may be partly related to apoptosis inhibition in the hippocampus. In conclusion, normobaric hyperoxia preconditioning may be a promising strategy against sevoflurane-induced cognitive impairment by inhibiting the hippocampal neuron apoptosis.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7818554 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Apoptosis inhibition is involved in improvement of sevoflurane-induced cognitive impairment following normobaric hyperoxia preconditioning in aged rats.

Wang Ying Y Yin Chun-Ping CP Tai Yan-Lei YL Zhao Zi-Jun ZJ Hou Zhi-Yong ZY Wang Qiu-Jun QJ

Experimental and therapeutic medicine 20210111 3

Sevoﬂurane, a commonly used anesthetic agent has been confirmed to induce cognitive impairment in aged rats. Normobaric hyperoxia preconditioning has been demonstrated to induce neuroprotection in rats. The present study aimed to determine whether normobaric hyperoxia preconditioning could ameliorate cognitive deficit induced by sevoflurane and the possible mechanism by which it may exert its effect. A total of 66, 20-month-old male Sprague-Dawley rats were randomly divided into 3 groups (n=22 e ...[more]

PMID: 33500697

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Project description:The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell?survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24 g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI group underwent 45 min clamping of the left renal vasculature, followed by 4 h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15 min. IPC included three cycles of two?min clamping and five?min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription?quantitative polymerase chain reaction (RT?qPCR) testing and their target pathways with Ingenuity Pathway Analysis™. The present study found that serum creatinine values in APC (0.71±0.08 mg/dl) and IPC (0.73±0.1 mg/dl) groups were lower than in the IRI group (0.96±0.13 mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT?qPCR followed by pathway analysis indicated that APC and IPC affect 'protein kinase B (Akt)'. APC promoted miR?17?3p and suppressed miR?27a. IPC promoted miR?19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell?protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome 10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3?kinase/Akt signaling pathway, resulting in reno?protection.

Project description:Background and purposeDamage of the blood-brain barrier (BBB) increases the incidence of neurovascular complications, especially for cerebral hemorrhage after tPA (tissue-type plasminogen activator) therapy. Currently, there is no effective method to evaluate the extent of BBB damage to guide tPA use. Herein, we investigated whether blood levels of tight junction proteins could serve as biomarker of BBB damages in acute ischemic stroke (AIS) in both rats and patients. We examined whether this biomarker could reflect the extent of BBB permeability during cerebral ischemia/reperfusion and the effects of normobaric hyperoxia (NBO) on BBB damage.MethodsRats were exposed to NBO (100% O2) or normoxia (21% O2) during middle cerebral artery occlusion. BBB permeability was determined. Occludin and claudin-5 in blood and cerebromicrovessels were measured. Patients with AIS were assigned to oxygen therapy or room air for 4 hours, and blood occludin and claudin-5 were measured at different time points after stroke.ResultsCerebral ischemia/reperfusion resulted in the degradation of occludin and claudin-5 in microvessels, leading to increased BBB permeability in rats. In blood samples, occludin increased with 4-hour ischemia and remained elevated during reperfusion, correlating well with its loss from ischemic cerebral microvessels. NBO treatment both prevented occludin degradation in microvessels and reduced occludin levels in blood, leading to improved neurological functions in rats. In patients with AIS receiving intravenous tPA thrombolysis, the blood occludin was already elevated when patients arrived at hospital (within 4.5 hours since symptoms appeared) and remained at a high level for 72 hours. NBO significantly lowered the level of blood occludin and improved neurological functions in patients with AIS.ConclusionsBlood occludin may be a clinically viable biomarker for evaluating BBB damage during ischemia/reperfusion. NBO therapy has the potential to reduce blood occludin, protect BBB, and improve outcome in AIS patients with intravenous tPA thrombolysis.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02974283.

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Project description:Background and objective: This is the first study to investigate the effect of high-flow oxygen therapy, using a normobaric chamber on cognitive, biochemical (oxidative stress parameters and the level of neurotrophins), cardiovascular and autonomic functioning. Materials and methods: 17 healthy volunteers, eight males and nine females, with a mean age of 37.5 years, were examined. The experimental study involved ten two-hour exposures in a normobaric chamber with a total pressure of 1500 hPa, in air adjusted to 37% oxygen, 1.079% carbon dioxide and 0.44% hydrogen. Cognitive function was assessed by using Trail Making Test parts A, B and difference in results of these tests (TMT A, TMT B and TMT B-A); California Verbal Learning Test (CVLT); Digit symbol substitution test (DSST); and Digit Span (DS). Fatigue (Fatigue Severity Scale (FSS)), cardiovascular, autonomic and baroreceptor functioning (Task Force Monitor) and biochemical parameters were measured before and after intervention. Results: After 10 sessions in the normobaric chamber, significant decreases in weight, caused mainly by body fat % decrease (24.86 vs. 23.93%, p = 0.04 were observed. TMT part A and B results improved (p = 0.0007 and p = 0.001, respectively). In contrast, there was no statistically significant influence on TMT B-A. Moreover, decrease in the number of symbols left after a one-minute test in DSST was noted (p = 0.0001). The mean number of words correctly recalled in the CVLT Long Delay Free Recall test improved (p = 0.002), and a reduction in fatigue was observed (p = 0.001). Biochemical tests showed a reduction in levels of malondialdehyde (p < 0.001), with increased levels of Cu Zn superoxide dismutase (p < 0.001), Neurotrophin 4 (p = 0.0001) and brain-derived neurotrophic factor (p = 0.001). A significant increase in nitric oxide synthase 2 (Z = 2.29, p = 0.02) and Club cell secretory protein (p = 0.015) was also noted. Baroreceptor function was significantly improved after normobaric exposures (p = 0.003). Significant effect of normobaric exposures and BDNF in CVLT Long Delay Free Recall was noted. Conclusions: This study demonstrates that 10 exposures in a normobaric chamber have a positive impact on visual information and set-shifting processing speed and increase auditory-verbal short-term memory, neurotrophic levels and baroreceptor function. A response of the respiratory tract to oxidative stress was also noted. There is a need to rigorously examine the safety of normobaric therapy. Further studies should be carried out with physician examination, both pre and post treatment.

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Apoptosis inhibition is involved in improvement of sevoflurane-induced cognitive impairment following normobaric hyperoxia preconditioning in aged rats.

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Apoptosis inhibition is involved in improvement of sevoflurane-induced cognitive impairment following normobaric hyperoxia preconditioning in aged rats.

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