254 research outputs found
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The potential dual effects of sevoflurane on AKT/GSK3β signaling pathway
Background: Anesthesia with multiple exposures of commonly used inhalation anesthetic sevoflurane induces neuroinflammation and cognitive impairment in young mice, but anesthesia with a single exposure to sevoflurane does not. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway is involved in neurotoxicity and neurobehavioral deficits. However, whether sevoflurane can induce a dual effect (increase versus decrease) on the activation of AKT/GSK3β signaling pathway remains to be determined. We therefore set out to assess the effects of sevoflurane on AKT/GSK3β signaling pathway in vivo and in vitro. Methods: Six day-old wild-type mice were exposed to 3% sevoflurane two hours daily for one or three days. In the in vitro studies, H4 human neuroglioma cells were treated with 4% sevoflurane for two or six hours. We then determined the effects of different sevoflurane treatments on the levels of phosphorylated (P)-GSK3β(ser9) and P-AKT(ser473) by using Western blot analysis. Results: Here we show that anesthesia with 3% sevoflurane two hours daily for one day increased the levels of P-GSK3β(ser9) and P-AKT(ser473), but the anesthesia with 3% sevoflurane daily for three days decreased them in the mice. The treatment with 4% sevoflurane for two hours increased, but the treatment with 4% sevoflurane for six hours decreased, the levels of P-GSK3β(ser9) and P-AKT(ser473) in the H4 human neuroglioma cells. Conclusions: Anesthetic sevoflurane might induce a dual effect (increase versus decrease) on the activation of the AKT/GSK3β signaling pathway. These studies have established a system to perform further studies to determine the effects of sevoflurane on brain function
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Chronic treatment with anesthetic propofol attenuates β-amyloid protein levels in brain tissues of aged mice
Alzheimer’s disease (AD) is the most common form of dementia. At the present time, however, AD still lacks effective treatments. Our recent studies showed that chronic treatment with anesthetic propofol attenuated brain caspase-3 activation and improved cognitive function in aged mice. Accumulation of β-amyloid protein (Aβ) is a major component of the neuropathogenesis of AD dementia and cognitive impairment. We therefore set out to determine the effects of chronic treatment with propofol on Aβ levels in brain tissues of aged mice. Propofol (50 mg/kg) was administrated to aged (18 month-old) wild-type mice once a week for 8 weeks. The brain tissues of mice were harvested one day after the final propofol treatment. The harvested brain tissues were then subjected to enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Here we report that the propofol treatment reduced Aβ (Aβ40 and Aβ42) levels in the brain tissues of the aged mice. Moreover, the propofol treatment decreased the levels of β-site amyloid precursor protein cleaving enzyme (the enzyme for Aβ generation), and increased the levels of neprilysin (the enzyme for Aβ degradation) in the brain tissues of the aged mice. These results suggested that the chronic treatment with propofol might reduce brain Aβ levels potentially via decreasing brain levels of β-site amyloid precursor protein cleaving enzyme, thus decreasing Aβ generation; and via increasing brain neprilysin levels, thus increasing Aβ degradation. These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research
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Using the Chinese version of Memorial Delirium Assessment Scale to describe postoperative delirium after hip surgery
Objective:: Memorial Delirium Assessment Scale (MDAS) assesses severity of delirium. However, whether the MDAS can be used in a Chinese population is unknown. Moreover, the optimal postoperative MDAS cutoff point for describing postoperative delirium in Chinese remains largely to be determined. We therefore performed a pilot study to validate MDAS in the Chinese language and to determine the optimal postoperative MDAS cutoff point for delirium. Methods:: Eighty-two patients (80 ± 6 years, 21.9% male), who had hip surgery under general anesthesia, were enrolled. The Confusion Assessment Method (CAM) and Mini-Mental State Examination (MMSE) were administered to the patients before surgery. The CAM and MDAS were performed on the patients on the first, second and fourth postoperative days. The reliability and validity of the MDAS were determined. A receiver operating characteristic (ROC) curve was used to determine the optimal Chinese version MDAS cutoff point for the identification of delirium. Results:: The Chinese version of the MDAS had satisfactory internal consistency (α = 0.910). ROC analysis obtained an average optimal MDAS cutoff point of 7.5 in describing the CAM-defined postoperative delirium, with an area under the ROC of 0.990 (95% CI 0.977–1.000, P < 0.001). Conclusions:: The Chinese version of the MDAS had good reliability and validity. The patients whose postoperative Chinese version MDAS cutoff point score was 7.5 would likely have postoperative delirium. These results have established a system for a larger scale study in the future
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Preoperative cerebrospinal fluid β-Amyloid/Tau ratio and postoperative delirium
Objective: The neuropathogenesis of postoperative delirium remains unknown. Low cerebrospinal fluid (CSF) β-amyloid protein (Aβ) and high CSF Tau levels are associated with Alzheimer's disease. We, therefore, assessed whether lower preoperative CSF Aβ/Tau ratio was associated with higher incidence and greater severity of postoperative delirium. Methods: One hundred and fifty-three participants (71 ± 5 years, 53% men) who had total hip/knee replacement under spinal anesthesia were enrolled. CSF was obtained during initiation of spinal anesthesia. The incidence and severity of postoperative delirium were determined by Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS) on postoperative day 1 and 2. Aβ40, Aβ42, and Tau levels in the CSF were measured by enzyme-linked immunosorbent assay. The relationships among these variables were determined, adjusting for age and gender. Results: Participants in the lowest quartile of preoperative CSF Aβ40/Tau and Aβ42/Tau ratio had higher incidence (32% vs. 17%, P = 0.0482) and greater symptom severity of postoperative delirium (Aβ40/Tau ratio: 4 vs. 3, P = 0.034; Aβ42/Tau ratio: 4 vs. 3, P = 0.062, the median of the highest MDAS score) as compared to the combination of the rest of the quartiles. The preoperative CSF Aβ40/Tau or Aβ42/Tau ratio was inversely associated with MDAS score (Aβ40/Tau ratio: −0.12 ± 0.05, P = 0.014, adj. −0.12 ± 0.05, P = 0.018; Aβ42/Tau ratio: −0.65 ± 0.26, P = 0.013, adj. −0.62 ± 0.27, P = 0.022). Interpretation Lower CSF Aβ/Tau ratio could be associated with postoperative delirium, pending confirmation of our preliminary results in further studies. These findings suggest potential roles of Aβ and/or Tau in postoperative delirium neuropathogenesis
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