Propofol administration to the fetal–maternal unit reduces cardiac oxidative stress in preterm lambs subjected to prenatal asphyxia and cardiac arrest

Schumacher, Matthias; Houthuizen, Patrick; Collins, Jennifer J. P.; Zimmermann, Luc J. I.; Kramer, Boris W.

doi:10.1038/pr.2016.10

Cited by 4 publications

(2 citation statements)

References 41 publications

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“…Propofol did not affect physical development, and there were no significant differences in bodyweight or dyskinesia between propofol exposure and control groups. In late-pre-term lambs subjected to asphyxia, it has been shown that maternal propofol anaesthesia results in less cardiac injury than does isoflurane anaesthesia [49], and cardiac protection from prenatal asphyxia has also been observed [49,57]. This suggests that the learning and memory impairments observed in the current study were induced by maternal propofol exposure instead of physical differences.…”

Section: Discussionsupporting

confidence: 49%

Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF‐TrkB signalling pathway

Zhong

Luo

Zhao

et al. 2016

J Cellular Molecular Medi

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The brain‐derived neurotrophic factor (BDNF)‐tyrosine kinase B (TrkB) (BDNF‐TrkB) signalling pathway plays a crucial role in regulating learning and memory. Synaptophysin provides the structural basis for synaptic plasticity and depends on BDNF processing and subsequent TrkB signalling. Our previous studies demonstrated that maternal exposure to propofol during late stages of pregnancy impaired learning and memory in rat offspring. The purpose of this study is to investigate whether the BDNF‐TrkB signalling pathway is involved in propofol‐induced learning and memory impairments. Propofol was intravenously infused into pregnant rats for 4 hrs on gestational day 18 (E18). Thirty days after birth, learning and memory of offspring was assessed by the Morris water maze (MWM) test. After the MWM test, BDNF and TrkB transcript and protein levels were measured in rat offspring hippocampus tissues using real‐time PCR (RT‐PCR) and immunohistochemistry (IHC), respectively. The levels of phosphorylated‐TrkB (phospho‐TrkB) and synaptophysin were measured by western blot. It was discovered that maternal exposure to propofol on day E18 impaired spatial learning and memory of rat offspring, decreased mRNA and protein levels of BDNF and TrkB, and decreased the levels of both phospho‐TrkB and synaptophysin in the hippocampus. Furthermore, the TrkB agonist 7,8‐dihydroxyflavone (7,8‐DHF) reversed all of the observed changes. Treatment with 7,8‐DHF had no significant effects on the offspring that were not exposed to propofol. The results herein indicate that maternal exposure to propofol during the late stages of pregnancy impairs spatial learning and memory of offspring by disturbing the BDNF‐TrkB signalling pathway. The TrkB agonist 7,8‐DHF might be a potential therapy for learning and memory impairments induced by maternal propofol exposure.

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Section: Discussionsupporting

confidence: 49%

Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF‐TrkB signalling pathway

Zhong

Luo

Zhao

et al. 2016

J Cellular Molecular Medi

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“…The present findings suggest that isoflurane anesthesia has no influence on the MMP-2 activation in pregnancy, and moreover, such mechanism is involved during the remodeling period in healthy gestation since significant hemodynamic, vascular, and uteroplacental adaptations are needed for a proper blood supply during fetal developing [ 33 ]. Moreover, increases in the activity of 64 kDa MMP-2 in the Non-Preg+Iso group compared with the Non-Preg group may be explained by pro-oxidant effect of isoflurane anesthesia [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy

Souza,

Caetano,

Rodrigues

et al. 2024

Bioscience Reports

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Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n = 28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) vs 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.

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Propofol Prevents Hippocampal Neuronal Loss and Memory Impairment in Cerebral Ischemia Injury Through Promoting PTEN Degradation

Chen

et al. 2016

J Mol Neurosci

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Neuroprotective effect of propofol against cerebral ischemia injury was widely investigated. However, its mechanisms remain unclear. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is supposed as a cell survival pathway, and phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a negative regulator of AKT phosphorylation. Whether PTEN was involved in the protective effect of propofol against cerebral ischemia injury was not elucidated. In this study, the function of PTEN in the acute phase of cerebral ischemia injury was investigated. Our data showed that propofol promoted the PTEN degradation in the acute phase of cerebral ischemia injury and concurrently activated AKT phosphorylation. The increase of ubiquitinated PTEN caused by cerebral ischemia injury were degraded in propofol-pretreated rats. Moreover, we evidenced that proteasome activity was stimulated in propofol-treated rats. These data pointed that PTEN degradation was facilitated in the acute phase after propofol treatment possibly through activating ubiquitin-proteasome system. Therefore, we applied PTEN inhibitor-bpV before cerebral ischemia injury. Like propofol, bpV pretreatment also mitigated cerebral ischemia injury-induced cell loss in CA1 region and memory impairment. Taken together, our data suggest that PTEN degradation is neuroprotective against cerebral ischemia injury and propofol facilitates PTEN degradation to prevent hippocampal neuronal loss and memory deficit in cerebral ischemia injury.

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Propofol administration to the fetal–maternal unit reduces cardiac oxidative stress in preterm lambs subjected to prenatal asphyxia and cardiac arrest

Cited by 4 publications

References 41 publications

Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF‐TrkB signalling pathway

Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF‐TrkB signalling pathway

Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy

Propofol Prevents Hippocampal Neuronal Loss and Memory Impairment in Cerebral Ischemia Injury Through Promoting PTEN Degradation

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