The neurotoxic effect of isoflurane on age‐defined neurons generated from tertiary dentate matrix in mice

Xiao, Xinli; Wu, Jingtao; Zhang, Hanze; Wang, Yidi; Zhang, Jing‐Qiao; Liu, Lefan; Yuchen,; Minli,; Yang, Pengbo; Wu, Xiaolin; Liu, Jianxin

doi:10.1002/brb3.1949

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…The immunofluorescence images were analyzed as described previously. 18 The newborn neurons in the angular and dentate gyrus regions were counted in 6 slices in each group. To reduce the error rate, each sample was analyzed in 2 technical replicates and 6 biological replicates for each group.…”

Section: Immunofluorescencementioning

confidence: 99%

Alfaxalone Alleviates Neurotoxicity and Cognitive Impairment Induced by Isoflurane Anesthesia in Offspring Rats

Zhao

Guo

et al. 2023

Anesthesia &Amp; Analgesia

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BACKGROUND:The anesthetic isoflurane can cause neurotoxicity in fetuses and offspring of rats, affecting their neurodevelopment. However, the underlying mechanisms and therapeutic targets of isoflurane-induced neurotoxicity remain to be identified. Alfaxalone (ALF) is a steroid anesthetic. Steroids have been reported to have neuroprotective effects. This study aimed to investigate whether ALF could alleviate the isoflurane-induced neurotoxicity in fetuses and offspring of rats. METHODS: On gestation day 15 (G15), the pregnant SD rats were randomly assigned to 4 groups: control 1 (CTL1) + control 2 (CTL2), isoflurane (ISO) + CTL2, CTL1 + ALF, and ISO + ALF. To analyze the changes in the expression levels of inflammatory cytokines, apoptotic factors, and synaptophysin, the brain tissues from the G15 fetuses and offspring at postnatal day 7 (P7), postnatal day 14 (P14), and postnatal day 31 (P31) were collected. The newborn neurons in the rats' offspring at P7, P14, and P31 were counted using immunofluorescence techniques. The Morris water maze (MWM) test was performed to assess the learning and memory abilities of P31 offspring rats. RESULTS: ALF significantly alleviated the isoflurane-induced increase in the expression levels of inflammatory cytokines and apoptotic factors, such as interleukin (IL)-6 (ISO + CTL2 versus ISO + ALF: 5.133 ± 0.739 versus 1.093 ± 0.213, P < .001) and Caspase-3 (6.457 ± 0.6 versus 1.062 ± 0.1, P < .001) in the G15 fetuses. In P31 offspring rats, the expression levels of synaptophysin (0.719 ± 0.04 versus 1.068 ± 0.072, P < .001) and the number of newborn neurons in the dentate gyrus of the hippocampus were significantly lower in the ISO + CTL2 group as compared to those in the ISO + ALF group (118 ± 6 versus 140 ± 7, P < .001). These changes also occurred in the rat offspring at P7 and P14. In the MWM test, the escape latency of CTL1 + ALF group rats was significantly lower than that of ISO + ALF group rats (41 ± 6 versus 31 ± 7, P < .001) at P31. CONCLUSIONS: Based on these findings, this study suggested that isoflurane exposure during pregnancy in rats could cause neuroinflammation and death of embryos as well as impairment of cognitive function in the offspring rats. ALF can be used to counteract the negative effects of isoflurane. (Anesth Analg 2023;136:1206-16) KEY POINTS• Question: Are there any effects of alfaxalone (ALF) on the neuroinflammation and apoptosis during pregnancy in fetal rats and on the impairment of cognitive function in the offspring rats after isoflurane anesthesia? • Findings: ALF could reduce the effects of isoflurane by reducing neuroinflammation and apoptosis. • Meaning: ALF might reduce the isoflurane-induced neurotoxicity during brain development and alleviate the isoflurane-induced impairment of cognitive function.

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Section: Immunofluorescencementioning

confidence: 99%

Alfaxalone Alleviates Neurotoxicity and Cognitive Impairment Induced by Isoflurane Anesthesia in Offspring Rats

Zhao

Guo

et al. 2023

Anesthesia &Amp; Analgesia

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“…The results of the present study are expressed as the mean ± SEM. At the end of the study period, the mice were sacrificed using isoflurane 2% inhalation 1 liter/minute for >4 h following a procedure described elsewhere with a modification of the dose (18). Animal death was verified by the absence of respiration and heartbeat for a period of >5 min.…”

Section: Stz [Chemical Name 2-deoxy-2-(3-(methyl-3-nitrosourea)-d -Gl...mentioning

confidence: 99%

Stigmasterol isolated from the ethyl acetate fraction of Morinda citrifolia fruit (using the bioactivity‑guided method) inhibits α‑amylase activity: In vitro and in vivo analyses

Lolok,

Sumiwi,

Sahidin

et al. 2023

World Acad Sci J

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Stigmasterol, a bioactive phytosterol that is present in numerous plants, has been explored for its antidiabetic activity. The present study extracted, fractionated, isolated and characterized the isolate in the ethyl acetate fraction of Morinda citrifolia fruit and investigated its potency as an inhibitor of α-amylase. The bioactivity-guided antidiabetic assay revealed that all fractions (A-G) exhibited notable differences with the negative control. However, fraction C reduced blood sugar levels in Swiss-Webster male mice with streptozotocin-induced diabetes by 43.08%, and was further purified to obtain the isolate. The chemical structure of the isolate was determined by employing proton nuclear magnetic resonance (NMR), carbon-13 NMR, distortionless enhancement by polarization transfer and liquid chromatography-mass spectrometry, and was confirmed as stigmasterol. An in vitro assay revealed that stigmasterol exhibited potent inhibitory activity against human α-amylase activity with an IC 50 value of 10.29±0.76 µg/ml, compared to that of the fruit extract and acarbose, which were 14.16±5.72 and 43.37±1.56 µg/ml, respectively. On the whole, the present study demonstrates that both Morinda citrifolia fruit extract and stigmasterol isolated from the ethyl acetate fraction of the fruit may have the potential to be developed as an anti-diabetic drugs due to their inhibitory effects on α-amylase activity. However, further studies are required to guarantee its efficacy and safety for humans.

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“…Neurotoxicity mechanisms of inhalation anaesthetics[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] …”

mentioning

confidence: 99%

Negative effect of general anesthesia on the human brain - mechanism and methods of prevention

Dembowska,

Dubaj,

Bigosiński

et al. 2023

J Pre Clin Clin Res.

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Introduction andObjective. General anesthesia is an integral part of many medical procedures. Its main premise is that it is completely reversible and has no effect on the human brain. Unfortunately, a number of scientific findings report potential effects of anaesthetics on the human nervous system. The aim of this review is to present the negative impact of sevoflurane (inhalation anaesthetic) and propofol (intravenous anaesthetic) on the human brain with an analysis of its mechanisms and factors, and possible methods of preventing this phenomenon. Review Methods. A review was undertaken of the most current literature using PubMed and Google Scholar databases, on the mechanism of action and the negative effects of sevoflurane and propofol on the brain and methods of its prevention. Included are both original works, reviews and case reports from Poland and worldwide. Brief description of the state of knowledge. Post-operative cognitive dysfunction affects 10-65% of patients. Sevoflurane and propofol have potentially damaging effects on the human brain. This occurs mainly through induction of neuronal cell apoptosis and disruption of synaprogenesis by affecting receptor proteins, cell organelles (mitochondria, endoplasmic reituclum) and signaling pathways (apoptotic and trophic) of neurons. However, this effect depends on the drug dose and patient-dependent factors (age, diseases, cognitive status before anaesthesia). Summary. Anaesthetics have potentially harmful effects on the human brain, although only in large and repeated doses. One should also not forget the much more notable effect of mechanical damage to tissues during surgery. In order to prevent cognitive dysfunction, both a detailed preoperative assessment of the patient's condition and the use of additional pharmacological and non-pharmacological measures during surgery are important.

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The neurotoxic effect of isoflurane on age‐defined neurons generated from tertiary dentate matrix in mice

Abstract: The safety of anesthetics has been questioned since accumulating evidences from rodents and nonhuman primates have indicated that anesthetics exposure, especially in the young brain, might result in subsequent neurobehavioral abnormalities including cognitive

Cited by 5 publications

References 27 publications

Alfaxalone Alleviates Neurotoxicity and Cognitive Impairment Induced by Isoflurane Anesthesia in Offspring Rats

Alfaxalone Alleviates Neurotoxicity and Cognitive Impairment Induced by Isoflurane Anesthesia in Offspring Rats

Stigmasterol isolated from the ethyl acetate fraction of Morinda citrifolia fruit (using the bioactivity‑guided method) inhibits α‑amylase activity: In vitro and in vivo analyses

Negative effect of general anesthesia on the human brain - mechanism and methods of prevention

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