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. 2024 Dec 20;13(6):tfae220. doi: 10.1093/toxres/tfae220

Downregulation of circTLK1 improves the impairments in learning and memory induced by anesthetics via regulating miR-374b-5p expression and reducing neuroinflammation

Xiaoli Zhu 1,✉
PMCID: PMC11659641  PMID: 39712639

Abstract

Background: Sevoflurane (Sev) is a common anesthetic used during surgery, but research on its induction of neurotoxicity and learning memory impairment is insufficient. This study aimed to explore the role of Circular RNA tousled like kinase 1 (circTLK1) and its target microRNA (miR)-374b-5p in Sev-induced neurotoxicity and learning memory impairment. Methods: Mouse hippocampal neuronal HT22 cells and SD rats were treated with Sev. Levels of circTLK1 and miR-374b-5p were detected using RT-qPCR. The concentration of inflammatory factors was determined using ELISA. Cell viability and apoptosis were analyzed using CCK-8 and flow cytometry. Targeting relationship between circTLK1 and miR-374b-5p was validated using dual-luciferase reporter assays and RIP experiments. The Morris water maze test was used to assess the learning and spatial memory abilities of rats. Results: The results indicated that Sev treatment stimulated neuroinflammation and oxidative stress while increasing circTLK1 levels and decreasing miR-374b-5p levels in both rats and HT22 cells. Silencing circTLK1 alleviated the decrease in cell viability, increased apoptosis rates, and raised concentrations of inflammatory factors caused by Sev treatment. In in vivo experiments, silencing circTLK1 was also found to counteract the oxidative stress, neuroinflammation, and learning and memory impairment induced by Sev treatment in rats. Additionally, circTLK1 was shown to interact with miR-374b-5p, and inhibiting miR-374b-5p could counteract the neuroprotective effects of si-circTLK1. Conclusion: This research suggested that silencing circTLK1 can mitigate Sev-induced neurotoxicity and learning memory impairment by modulating miR-374b-5p.

Keywords: circTLK1, miR-374b-5p, sevoflurane, neurotoxicity

1 Introduction

Sevoflurane (Sev) is a low-fat soluble inhalation anesthetic that has been used for over 30 years.1 It is widely used in many countries due to its fast induction and recovery, low blood/gas partition coefficient, and rapid metabolism.2 Studies have shown that Sev treatment can suppress myocardial cell ischemia–reperfusion injury,3 but it has also been associated with inducing neuroinflammation and cognitive impairment.4 Research on elderly mice exposed to Sev has shown cognitive decline,5 and Sev can induce neuroinflammation through various pathways.6 The mechanisms of neurotoxicity caused by Sev and learning, and memory dysfunction are not completely understood, especially considering its common use as a general anesthetic, particularly in pediatric surgeries.7 Therefore, research on the neurotoxicity of Sev is crucial.

Circular RNAs (circRNAs) have a unique circular structure and play a role in various physiological processes by interacting with miRNAs. circRNAs are abundant in mammalian neuronal tissues and are involved in brain development, aging, and several neurological diseases.8 Several circRNAs have strong associations with Alzheimer's disease.9 Among these, Circular RNA tousled like kinase 1 (circTLK1) is less studied but knocking out circTLK1 has been shown to inhibit cardiomyocyte apoptosis10 and alleviate Myocardial ischemia/reperfusion injury.11 Notably, high levels of circTLK1 can exacerbate neuronal damage and functional impairment post-ischemic stroke, while reducing circTLK1 levels can alleviate neuron damage and improve long-term neurological deficits.12 However, the role of circTLK1 in Sev-induced neurotoxicity is not well understood Numerous studies have shown that circRNAs can function by binding to miRNA targets. In our initial analysis, we predicted that circTLK1 could target miR-374b-5p based on the database, and miR-374b-5p has the ability to enhance neuronal viability and attenuate neuroinflammation.13

Given the significant roles of Sev, circTLK1, and miR-374b-5p in neuronal damage and cellular inflammation, this study analyzed the levels of circTLK1 and miR-374b-5p in Sev-induced neuronal cells, as well as their regulatory relationship. Functional gain or loss experiments were conducted to validate the roles of circTLK1 and miR-374b-5p on neuronal cell viability. Additionally, animal behavioral experiments were included to uncover the role and mechanism of circTLK1 in neuronal inflammation and anesthesia-induced learning and memory dysfunction.

2 Materials and methods

2.1 Cell culture

Mouse hippocampal neuronal cell line HT22 was cultured in DMEM medium supplemented with 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin. The culture conditions included 5% CO2 at 37 °C.

2.2 Sev treatment

HT22 cells were exposed to a mixture of air containing 1%, 2%, 4% Sev, and 5% CO2 in a sealed chamber. The Sev concentration inside the chamber was monitored by a Datex TM Infrared Analyzer. The control group was exposed to air containing 5% CO2. After 6 h of culturing under these conditions, HT22 cells were transferred to a culture chamber at 37 °C, 5% CO2 for an additional 24 h. The Sev and other groups requiring Sev treatment were cultured in an environment of 4% Sev and 5% CO2 mixed air for 6 h.

2.3 Cell transfection

When HT22 cells reached the logarithmic phase, they were seeded into a 6-well plate for transfection. Using Lipofectamine 3,000 as per the instructions, cells were transfected with circTLK1 siRNA (si-circTLK1), siRNA negative control (si-NC), miR-374b-5p mimic, mimic negative control (NC), miR-374b-5p inhibitor, or inhibitor negative control (NC) and incubated for 48 h.

2.4 RNA extraction and RT-qPCR

Total RNA from HT22 cells and rat hippocampal tissue was extracted using TRIzol reagent according to the instructions. The extracted circTLK1 and miR-374b-5p were reverse transcribed into cDNA, followed by RT-qPCR using TB Green Fast qPCR mix kit or miRcute Plus miRNA qPCR kit with SYBR Green I. β-actin and U6 were used as internal controls, and the expression levels of circTLK1 and miR-374b-5p were calculated using the 2-ΔΔCt method. The primers used were as follows: circTLK1, 5'-CAGTCAATGGAGCAGAGAA-3′ (forward) and 5'-CCATTCTTGTTGCCTTTTTG-3′ (reverse). miR-374b-5p， 5'-CGGATTAGGCACTGTGAATAC AAAG-3′(forward and 5'-TCTGCCAGGTAGAGTGGGAAAC-3′(reverse). β-actin， 5'-AGAAAATCTGGCACCACACC-3′ (forward) and 5'-CCATCTCTTGCTCGAAGTCC-3′ (reverse). U6， 5'-CTCGCTTCGGCAGCACA-3′ (forward) and 5'-AACGCTTCACGAATTTGCGT-3′ (reverse).

2.5 Enzyme-linked immunosorbent assay (ELISA)

After centrifugation of homogenized HT22 cells and rat hippocampal tissue, the concentrations of inflammatory factors including IL-6, IL-1β, and TNF-α in the supernatant were measured using commercial ELISA kits.

2.6 Cell viability

Transfected cells were cultured for 48 h and then seeded at a density of 5 × 103 in a 96-well plate. CCK-8 reagent was added to the wells and the OD value at 450 nm was determined using a microplate reader after 0, 24, 48 and 72 h of incubation, respectively.

2.7 Cell apoptosis

Following a wash with PBS, HT22 cells were resuspended in 1 × binding buffer and stained with Annexin V-FITC and PI. After a 5 min incubation, cell apoptosis was analyzed using a flow cytometer.

2.8 LDH, SOD, and MDA assay

After the experiment, hippocampal tissues from rats and HT22 cells were collected, homogenized, and the supernatant was collected after centrifugation. Using the corresponding kits such as LDH cytotoxicity assay kit, LDH, SOD, and MDA levels in the samples were measured according to the instructions.

2.9 Dual-luciferase reporter assay

The circTLK1 sequence was cloned into the pmirGLO vector to construct wild-type circTLK1-WT and mutant recombinant plasmid circTLK1-MT. After transfection of these plasmids along with miR-374b-5p mimic, mimic NC, miR-374b-5p inhibitor, or inhibitor NC into HT22 cells, luciferase activity was measured 48 h later.

2.10 RNA immunoprecipitation (RIP) assay

The RIP assay was conducted to verify the binding of circTLK1 and miR-374b-5p. The Magna RIP kit was used according to the instructions. The antibodies used in the experiment were anti-Ago2 and anti-IgG. Total RNA was extracted and purified from HT22 cells using TRIzol, and the enrichment of circTLK1 and miR-374b-5p was detected by RT-qPCR.

2.11 Nuclear and cytoplasmic RNA fraction isolations

According to the instructions, the A SurePrep Nuclear or Cytoplasmic RNA Purification Kit was used to separate and collect RNA from the nuclei and cytoplasm of HT22 cells to analyze the subcellular localization of circTLK1 in HT22 cells. RT-qPCR was used to detect the expression of circTLK1 in the cytoplasm and nucleus. GAPDH and U2 were used as controls for the cytoplasm and nucleus, respectively.

2.12 Animal grouping

Prior approval from author's institution was obtained for the experiment. Thirty SPF male SD rats (18 months old) were purchased from Beijing Vitonglihua Experimental Animal Technology Co. After acclimating for 7 days, rats were randomly divided into 6 groups, each comprising 5 rats: untreated group (control), Sev treatment group, Sev + si-circTLK1 group, Sev + si-NC group, Sev + si-circTLK1 + miR-374b-5p antagomir group, and Sev + si-circTLK1 + antagomir NC group. The transfection reagents were injected bilaterally into the rat hippocampal region. Apart from the untreated group, rats in the other groups were transfected with reagents and treated with 2.5% Sev daily for 6 h, continuously for one week. The rats did not die during the experiment and were euthanized after the experiment and hippocampal tissue was collected for analysis.

2.13 Morris water maze test

The Morris water maze Test was conducted to evaluate the learning and spatial memory abilities of the rats. The maze consisted of a circular water pool with a diameter of 180 cm and a depth of 80 cm, filled with opaque, warm water (22 ± 2 °C). The pool was divided into four quadrants, each with distinct visual cues, and a circular platform (10 cm in diameter) was placed submerged 2 cm below the water surface in one quadrant. Prior to the formal experiment, the rats were acclimated to the water pool environment. Subsequently, a 5-day spatial navigation test was conducted, where the rats were placed in the water from semi-random quadrants, and the time taken for them to find the platform was recorded as the escape latency. If a rat did not find the platform within 60s, it was guided to the platform location by the experimenter, and the escape latency was recorded as 60s. On the 6th day, a probe trial was conducted where the platform was removed, and the rats were allowed to freely swim for 90s. The time spent in the target quadrant and the number of crossings over the platform location were recorded.

2.14 Statistical analysis

SPSS 23.0 software and GraphPad Prism 9.0 were used for data analysis. Mean ± SD was employed to describe all data at least three replications. T-test was used for comparison between two groups, and One-way ANOVA followed by post-hoc Tukey’s test was applied between multiple groups. P < 0.05 was considered to indicate a statistically significant difference.

3 Results

3.1 Sev affected cell viability and increased the expression of circTLK1 while inhibiting miR-374b-5p expression.

As shown in Fig. 1A and B, the viability of HT22 cells was significantly affected by Sev treatment, with higher Sev concentrations resulting in lower cell viability. Additionally, cell viability decreased with prolonged exposure to 4% Sev treatment (P < 0.01). The study also found that circTLK1 levels significantly increased in Sev-treated cells, while miR-374b-5p levels decreased significantly, and this trend intensified with increasing Sev concentrations (P < 0.001, Fig. 1C and D).

Fig. 1.

Fig. 1

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circTLK1 was highly expressed in Sev-induced HT22 cells, miR-374b-5p was significantly downregulated. A. Cell viability decreased with increasing concentration of Sev induction. B. Cell viability significantly decreased with increasing time of induction with 4% Sev. C.circTLK1 levels increased with increasing Sev treatment concentration. D. miR-374b-5p levels decreased with increasing Sev treatment concentration.

3.2 circTLK1 targeted miR-374b-5p

Cellular sublocalization analysis, as shown in Fig. 2A, indicated that circTLK1 was mainly localized in the cytoplasm. Dual-luciferase reporter experiments demonstrated that miR-374b-5p mimic inhibited the luciferase activity of the circTLK1-WT vector (P < 0.001), while circTLK1-MT was not affected by the miR-374b-5p mimic (Fig. 2C), and binding sites existed between circTLK1 and miR-374b-5p (Fig. 2B). RIP experiments further validated the targeted binding relationship between circTLK1 and miR-374b-5p (Fig. 2D). Sev treatment significantly decreased miR-374b-5p levels, whereas transfection of si-circTLK1 significantly increased miR-374b-5p levels (P < 0.001, Fig. 2E). These results collectively indicated the targeted binding between circTLK1 and miR-374b-5p.

Fig. 2.

Fig. 2

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circTLK1 targeted miR-374b-5p. A. Subcellular localization analysis of circTLK1. B. Binding sites of circTLK1 and miR-374b-5p. C. Dual luciferase reporter assay. D. RIP assay. E. si-circTLK1 can promote the expression of miR-374b-5p.

3.3 Involvement of circTLK1/miR-374b-5p in Sev-treated HT22 cells

RT-qPCR results demonstrated that the expression of circTLK1 increased under the influence of Sev, while it was downregulated in cells transfected with si-circTLK1 (P < 0.001, Fig. 3A). As depicted in Fig. 3B, silencing circTLK1 led to an increase in miR-374b-5p levels (P < 0.001). Treatment with Sev decreased the viability of HT22 cells, and silencing circTLK1 alleviated the inhibitory effect of Sev on cell viability, while transfection of miR-374b-5p inhibitor counteracted the impact of si-circTLK1 on cell viability (P < 0.01, Fig. 3C). The trends of these factors on the apoptosis rate of HT22 cells were reversed (P < 0.01, Fig. 3D). Furthermore, ELISA analysis revealed that the changes in TNF-α, IL-6, and IL-1β concentrations aligned with the trends in apoptosis rate changes (P < 0.01, Fig. 3E). LDH and MDA concentrations showed similar changes (P < 0.01, Fig. 3F and G), while SOD levels exhibited opposite changes (P < 0.01, Fig. 3H).

Fig. 3.

Fig. 3

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The role of circTLK1/miR-374b-5p in Sev-treated HT22 cells. A. Regulation of circTLK1 and miR-374b-5p on circTLK1 levels. B. And miR-374b-5p levels. C. And cell viability. D. And cell apoptosis. E. And cell inflammatory factors. F. And LDH. G. And MDA. H. And SOD.

3.4 Influence of circTLK1/miR-374b-5p on Sev-induced cognitive deficits

As shown in Fig. 4A, in hippocampal tissues of rats treated with Sev, circTLK1 levels increased, but they decreased after transfection with si-circTLK1 (P < 0.001). However, Sev treatment led to a reduction in miR-374b-5p levels in hippocampal tissues, and miR-374b-5p antagomir inhibited miR-374b-5p expression. Following si-circTLK1 transfection, miR-374b-5p levels were restored (P < 0.01, Fig. 4B). Post Sev treatment, rats exhibited increased escape latency, while the number of platform crossings and time spent in the target quadrant significantly decreased (P < 0.001, Fig. 4C–E). Transfection with si-circTLK1 mitigated behavioral changes induced by Sev treatment (P < 0.001, Fig. 4C–E). Simultaneously, transfection with miR-374b-5p antagomir eliminated the protective effect of si-circTLK1 on rat learning and memory (P < 0.01, Fig. 4C–E).

Fig. 4.

Fig. 4

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The role of circTLK1/miR-374b-5p in Sev-induced learning and memory impairments. A. circTLK1 levels after regulating circTLK1 and miR-374b-5p. B. And miR-374b-5p levels. C. MWM test to analyze latency time D. And the number of platform crossings. F. And time in the target quadrant.

3.5 Effect of circTLK1/miR-374b-5p on neuroinflammation and oxidative stress induced by Sev

ELISA results demonstrated that compared to the control group, Sev treatment increased TNF-α, IL-6, and IL-1β levels in rat serum, and transfection with si-circTLK1 inhibited the elevated levels of these inflammatory factors induced by Sev (P < 0.001), while miR-374b-5p antagomir counteracted the inhibitory effect of si-circTLK1 (P < 0.05, Fig. 5A). As shown in Fig. 5B–D, Sev treatment induced the production of LDH and MDA in rats and reduced SOD concentration. However, transfection with si-circTLK1 mitigated the impact of Sev on oxidative stress. Conversely, transfection with miR-374b-5p antagomir hindered the protective effect of si-circTLK1 (P < 0.05, Fig. 5B–D).

Fig. 5.

Fig. 5

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The effects of circTLK1/miR-374b-5p on Sev-induced rat neuroinflammation and oxidative stress. A. Effects of circTLK1/miR-374b-5p on inflammatory factors in rat hippocampus. B. And LDH. C. And MDA. D. And SOD.

4 Discussion

Due to the widespread use of Sev in various surgeries, the impact of Sev exposure on the human body has been increasingly emphasized. There were conflicting views on the effects of Sev on the body. Some studies found that Sev had neuroprotective effects, such as alleviating brain damage after subarachnoid hemorrhage (SAH).14 However, other studies indicated that patients receiving Sev anesthesia had a certain probability of developing postoperative cognitive dysfunction (POCD),15 impairing patients' memory, attention, and cognitive abilities. Furthermore, Sev exposure was closely related to various neurodegenerative diseases, such as Alzheimer's disease (ad).16 The specific mechanism by which Sev induced learning and cognitive impairments was not fully understood, but it was generally believed that Sev could promote neuronal cell apoptosis17,18 and trigger neuroinflammation.19 Our study also demonstrated that Sev treatment led to decreased viability and increased apoptosis in HT22 cells, and Sev-treated rats exhibited cognitive impairments, which aligned with the findings of Qin et al.20

It is known that circular RNAs (circRNAs) are a type of non-coding RNA, with many circRNAs enriched in the brain compared to other tissues, and they may regulate synaptic activity.21 Our study introduced circTLK1, with past research showing that knocking out circTLK1 could alleviate inflammation and reduce apoptosis in brain injuries.22 Qiu et al. also found that inhibiting CircTLK1 expression could block the AKT/NF-κB pathway, reducing inflammation and oxidative stress induced by high glucose.23 Our research results indicated abnormal expression of circTLK1 in Sev-treated HT22 cells, and silencing circTLK1 could also alleviate Sev-induced neurotoxicity and oxidative stress, with an improvement in cognitive abilities of rats in the Morris water maze test. Chen et al. also reached similar conclusions, suggesting that circTLK1 could inhibit apoptosis and cytotoxicity, and alleviate dopamine neuronal damage in vivo and in vitro.24 Sev might induce neuronal cell damage by regulating circTLK1, as circRNA often acts as “microRNA sponges”, so we also analyzed the target miRNAs of circTLK1.

Through bioinformatics methods, we discovered that miR-374b-5p was a target miRNA of circTLK1, and we confirmed this conclusion using dual luciferase reporter assays and RIP experiments. Previous studies found that miR-374b-5p was often dysregulated in the process of cancer development.25,26 Additionally, miR-374b-5p was considered a potential biomarker for the diagnosis of Parkinson's disease.27 Some studies revealed that Sev significantly decreased the expression of miR-374b-5p and affected ischemia–reperfusion injury.28 Our research also confirmed that Sev treatment inhibited the expression of miR-374b-5p in HT22 cells. Transfection with si-circTLK1 could increase the level of miR-374b-5p, leading to improved cell viability, reduced apoptosis, decreased inflammation, and oxidative stress in vitro and in vivo. These findings were consistent with those of Zhang et al.13 However, other studies suggested that downregulating miR-374b-5p in nucleus pulposus (NP) cells could improve the inflammatory response induced by lipopolysaccharide in marrow cells,29 which might be due to differences in cell types and physiological processes.

Our research revealed the role of circTLK1 in Sev-induced neural injury, a finding that is significant for understanding the complex mechanisms of anesthetics in the human body. Although Sev is a widely used inhalational anesthetic that has demonstrated good safety and efficacy in several clinical applications,30 its potential effects on the nervous system, particularly with prolonged exposure or high-dose use, remain a topic of concern. While previous studies have confirmed its cardioprotective effects,31 the balance between Sev's protective effects and potential damage is particularly critical. Meanwhile, our results indicated that circTLK1 might act as a “sponge” for miR-374b-5p to influence gene expression, thereby exerting protective effects in Sev-induced neural injury. This finding offers a new perspective for alleviating the neural damage effects of Sev. Future research focused on developing or screening drugs that specifically silence circTLK1 and combining them with Sev anesthetic agents could potentially reduce neural damage and promote the recovery of neural function. In summary, our research provides new insights into understanding Sev's neural effects and presents potential targets for the future development of safer and more effective anesthetic drugs. However, our study also has certain limitations, and the next research focus will be on the downstream targets and signaling pathways of the circTLK1/miR-374b-5p axis, aiming to advance the development and clinical application of circRNA-regulated drugs and novel neuroprotective therapies.

In conclusion, Sev exposure stimulated neuroinflammation and oxidative stress, leading to learning and cognitive impairment. Silencing circTLK1 can inhibit Sev-induced neurotoxicity and cognitive deficits by regulating its target miR-374b-5p.

Acknowledgments

Not applicable.

Author contribution

X.Z. conducted the experiment, analyzed the data, wrote the manuscript, revised the manuscript.

Funding

No funding was received to assist with the preparation of this work.

Conflict of interest statement: There is no conflict of interest in this study.

References

  • 1. Kubota Y. Comparative study of sevoflurane with other inhalation agents. Anesth Prog. 1992:39(4–5):118–124. [PMC free article] [PubMed] [Google Scholar]
  • 2. Li M, Guo J, Wang H, Li Y. Involvement of mitochondrial dynamics and Mitophagy in Sevoflurane-induced cell toxicity. Oxidative Med Cell Longev. 2021:2021(1):6685468. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • 3. Sheng H, Xiong J, Yang D. Protective effect of Sevoflurane preconditioning on Cardiomyocytes against hypoxia/Reoxygenation injury by modulating iron homeostasis and Ferroptosis. Cardiovasc Toxicol. 2023:23(2):86–92. [DOI] [PubMed] [Google Scholar]
  • 4. Luo Y, Liu J, Hong Y, Peng S, Meng S. Sevoflurane-induced hypotension causes cognitive dysfunction and hippocampal inflammation in mice. Behav Brain Res. 2023:455:114672. [DOI] [PubMed] [Google Scholar]
  • 5. Fei X, Wang JX, Wu Y, Dong N, Sheng ZY. Sevoflurane-induced cognitive decline in aged mice: involvement of toll-like receptors 4. Brain Res Bull. 2020:165:23–29. [DOI] [PubMed] [Google Scholar]
  • 6. Joe Y-E, Jun JH, Oh JE, Lee J-R. Damage-associated molecular patterns as a mechanism of sevoflurane-induced neuroinflammation in neonatal rodents. Korean J Anesthesiol. 2024:77(4):468–479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Apai C, Shah R, Pandya TK, Shah S. Anesthesia and the developing brain: a review of Sevoflurane-induced neurotoxicity in Pediatric populations. Clin Ther. 2021:43(4):762–778. [DOI] [PubMed] [Google Scholar]
  • 8. Zhou M, Li S, Huang C. Physiological and pathological functions of circular RNAs in the nervous system. Neural Regen Res. 2024:19(2):342–349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Puri S, Hu J, Sun Z, Lin M, Stein TD, Farrer LA, et al. Identification of circRNAs linked to Alzheimer's disease and related dementias. Alzheimers Dement. 2023:19(8):3389–3405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Qiu Y, Yu Y, Qin XM, Jiang T, Tan YF, Ouyang WX, Xiao ZH, Li SJ. CircTLK1 modulates sepsis-induced cardiomyocyte apoptosis via enhancing PARP1/HMGB1 axis-mediated mitochondrial DNA damage by sponging miR-17-5p. J Cell Mol Med. 2021:25(17):8244–8260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Song YF, Zhao L, Wang BC, Sun JJ, Hu JL, Zhu XL, Zhao J, Zheng DK, Ge ZW. The circular RNA TLK1 exacerbates myocardial ischemia/reperfusion injury via targeting miR-214/RIPK1 through TNF signaling pathway. Free Radic Biol Med. 2020:155:69–80. [DOI] [PubMed] [Google Scholar]
  • 12. Wu F, Han B, Wu S, Yang L, Leng S, Li M, Liao J, Wang G, Ye Q, Zhang Y, et al. Circular RNA TLK1 aggravates neuronal injury and neurological deficits after ischemic stroke via miR-335-3p/TIPARP. J Neurosci. 2019:39(37):7369–7393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Zhang J, Wang R. Deregulated lncRNA MAGI2-AS3 in Alzheimer's disease attenuates amyloid-beta induced neurotoxicity and neuroinflammation by sponging miR-374b-5p. Exp Gerontol. 2021:144:111180. [DOI] [PubMed] [Google Scholar]
  • 14. Xing W, Zhao J, Liu J, Liu Z, Chen G. The protective effects of sevoflurane on subarachnoid hemorrhage. Med Gas Res. 2024:14(1):1–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Ding J, Zhang K, Wang D, Wang Q. Sevoflurane augments neuroinflammation by regulating DUSP6 via YTHDF1 in postoperative cognitive dysfunction. Toxicol Res (Camb). 2024:13(4):tfae100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Jiang J, Jiang H. Effect of the inhaled anesthetics isoflurane, sevoflurane and desflurane on the neuropathogenesis of Alzheimer's disease (review). Mol Med Rep. 2015:12(1):3–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Iketani M, Hatomi M, Fujita Y, Watanabe N, Ito M, Kawaguchi H, Ohsawa I. Inhalation of hydrogen gas mitigates sevoflurane-induced neuronal apoptosis in the neonatal cortex and is associated with changes in protein phosphorylation. J Neurochem. 2024:168(9):2775–2790. [DOI] [PubMed] [Google Scholar]
  • 18. Xu X, Li C, Zou J, Liu L. MiR-34a targets SIRT1 to reduce p53 deacetylation and promote sevoflurane inhalation anesthesia-induced neuronal autophagy and apoptosis in neonatal mice. Exp Neurol. 2023:368:368114482. [DOI] [PubMed] [Google Scholar]
  • 19. Zhang H, Yan L. Solasonine relieves sevoflurane-induced neurotoxicity via activating the AMP-activated protein kinase/FoxO3a pathway. Hum Exp Toxicol. 2022:41:9603271211069984. [DOI] [PubMed] [Google Scholar]
  • 20. Qin JH, Zhang XR, He L, Zhu J, Ma QJ. Effect of sevoflurane and halothane anesthesia on cognitive function and immune function in young rats. Saudi. J Biol Sci. 2018:25(1):47–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, Akbalik G, Wang M, Glock C, Quedenau C, et al. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci. 2015:18(4):603–610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Wu R, Yun Q, Zhang J, Wang Z, Zhang X, Bao J. Knockdown of circular RNA tousled-like kinase 1 relieves ischemic stroke in middle cerebral artery occlusion mice and oxygen-glucose deprivation and reoxygenation-induced N2a cell damage. Bioengineered. 2022:13(2):3434–3449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Qiu B, Qi X, Wang J. CircTLK1 downregulation attenuates high glucose-induced human mesangial cell injury by blocking the AKT/NF-kappaB pathway through sponging miR-126-5p/miR-204-5p. Biochem Genet. 2022:60(5):1471–1487. [DOI] [PubMed] [Google Scholar]
  • 24. Chen W, Hou C, Wang Y, Hong L, Wang F, Zhang J. Circular RNA circTLK1 regulates dopaminergic neuron injury during Parkinson's disease by targeting miR-26a-5p/DAPK1. Neurosci Lett. 2022:782:136638. [DOI] [PubMed] [Google Scholar]
  • 25. Zhao X, Zhang X, Zhang X, Jiang T, Zhai J, Wang H, Huang M, Lang R, He Q. MiR-374b-5p inhibits KDM5B-induced epithelial-mesenchymal transition in pancreatic cancer. Am J Cancer Res. 2021:11(8):3907–3920. [PMC free article] [PubMed] [Google Scholar]
  • 26. Li H, Liang J, Qin F, Zhai Y. MiR-374b-5p-FOXP1 feedback loop regulates cell migration, epithelial-mesenchymal transition and chemosensitivity in ovarian cancer. Biochem Biophys Res Commun. 2018:505(2):554–560. [DOI] [PubMed] [Google Scholar]
  • 27. He S, Huang L, Shao C, Nie T, Xia L, Cui B, Lu F, Zhu L, Chen B, Yang Q. Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson's disease. Transl Neurodegener. 2021:10(1):25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Guan X, Peng Q, Wang J. Sevoflurane activates MEF2D-mediated Wnt/beta-catenin signaling pathway via microRNA-374b-5p to affect renal ischemia/reperfusion injury. Immunopharmacol Immunotoxicol. 2022:44(4):603–612. [DOI] [PubMed] [Google Scholar]
  • 29. Yu J, Li C. Role of lncRNA MAGI2-AS3 in lipopolysaccharide-induced nucleus pulposus cells injury by regulating miR-374b-5p/interleukin-10 axis. Immun Inflamm Dis. 2023:11(4):e772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Liang TY, Peng SY, Ma M, Li HY, Wang Z, Chen G. Protective effects of sevoflurane in cerebral ischemia reperfusion injury: a narrative review. Med Gas Res. 2021:11(4):152–154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Nasiri-Valikboni A, Rashid M, Azimi A, Zarei H, Yousefifard M. Protective effect of sevoflurane on myocardial ischemia-reperfusion injury: a systematic review and meta-analysis. Int J Surg. 2024:110(11):7311–7330. [DOI] [PMC free article] [PubMed] [Google Scholar]

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