Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on cognitive impairment

Zuo, Chunlong; Wang, Chun-Man; Liu, Jin; Shen, Ting; Zhou, Jiang-Ping; Hao, Xinrui; Pan, Yizhao; Liu, Hua-Cheng; Lian, Qingquan; Lin, Han Chieh

doi:10.1111/cns.12794

Cited by 30 publications

(23 citation statements)

References 62 publications

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“…First, the current study is comparing tibial fracture vs sham‐operated animals which were anesthetized with isoflurane. Prior studies have described altered responses to aging with isoflurane alone in nonsurgical animals . Thus, it is possible that enhanced neuroinflammation in the aged brain after tibial fracture surgery may be due to some interaction between surgery and anesthesia, or other perioperative variables.…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies have described altered responses to aging with isoflurane alone in nonsurgical animals. 35,36 Thus, it is possible that enhanced neuroinflammation in the aged brain after tibial fracture surgery may be due to some interaction between surgery and anesthesia, or other perioperative variables. However, it should be noted that isoflurane exposure time was relatively short in our tibial fracture surgery model (about 15-20 minutes) compared to those reports investigating isoflurane alone.…”

Section: Discussionmentioning

confidence: 99%

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Aging alters Hv1‐mediated microglial polarization and enhances neuroinflammation after peripheral surgery

et al. 2019

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Perioperative neurocognitive disorders have been widely recognized as common adverse events after surgical intervention. Aging is one of the most important independent risk factors for worsened cognitive outcome, and this deterioration is linked to exacerbated microglia‐mediated neuroinflammation in the aged brain. Under pathological stimulation, microglia are capable of polarizing toward proinflammatory M1 and anti‐inflammatory M2 phenotypes. In the present study, we examined how aging affects microglial responses and neuroinflammation following peripheral surgery. Adult (2‐3 months) and aged (18 months old) male C57/BL6 mice were subjected to tibial fracture or sham surgery. Aged mice exhibited higher level of tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in the hippocampus. The expression of synaptic protein synaptophysin (SYP) was also markedly reduced in the aged brain after the surgery. Both adult and aged mice showed significant increases in M1 microglial polarization (CD16/32). In contrast, tibial fracture surgery induced a decreased M2 microglial polarization (CD206, Ym1/2, Arg1) in aged brain but enhanced M2 microglial polarization in adult brain. Aged mice have upregulated voltage‐gated proton channel (Hv1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression compared with adult mice. The percentage of CD16/32‐positive M1 microglia colabeling with Hv1 was higher in aged mice after tibial fracture surgery. Thus, Hv1/NADPH oxidase upregulation in the aged brain may shift the dynamic equilibrium of microglial activation toward M1 polarization and exaggerate postoperative neuroinflammatory responses after peripheral surgical intervention.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Aging alters Hv1‐mediated microglial polarization and enhances neuroinflammation after peripheral surgery

et al. 2019

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“…2019;34(12):e201901205 a great inspiration. Many labs use isoflurane in aged rats and mice to examine cognitive function 19,20 . In our study, the effects of HupA on cognitive function in aged rats after anesthesia with isoflurane were investigated.…”

Section: ■ Discussionmentioning

confidence: 99%

Effects of huperzine A on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia

2019

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Purpose: To investigate the effects of huperzine A (HupA) on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia.Methods: Thirty-six Sprague Dawley rats (20-22 months old) were randomly divided into control, isofluran, and isoflurane+HupA groups; 12 rats in each group. The isoflurane+HupA group was intraperitoneally injected with 0.2 mg/kg of HupA. After 30 min, isoflurane inhalation anesthesia was performed in the isoflurane and isoflurane+HupA groups. After 24 h from anesthesia, Morris water maze experiment and open-field test were performed. Hippocampal inflammatory and neurotrophic factors were determined.Results: Compared with isoflurane group, in isofluran+HupA group the escape latency of rats was significantly decreased (P < 0.05), the original platform quadrant residence time and traversing times were significantly increased (P < 0.05), the central area residence time was significantly increased (P < 0.05), the hippocampal tumor necrosis factor α, interleukin 6 and interleukin 1β levels were significantly decreased (P < 0.05), and the hippocampal nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 levels were significantly increased (P < 0.05). Conclusion:HupA may alleviate the cognitive impairment in rats after isoflurane anesthesia by decreasing inflammatory factors and increasing hippocampal neurotrophic factors in hippocampus tissue.Effects of huperzine A on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia Cai Y et al. Acta Cir Bras. 2019;34(12):e201901205 Determination of hippocampal inflammatory and neurotrophic factorsAfter the behavioral test, the rats were executed by cervical dislocation. The head was cut off and the Effects of huperzine A on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia Cai Y et al. Cir Bras. 2019;34(12):e201901205 ActaEffects of huperzine A on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia Cai Y et al.

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“…Isoflurane is an isomeride of enflurane, which was commonly used in inhalation anesthesia. But, isoflurane can induce neurogenetic damage and neurocognitive disorder, even accelerate the process of Alzheimer's disease [17][18][19].With a view to the adverse effects of inhalational anesthetic compare to intravenous anesthetic. EIso was manufactured by West China Hospital of Sichuan University, which liquid isoflurane was mixed with intralipid at the final concentration of 8% (v/v).…”

Section: Discussionmentioning

confidence: 99%

Emulsified isoflurane alleviates rat islet beta cell RIN-m5F apoptosis induced by glucose via inhibiting endoplasmic reticulum stress

Dong

Yang

Zhao

et al. 2019

Preprint

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Background Diabetes mellitus (DM) is a critical disease that considered a detriment to the health of people all over the world. Endoplasmic reticulum stress (ERS) is the response cause by endoplasmic reticulum misfolded and unfolded protein aggregation, which induces cell apoptosis. Our previous work showed that EIso could alleviate ERS in lung reperfusion injury. This study aimed to elucidate whether Emulsified isoflurane (EIso) could alleviate apoptosis induced by glucose in rat islet beta cell RIN-m5F via inhibiting ERS. Methods RIN-m5F cells were divided into five groups: Control group, cultured in 0.1M glucose for 24h (0.1G group), culture in 0.3M glucose for 24h (0.3G group), culture in 0.3M glucose with 57uM EIso for 24h (0.3G+57E group), and culture in 0.3M glucose with 76uM EIso for 24h (0.3G+76E group). First, the cellular proliferation was measured by MTT assay, and the level of insulin secretion was measured with ELISA kit. Second, the expression of Bax and Bcl-2 were detected by Western blotting. The level of caspase-3 activity was assessed by colorimetric method. Finally, the CHOP and GRP78 expression were detected by Western blotting. The level of ATF6, Xbp1 and eIF2α mRNA were assessed by qRT-PCR after treated with EIso for 24h. Results High glucose induced significant loss of RIN-m5F cell viability, and stimulated the secretion of insulin; EIso improved the survival and protected the function of RIN-m5F. Compare to 0.3G group, treatment with EIso inhibited the activity of caspase-3, decreased the expression of Bax and increased the expression of Bcl-2. The expression of CHOP and GRP78 were inhibited by EIso at 24 h after treatment, and decrement of CHOP and GRP78 expression were correlated with EIso concentration. The level of ATF6, Xbp1 and eIF2α mRNA of RIN-m5F were enhanced culture with high glucose, but only eIF2α mRNA was decreased by EIso treatment. Conclusion High glucose induces rat islet beta cell RIN-m5F apoptosis and aggravates the function of beta cells. EIso protects beta cells from glucose-induced apoptosis, and anti-apoptosis is mediated, at least in part, by inhibiting ERS.

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Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on cognitive impairment

Abstract: We found an association between isoflurane exposure, impairment of spatial memory, decreasing level of NR2B, and increasing levels of A-beta and P-tau, presumably via the activation of the A1A receptor.

Cited by 30 publications

References 62 publications

Aging alters Hv1‐mediated microglial polarization and enhances neuroinflammation after peripheral surgery

Aging alters Hv1‐mediated microglial polarization and enhances neuroinflammation after peripheral surgery

Effects of huperzine A on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia

Emulsified isoflurane alleviates rat islet beta cell RIN-m5F apoptosis induced by glucose via inhibiting endoplasmic reticulum stress

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