Isoflurane Impairs Motor Function Recovery by Increasing Neuroapoptosis and Degeneration During Spinal Ischemia–Reperfusion Injury in Rats

Fang, Shih Yuan; Lee, Jung Shun; Roan, Jun‐Neng; Tsai, Yu Chuan; Lam, Chen Fuh

doi:10.1213/ane.0000000000001704

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…Isoflurane is a traditional anesthetic. Previous study has revealed that the application of isoflurane aggravates apoptosis and leads to damage in the central nervous system during cerebral ischemia‐reperfusion injury process in rats (Fang et al., 2017). Moreover, isoflurane is also known to induce damage in neuronal cells by activating the expression of p‐NF‐κB (Schallner et al., 2014).…”

Section: Discussionmentioning

confidence: 99%

Atractylenolide III alleviates isoflurane‐induced injury in rat hippocampal neurons by activating the PI3K/Akt/mTOR pathway

Zhu

Wang

et al. 2021

J Food Biochem

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The use of anesthetics relieves discomfort in patients during operation, but extensive application of anesthetics can cause damage to the nervous system. Atractylenolide III (ATL‐III) is an active ingredient derived from Baizhu, which is a kind of traditional Chinese medicines. Recent studies have shown that ATL‐III alleviates inflammation and oxidative stress in various tissues by regulating the PI3K/Akt/mTOR signaling pathway. However, whether or not the application of ATL‐III could relieve isoflurane‐induced damage in rat hippocampal neurons remains unclear. In this study, rats were stimulated with isoflurane and treated with ATL‐III (intragastric administration) simultaneously. After rats were sacrificed, apoptosis and autophagy in the hippocampal neurons were assessed using TUNEL assays and western blotting, respectively. Then, the expression of inflammatory factors was determined by q‐PCR and ELISA. The levels of p‐PI3K, p‐Akt, and p‐mTOR were quantified by western blotting. We found that ATL‐III relieved isoflurane‐induced apoptosis, autophagy and inflammation in hippocampal neurons in rats. ATL‐III treatment also inhibited the expression of TNF‐α, IL‐1β, and IL‐6 in these cells. Furthermore, ATL‐III promoted the expression of p‐PI3K, p‐Akt, and p‐mTOR in the hippocampal neurons. All these results indicated that ATL‐III alleviated isoflurane‐induced injury in rat hippocampal neurons by activating the PI3K/Akt/mTOR signaling pathway. Practical applications Whether or not Atractylenolide III (ATL‐III) could alleviate neurotoxicity induced by anesthetics is unclear. In this study, we investigated the effect of ATL‐III on anesthetic‐induced nervous system damage. The findings from this study could also provide a novel therapy for the treatment of patients with anesthetic‐induced nerve injury.

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Section: Discussionmentioning

confidence: 99%

Atractylenolide III alleviates isoflurane‐induced injury in rat hippocampal neurons by activating the PI3K/Akt/mTOR pathway

Zhu

Wang

et al. 2021

J Food Biochem

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“…The SCI mouse model was established as previously described (Le Corre et al, ). Isoflurane (1.5% v/v in oxygen) was delivered to the animals via a costume‐built oronasal mask (Fang et al, ). Laminectomy at the T11–13 level was conducted to expose the spinal cord.…”

Section: Methodsmentioning

confidence: 99%

Triptolide improves spinal cord injury by promoting autophagy and inhibiting apoptosis

Zhu

Ruan

Yang

et al. 2019

Cell Biology International

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We investigated the effect of triptolide (TP) on spinal cord injury (SCI), and its underlying mechanism. Following the establishment of the SCI model using YFP H‐line transgenic mice, TP was intraperitoneally injected at a dose of 0.2 mg/kg once daily for 7 days. Behavioral tests, Nissl staining, and hematoxylin–eosin staining were employed to assess motor function recovery and neuronal cell death. Western blot and immunofluorescence staining were used to assess autophagy‐associated proteins (LC3B, p62, Beclin‐1) and the apoptosis‐associated proteins (Bcl‐2, caspase‐3, Bax). The TP‐treated group showed improved motor functions, and reduced neuronal cell death. Also, significant upregulation of Bcl‐2 and LC3B expressions, with the downregulation of p62, Bax and caspase‐3 expressions were found in the TP‐treated group. Additionally, phosphorylation of extracellular signal‐regulated protein kinases 1 and 2 (ERK1 and ERK2) was decreased in the TP‐treated group. TP mediates its protective effect in SCI by promoting the autophagic pathway while inhibiting the MAPK/ERK1/2 signaling pathway. These results demonstrate the therapeutic potential of TP in SCI.

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“…In neuronal injury or neurodegenerative disease, both neuroprotective and neurotoxic effects of isoflurane are discussed [45,49]. Recently, Fang et al described an in vivo rat model of lumbar spinal cord ischemia (SCI) by cross-clamping of the thoracic aorta at the level of T5 [72]. Ischemia was performed for 25 min, followed by cord reperfusion for up to 48 h. Isoflurane 1.5 vol% was applied via inhalation perioperatively.…”

Section: The Role Of Anesthetic Agents On Ho-1 Modulationmentioning

confidence: 99%

“…SCI-induced HO-1 protein expression was further induced by isoflurane. This increase was interpreted as an enhanced inflammatory response [72].…”

Section: The Role Of Anesthetic Agents On Ho-1 Modulationmentioning

confidence: 99%

The Role of Heme Oxygenase-1 in Remote Ischemic and Anesthetic Organ Conditioning

Bauer

Raupach

2019

Antioxidants

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The cytoprotective effects of the heme oxygenase (HO) pathway are widely acknowledged. These effects are mainly mediated by degradation of free, pro-oxidant heme and the generation of carbon monoxide (CO) and biliverdin. The underlying mechanisms of protection include anti-oxidant, anti-apoptotic, anti-inflammatory and vasodilatory properties. Upregulation of the inducible isoform HO-1 under stress conditions plays a crucial role in preventing or reducing cell damage. Therefore, modulation of the HO-1 system might provide an efficient strategy for organ protection. Pharmacological agents investigated in the context of organ conditioning include clinically used anesthetics and sedatives. A review from Hoetzel and Schmidt from 2010 nicely summarized the effects of anesthetics on HO-1 expression and their role in disease models. They concluded that HO-1 upregulation by anesthetics might prevent or at least reduce organ injury due to harmful stimuli. Due to its clinical safety, anesthetic conditioning might represent an attractive pharmacological tool for HO-1 modulation in patients. Remote ischemic conditioning (RIC), first described in 1993, represents a similar secure option to induce organ protection, especially in its non-invasive form. The efficacy of RIC has been intensively studied herein, including on patients. Studies on the role of RIC in influencing HO-1 expression to induce organ protection are emerging. In the first part of this review, recently published pre-clinical and clinical studies investigating the effects of anesthetics on HO-1 expression patterns, the underlying signaling pathways mediating modulation and its causative role in organ protection are summarized. The second part of this review sums up the effects of RIC.

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Isoflurane Impairs Motor Function Recovery by Increasing Neuroapoptosis and Degeneration During Spinal Ischemia–Reperfusion Injury in Rats

Cited by 6 publications

References 33 publications

Atractylenolide III alleviates isoflurane‐induced injury in rat hippocampal neurons by activating the PI3K/Akt/mTOR pathway

Atractylenolide III alleviates isoflurane‐induced injury in rat hippocampal neurons by activating the PI3K/Akt/mTOR pathway

Triptolide improves spinal cord injury by promoting autophagy and inhibiting apoptosis

The Role of Heme Oxygenase-1 in Remote Ischemic and Anesthetic Organ Conditioning

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