|Year : 2021 | Volume
| Issue : 4 | Page : 152-154
Protective effects of sevoflurane in cerebral ischemia reperfusion injury: a narrative review
Tian-Yu Liang1, Song-Yang Peng1, Mian Ma2, Hai-Ying Li1, Zhong Wang1, Gang Chen1
1 Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
2 Department of Neurosurgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu Province, China
|Date of Submission||09-Apr-2020|
|Date of Decision||21-Apr-2020|
|Date of Acceptance||27-Apr-2020|
|Date of Web Publication||28-Jun-2021|
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province
Department of Neurosurgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu Province
Source of Support: None, Conflict of Interest: None
Ischemia/reperfusion (I/R) injury is a phenomenon that the reperfusion of ischemic organs or tissues aggravates their damage, which poses a serious health threat and economic burden to the world. I/R gives rise to a series of physiological and pathological world, including inflammatory response, oxidative stress, brain edema, blood-brain barrier destruction, and neuronal death. Therefore, finding effective treatment measures is extremely important to the recovery of I/R patients and the improvement of long-term quality of life. Sevoflurane is an important volatile anesthetic which has been reported to reduce myocardial I/R damage and infarct size. Sevoflurane also has anti-inflammatory and neuroprotective effects. As reported sevoflurane treatment could reduce nerve function injury, cerebral infarction volume and the level of inflammatory factors. At the same time, there is evidence that sevoflurane can reduce neuron apoptosis and antioxidant stress. The protective effect of sevoflurane in brain injury has been proved to be existed in several aspects, so that a comprehensive understanding of its neuroprotective effect is helpful to exploit new treatment paths for I/R, provide clinicians with new clinical treatment decisions, contribute to the effective treatment of I/R patients and the improvement of quality of life after I/R healing.
Keywords: central nervous system; cerebral blood flow; cerebral ischemia-reperfusion injury; inflammatory response; inhalant anesthetic; microglia; neuroprotection; sevoflurane
|How to cite this article:|
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;11:152-4
|How to cite this URL:|
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 [serial online] 2021 [cited 2021 Aug 1];11:152-4. Available from: https://www.medgasres.com/text.asp?2021/11/4/152/318860
Tian-Yu Liang, Song-Yang Peng
#Both authors contributed equally to this work.
Funding: This work was supported by Suzhou Youth Science and Technology Project, China (No. KJXW 2017029).
| Introduction|| |
Cerebral ischemia/reperfusion (I/R) injury can cause the most common stroke-related death and disability worldwide and has a poor prognosis., Prompt ischemia-reperfusion can prevent severe neurological defects and death. However, it may further exacerbate neuron death and neurological dysfunction. Due to blocked cerebral arteries and inadequate blood supply, I/R in the brain leads to complex pathophysiological processes leading to further I/R injury. In addition, autophagy and inflammation emerge after I/R contribute to further damages to the neuron death and cell death. In the process of cerebral I/R, there are a large number of inflammatory factors in the ischemic focus., While restoring blood flow to ischemic organs is critical to preventing irreversible tissue damage, reperfusion itself may lead to local and systemic inflammatory responses that may increase tissue damage beyond that caused by ischemia alone. I/R injury is characterized by oxidation products, complement activation, leukocyte-endothelial cell adhesion, platelets-leukocyte aggregation, increased microtubule permeability, and decreased endothelium-dependent diastolic function. The most severe I/R damage can lead to multiple organ dysfunction or death.
Sevoflurane is an inhaled anesthetic widely used in surgery. Sevoflurane has the activity of anti-oxidative stress and anti-inflammation, and can protect organs from the damage caused by stress. It is now recognized that sevoflurane is a safe inhaled anesthetic and has the advantages of inducing rapid and rapid resuscitation as an anesthetic inducer. Existing studies have indicated that sevoflurane preconditioning for neurological protection is a double-edged sword for patients with neurological defects. For one thing, sevoflurane can relieve the inflammatory response, reducing cell death, the activation of innate immune cells. For another thing, sevoflurane can inhibit the release of related cytokines, increase cognitive dysfunction and amplify brain damage. However, the mechanism of sevoflurane’s function after I/R has not been fully studied. This paper presents a comprehensive description of several existing mechanisms, which is conducive to the full understanding of sevoflurane. More importantly, it is helpful for clinicians to grasp the use of sevoflurane and promote the safe and effective use of sevoflurane in clinical practice.
| Mechanisms of Sevoflurane|| |
Existing studies have shown that sevoflurane is a vasodilator, and in vitro and in vivo experiments have shown that sevoflurane can effectively protect neurons following cerebral ischemia through several pathways. Although its protective effect has been an issue of concern, the mechanism of sevoflurane remains to be further studied. Signal transduction pathway is the main way for cells to transmit information. At present, several signal transduction pathways for sevoflurane to play a neuroprotective role have been discovered, such as Janus kinase-signal transducer and activator of transcription pathway, Toll like receptor 4/nuclear factor-κB pathway, TWIK-related K+ channel 1 channel, phosphoinositide 3-kinase/Akt signaling pathway, Akt signaling pathway, protein kinase B/nuclear factor-erythroid 2-related factor 2 pathway. Through these signaling pathways, sevoflurane reduces inflammation, activates glial cells, inhibits neuronal apoptosis, and protects damaged brain tissue.
Sevoflurane attenuates the inflammatory response
It is widely known that sevoflurane has the benefits of anti-inflammatory and neuroprotection. In 2004, Nader et al. pointed out that volatile anesthetics, such as sevoflurane, could attenuate the inflammatory response, in their report, the inhalation of sevoflurane could reduce the expression of inflammatory factors of tumor necrosis factor-α and interleukin-1β in plasma. In vivo studies have also shown that sevoflurane post-treatment can reduce the inflammatory response in the cerebral infarction area and reduce the concentration of serum pro-inflammatory cytokines in rats after cerebral I/R injury. It has been reported that sevoflurane treatment can enhance the barrier function of the brain, protect the vascular endothelial integrity, and maintain the cell junction protein arrangement, which effectively increases cerebral blood flow, and also enhances the anti-inflammatory ability of the body. Numerous subsequent studies have shown that sevoflurane has an anti-inflammatory effect to protect damaged brain tissue after I/R by reducing the production of inflammatory factors through various pathways. This is the key step in the recovery of patients with cerebral I/R injury.,
Sevoflurane helps macrophages/microglia perform immune function
Microglia and macrophages are the most effective central nervous system damage repair and regeneration regulators and undertake an important character in innate immunity and acquired immunity. After I/R, the activated microglia not only release neurotrophic factors, but also secrete a variety of pro-inflammatory cytokines, nitric oxide and other factors that can aggravate the injury. In case of I/R, infiltration and migration of microglia to the spinal cord is associated with damage to the vasculature, caused by substances released by activated microglia, matrix metalloproteinases. The researchers found that sevoflurane pretreatment prevented an increase in the number of harmful microglia in the spinal cord of rats with I/R damage. Current studies also suggest that sevoflurane preconditioning may affect motor function by inhibiting microglial cell infiltration and migration of injured neurons, and sevoflurane preconditioning inhibits the production of pro-inflammatory chemokines and cytokines and neuronal cell apoptosis after spinal cord I/R. However, there is increasing evidence that microglia/macrophages have dual functions, one is to amplify ischemic damage by releasing proinflammatory neurotoxins, and the other is to support brain recovery after stroke by removing cell debris and secreting nutrient factors., It was found that after sevoflurane administration, reactive microglia/macrophages began to accumulate in and around the lesion site on the 3rd day after stroke, showing a highly branched form and rapid response., The phagocytosing microglia/macrophages with amoeboid morphology have been confirmed to promote neural survival by clearing potential toxic debris and reducing subsequent secondary brain damage. After sevoflurane pretreatment, its derivative microglia/macrophages rapidly transformed into amoebia-like morphology on the third day after I/R injury and accumulated in the infarcted cortex and striatum, indicating that sevoflurane improves the phagocytic efficiency by increasing the phagocytic capacity of each cell. Compared with the control group, the number of phagocytes in the infarction area of sevoflurane pretreatment group increased significantly on the 5th day after injury, indicating that sevoflurane pretreatment could collect more phagocytes and enhance their phagocytic ability.
Other mechanisms that sevoflurane protects central nervous system
Sevoflurane has attracted more and more attention in clinical application as an inhaled anesthetic in recent years. Existing studies have revealed that sevoflurane can reduce the release of excitatory neurotransmitters such as catechol and glutamine caused by cerebral ischemia injury and relieved the re-stimulation to neurons. After cerebral I/R, the production of reactive oxygen species increases dramatically, which is exceeding the endogenous antioxidant system and leading to oxidative stress. The brain is particularly vulnerable to oxidative stress because it consumes a lot of oxygen, rich in polyunsaturated fatty acids and low levels of endogenous antioxidants. Sevoflurane can reduce the release of free radicals, showing antioxidant properties. Sevoflurane can also inhibit the voltage-gated calcium channel and protein kinase C in the presynaptic membrane of neurons, up-regulate the hippocampal anti-apoptotic proteins Bcl-2 and murine double minute-2, and inhibit the expression of ischemia-mediated apoptotic activating protein Bax, thus protecting the central nervous system [Table 1].
|Table 1: Neuroprotective effects of sevoflurane and the related mechanisms|
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| Future and Prospect|| |
Although the molecular mechanism of sevoflurane to protect injured brain tissue has not been fully elucidated, its application value has been paid more and more attention, including improving cerebral blood flow, inhibiting inflammatory response, reducing infarct area, etc. It is expected that sevoflurane will be widely used in the treatment and recovery of clinical patients.
Manuscript drafting: TYL and SYP; manuscript writing: HYL and MM; manuscript revision: ZW and GC. All the authors read and approved the final version of the manuscript for publication.
Conflicts of interest
The authors have no conflicts of interests to declare.
This work was supported by Suzhou Youth Science and Technology Project, China (No. KJXW 2017029).
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| References|| |
Yang Z, Weian C, Susu H, Hanmin W. Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms. Eur J Pharmacol
Stegner D, Klaus V, Nieswandt B. Platelets as modulators of cerebral ischemia/reperfusion injury. Front Immunol
Wang J, Xu Z, Chen X, et al. MicroRNA-182-5p attenuates cerebral ischemia-reperfusion injury by targeting Toll-like receptor 4. Biochem Biophys Res Commun
Huang J, Upadhyay UM, Tamargo RJ. Inflammation in stroke and focal cerebral ischemia. Surg Neurol
Wu H, Tang C, Tai LW, et al. Flurbiprofen axetil attenuates cerebral ischemia/reperfusion injury by reducing inflammation in a rat model of transient global cerebral ischemia/reperfusion. Biosci Rep
Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev
Szabó C. The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock
Shan J, Sun L, Wang D, Li X. Comparison of the neuroprotective effects and recovery profiles of isoflurane, sevoflurane and desflurane as neurosurgical pre-conditioning on ischemia/reperfusion cerebral injury. Int J Clin Exp Pathol
Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull
Wang Y, Zhang X, Tian J, Liu G, Li X, Shen D. Sevoflurane alleviates LPS induced acute lung injury via the microRNA 27a 3p/TLR4/MyD88/NF κB signaling pathway. Int J Mol Med
Herrmann IK, Castellon M, Schwartz DE, et al. Volatile anesthetics improve survival after cecal ligation and puncture. Anesthesiology
Zhu YM, Gao X, Ni Y, et al. Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar formation after ischemia-reperfusion brain injury. Neuroscience
Hwang JW, Jeon YT, Lim YJ, Park HP. Sevoflurane postconditioning-induced anti-inflammation via inhibition of the Toll-like receptor-4/nuclear factor kappa b pathway contributes to neuroprotection against transient global cerebral ischemia in rats. Int J Mol Sci
Wang JY, Feng Y, Fu YH, Liu GL. Effect of sevoflurane anesthesia on brain is mediated by lncRNA HOTAIR. J Mol Neurosci
Kim HC, Kim E, Bae JI, et al. Sevoflurane postconditioning reduces apoptosis by activating the JAK-STAT pathway after transient global cerebral ischemia in rats. J Neurosurg Anesthesiol
Shi CX, Ding YB, Jin FYJ, et al. Effects of sevoflurane post-conditioning in cerebral ischemia-reperfusion injury via TLR4/NF-κB pathway in rats. Eur Rev Med Pharmacol Sci
Pan L, Yang F, Lu C, Jia C, Wang Q, Zeng K. Effects of sevoflurane on rats with ischemic brain injury and the role of the TREK-1 channel. Exp Ther Med
Zhang Y, Tian SY, Li YW, et al. Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage in a rat model via PI3K/Akt signaling pathway. Gene
Wen XR, Fu YY, Liu HZ, et al. Neuroprotection of sevoflurane against ischemia/reperfusion-induced brain injury through inhibiting JNK3/Caspase-3 by enhancing Akt signaling pathway. Mol Neurobiol
Li B, Sun J, Lv G, et al. Sevoflurane postconditioning attenuates cerebral ischemia-reperfusion injury via protein kinase B/nuclear factor-erythroid 2-related factor 2 pathway activation. Int J Dev Neurosci
Nader ND, Li CM, Khadra WZ, Reedy R, Panos AL. Anesthetic myocardial protection with sevoflurane. J Cardiothorac Vasc Anesth
Restin T, Kajdi ME, Schlapfer M, et al. Sevoflurane protects rat brain endothelial barrier structure and function after hypoxia-reoxygenation injury. PLoS One
Carrillo-Jimenez A, Deniz Ö, Niklison-Chirou MV, et al. TET2 regulates the neuroinflammatory response in microglia. Cell Rep
Patel AR, Ritzel R, McCullough LD, Liu F. Microglia and ischemic stroke: a double-edged sword. Int J Physiol Pathophysiol Pharmacol
Li XQ, Cao XZ, Wang J, Fang B, Tan WF, Ma H. Sevoflurane preconditioning ameliorates neuronal deficits by inhibiting microglial MMP-9 expression after spinal cord ischemia/reperfusion in rats. Mol Brain
Morgan SC, Taylor DL, Pocock JM. Microglia release activators of neuronal proliferation mediated by activation of mitogen-activated protein kinase, phosphatidylinositol-3-kinase/Akt and delta-Notch signalling cascades. J Neurochem
Ma Y, Wang J, Wang Y, Yang GY. The biphasic function of microglia in ischemic stroke. Prog Neurobiol
Davalos D, Grutzendler J, Yang G, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci
Perego C, Fumagalli S, De Simoni MG. Temporal pattern of expression and colocalization of microglia/macrophage phenotype markers following brain ischemic injury in mice. J Neuroinflammation
Dang DD, Saiyin H, Yu Q, Liang WM. Effects of sevoflurane preconditioning on microglia/macrophage dynamics and phagocytosis profile against cerebral ischemia in rats. CNS Neurosci Ther
Zhang D, Chiu KM, Wang W, Sun D. Effects of conditioning with sevoflurane before reperfusion on hippocampal ischemic injury and insulin-like growth factor-1 expression in rats. Chin J Physiol
Toner CC, Connelly K, Whelpton R, et al. Effects of sevoflurane on dopamine, glutamate and aspartate release in an in vitro model of cerebral ischaemia. Br J Anaesth
Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol
Canas PT, Velly LJ, Labrande CN, et al. Sevoflurane protects rat mixed cerebrocortical neuronal-glial cell cultures against transient oxygen-glucose deprivation: involvement of glutamate uptake and reactive oxygen species. Anesthesiology
Pape M, Engelhard K, Eberspächer E, et al. The long-term effect of sevoflurane on neuronal cell damage and expression of apoptotic factors after cerebral ischemia and reperfusion in rats. Anesth Analg
. 2006;103:173-179, table of contents.