2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      NLRP3 Inflammasome: A Potential Target in Isoflurane Pretreatment Alleviates Stroke-Induced Retinal Injury in Diabetes

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Ischemic stroke remains a devastating disease which is the leading cause of death worldwide. Visual impairment after stroke is a common complication which may lead to vision loss, greatly impacting life quality of patients. While ischemic stroke is traditionally characterized by a blockage of blood flow to the brain, this may coincide with reduced blood flow to the eye, resulting in retinal ischemia and leading to visual impairment. Diabetes increases the risk of ischemic stroke and induces diabetic retinopathy; the latter may be more sensitive to the ischemic retinal injury. In diabetic status, the underlying mechanism in stroke-induced retinal injury has not been fully clarified. The NLR pyrin domain containing 3 (NLRP3) inflammasome is an important activator of inflammation, which may play a critical role in catalyzing and forming certain pro-inflammatory cytokines in both cerebral and retinal ischemia. Isoflurane has been demonstrated to inhibit the activation of the NLRP3 inflammasome and show neuroprotective effects. In this study, we established a diabetic mouse model and performed the middle cerebral artery occlusion procedure to induce ischemic stroke. Our results revealed that cerebral ischemia-induced retinal injury in the diabetic model. Isoflurane pretreatment alleviated the cerebral and retinal injury after ischemic stroke. Of note, isoflurane pretreatment inhibited the NLRP3 inflammasome activation in the retina, indicating that isoflurane pretreatment may provide substantial retinal protection in stroke-induced retinal injury in diabetes.

          Related collections

          Most cited references47

          • Record: found
          • Abstract: found
          • Article: not found

          A role for mitochondria in NLRP3 inflammasome activation.

          An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Prevalence, Incidence, and Mortality of Stroke in China: Results from a Nationwide Population-Based Survey of 480 687 Adults.

            China bears the biggest stroke burden in the world. However, little is known about the current prevalence, incidence, and mortality of stroke at the national level, and the trend in the past 30 years.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Diabetic retinopathy.

              Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth-factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising. Copyright 2010 Elsevier Ltd. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                08 July 2021
                2021
                : 15
                : 697449
                Affiliations
                [1] 1Department of Anesthesiology, Zhujiang Hospital of Southern Medical University , Guangzhou, China
                [2] 2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University , Guangzhou, China
                [3] 3Department of Physiology, Temerty Faculty of Medicine, University of Toronto , Toronto, ON, Canada
                [4] 4Department of Anesthesiology, Liuzhou People’s Hospital, The Affiliated Liuzhou People’s Hospital of Guangxi Medical University , Liuzhou, China
                [5] 5Department of Surgery, Temerty Faculty of Medicine, University of Toronto , Toronto, ON, Canada
                [6] 6Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto , Toronto, ON, Canada
                [7] 7Leslie Dan Faculty of Pharmacy, University of Toronto , Toronto, ON, Canada
                Author notes

                Edited by: Junlei Chang, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS), China

                Reviewed by: Tao Tao, Southern Medical University, China; Bin Cai, Fujian Medical University, China

                *Correspondence: Feng-Xian Li lifengxian81@ 123456smu.edu.cn Hong-Fei Zhang zhanghongfei@ 123456smu.edu.cn

                These authors have contributed equally to this work and share first authorship

                Specialty section: This article was submitted to Cellular Neurophysiology, a section of the journal Frontiers in Cellular Neuroscience

                Article
                10.3389/fncel.2021.697449
                8295463
                34305534
                661566f1-a5cc-40fe-b641-a529821965b2
                Copyright © 2021 Lin, Lin, Zhang, Guo, Ovcjak, You, Feng, Sun, Li and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 April 2021
                : 16 June 2021
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 47, Pages: 9, Words: 6053
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Funded by: Natural Science Foundation of Guangdong Province 10.13039/501100003453
                Categories
                Cellular Neuroscience
                Original Research

                Neurosciences
                ischemic stroke (is),retinal injury,diabetes,nlrp3 inflammasome,isoflurane
                Neurosciences
                ischemic stroke (is), retinal injury, diabetes, nlrp3 inflammasome, isoflurane

                Comments

                Comment on this article