Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2024 Volume 30 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2024 Volume 30 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke

  • Authors:
    • Ensi Luo
    • Zhuo Li
    • Shiying Zhang
    • Yin Wen
    • Zixi Yang
    • Hongke Zeng
    • Hongguang Ding
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Binhaiwan Central Hospital of Dongguan, Dongguan Hospital Affiliated to Medical College of Jinan University, Dongguan, Guangdong 523903, P.R. China, Department of Critical Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China, College of Continuing Education, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China, Department of Emergency Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China
    Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 146
    |
    Published online on: June 21, 2024
       https://doi.org/10.3892/mmr.2024.13270
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Elevated levels of blood glucose in patients with ischemic stroke are associated with a worse prognosis. The present study aimed to explore whether hyperglycemia promotes microglial pyroptosis by increasing the oxygen extraction rate in an acute ischemic stroke model. C57BL/6 mice that underwent middle cerebral artery occlusion were used for assessment of blood glucose level and neurological function. The cerebral oxygen extraction ratio (CERO2), oxygen consumption rate (OCR) and partial pressure of brain tissue oxygen (PbtO2) were measured. To investigate the significance of the NOD‑like receptor protein 3 (NLRP3) inflammasome, NLRP3‑/‑ mice were used, and the expression levels of NLRP3, caspase‑1, full‑length gasdermin D (GSDMD‑FL), GSDMD‑N domain (GSDMD‑N), IL‑1β and IL‑18 were evaluated. In addition, Z‑YVAD‑FMK, a caspase‑1 inhibitor, was used to treat microglia to determine whether activation of the NLRP3 inflammasome was required for the enhancing effect of hyperglycemia on pyroptosis. It was revealed that hyperglycemia accelerated cerebral injury in the acute ischemic stroke model, as evidenced by decreased latency to fall and the percentage of foot fault. Hyperglycemia aggravated hypoxia by increasing the oxygen extraction rate, as evidenced by increased CERO2 and OCR, and decreased PbtO2 in response to high glucose treatment. Furthermore, hyperglycemia‑induced microglial pyroptosis was confirmed by detection of increased levels of caspase‑1, GSDMD‑N, IL‑1β and IL‑18 and a decreased level of GSDMD‑FL. However, the knockout of NLRP3 attenuated these effects. Pharmacological inhibition of caspase‑1 also reduced the expression levels of GSDMD‑N, IL‑1β and IL‑18 in microglial cells. These results suggested that hyperglycemia stimulated NLRP3 inflammasome activation by increasing the oxygen extraction rate, thus leading to the aggravation of pyroptosis following ischemic stroke.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Feske SK: Ischemic stroke. Am J Med. 134:1457–1464. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, et al: Heart disease and stroke statistics-2022 update: A report from the american heart association. Circulation. 145:e153–e639. 2022. View Article : Google Scholar : PubMed/NCBI

3 

Herpich F and Rincon F: Management of acute ischemic stroke. Crit Care Med. 48:1654–1663. 2020. View Article : Google Scholar : PubMed/NCBI

4 

Gray CS, Hildreth AJ, Sandercock PA, O'Connell JE, Johnston DE, Cartlidge NE, Bamford JM, James OF and Alberti KGMM; GIST Trialists Collaboration, : Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: The UK glucose insulin in stroke trial (GIST-UK). Lancet Neurol. 6:397–406. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Johnston KC, Bruno A, Pauls Q, Hall CE, Barrett KM, Barsan W, Fansler A, Van de Bruinhorst K, Janis S and Durkalski-Mauldin VLD; Neurological Emergencies Treatment Trials Network and the SHINE Trial Investigators, : Intensive vs standard treatment of hyperglycemia and functional outcome in patients with acute ischemic stroke: The SHINE randomized clinical trial. JAMA. 322:326–335. 2019. View Article : Google Scholar : PubMed/NCBI

6 

Desilles JP, Syvannarath V, Ollivier V, Journé C, Delbosc S, Ducroux C, Boisseau W, Louedec L, Di Meglio L, Loyau S, et al: Exacerbation of thromboinflammation by hyperglycemia precipitates cerebral infarct growth and hemorrhagic transformation. Stroke. 48:1932–1940. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Ergul A, Li W, Elgebaly MM, Bruno A and Fagan SC: Hyperglycemia, diabetes and stroke: Focus on the cerebrovasculature. Vascul Pharmacol. 51:44–49. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Jia J, Yang L, Chen Y, Zheng L, Chen Y, Xu Y and Zhang M: The role of microglial phagocytosis in ischemic stroke. Front Immunol. 12:7902012022. View Article : Google Scholar : PubMed/NCBI

9 

Ding H, Li Y, Wen M, Liu X, Han Y and Zeng H: Elevated intracranial pressure induces IL-1β and IL-18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats. Int J Mol Med. 47:183–194. 2021. View Article : Google Scholar : PubMed/NCBI

10 

Song L, Pei L, Yao S, Wu Y and Shang Y: NLRP3 inflammasome in neurological diseases, from functions to therapies. Front Cell Neurosci. 11:632017. View Article : Google Scholar : PubMed/NCBI

11 

Liao LZ, Chen ZC, Wang SS, Liu WB, Zhao CL and Zhuang XD: NLRP3 inflammasome activation contributes to the pathogenesis of cardiocytes aging. Aging (Albany NY). 13:20534–20551. 2021. View Article : Google Scholar : PubMed/NCBI

12 

Lian H, Fang X, Li Q, Liu S, Wei Q, Hua X, Li W, Liao C and Yuan X: NLRP3 inflammasome-mediated pyroptosis pathway contributes to the pathogenesis of Candida albicans keratitis. Front Med (Lausanne). 9:8451292022. View Article : Google Scholar : PubMed/NCBI

13 

Liu L, Wang N, Kalionis B, Xia S and He Q: HMGB1 plays an important role in pyroptosis induced blood brain barrier breakdown in diabetes-associated cognitive decline. J Neuroimmunol. 362:5777632022. View Article : Google Scholar : PubMed/NCBI

14 

Ismael S, Nasoohi S, Yoo A, Ahmed HA and Ishrat T: Tissue plasminogen activator promotes TXNIP-NLRP3 inflammasome activation after hyperglycemic stroke in mice. Mol Neurobiol. 57:2495–2508. 2020. View Article : Google Scholar : PubMed/NCBI

15 

Ardehali MR and Rondouin G: Microsurgical intraluminal middle cerebral artery occlusion model in rodents. Acta Neurol Scand. 107:267–275. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Percie du Sert N, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, et al: Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol. 18:e30004112020. View Article : Google Scholar : PubMed/NCBI

17 

Ding HG, Li Y, Li XS, Liu XQ, Wang KR, Wen MY, Jiang WQ and Zeng HK: Hypercapnia promotes microglial pyroptosis via inhibiting mitophagy in hypoxemic adult rats. CNS Neurosci Ther. 26:1134–1146. 2020. View Article : Google Scholar : PubMed/NCBI

18 

Desilles JP, Meseguer E, Labreuche J, Lapergue B, Sirimarco G, Gonzalez-Valcarcel J, Lavallée P, Cabrejo L, Guidoux C, Klein I, et al: Diabetes mellitus, admission glucose, and outcomes after stroke thrombolysis: A registry and systematic review. Stroke. 44:1915–1923. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Li J, Quan K and Wang Y, Zhao X, Li Z, Pan Y, Li H, Liu L and Wang Y: Effect of stress hyperglycemia on neurological deficit and mortality in the acute ischemic stroke people with and without diabetes. Front Neurol. 11:5768952020. View Article : Google Scholar : PubMed/NCBI

20 

Li WA, Moore-Langston S, Chakraborty T, Rafols JA, Conti AC and Ding Y: Hyperglycemia in stroke and possible treatments. Neurol Res. 35:479–491. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Yu P, Zhang X, Liu N, Tang L, Peng C and Chen X: Pyroptosis: Mechanisms and diseases. Signal Transduct Target Ther. 6:1282021. View Article : Google Scholar : PubMed/NCBI

22 

Qiu Z, Lei S, Zhao B, Wu Y, Su W, Liu M, Meng Q, Zhou B, Leng Y and Xia ZY: NLRP3 inflammasome activation-mediated pyroptosis aggravates myocardial ischemia/reperfusion injury in diabetic rats. Oxid Med Cell Longev. 2017:97432802017. View Article : Google Scholar : PubMed/NCBI

23 

Lin J, Cheng A, Cheng K, Deng Q, Zhang S, Lan Z, Wang W and Chen J: New insights into the mechanisms of pyroptosis and implications for diabetic kidney disease. Int J Mol Sci. 21:70572020. View Article : Google Scholar : PubMed/NCBI

24 

Zhao P, Yue Z, Nie L, Zhao Z and Wang Q, Chen J and Wang Q: Hyperglycaemia-associated macrophage pyroptosis accelerates periodontal inflamm-aging. J Clin Periodontol. 48:1379–1392. 2021. View Article : Google Scholar : PubMed/NCBI

25 

Cui Y, Chen XB, Liu Y, Wang Q, Tang J and Chen MJ: Piperlongu-mine inhibits esophageal squamous cell carcinoma in vitro and in vivo by triggering NRF2/ROS/TXNIP/NLRP3-dependent pyroptosis. Chem Biol Interact. 390:1108752024. View Article : Google Scholar : PubMed/NCBI

26 

Wang J, Yin Y, Zhang Q, Deng X, Miao Z and Xu S: HgCl2 exposure mediates pyroptosis of HD11 cells and promotes M1 polarization and the release of inflammatory factors through ROS/Nrf2/NLRP3. Ecotoxicol Environ Saf. 269:1157792024. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Luo E, Li Z, Zhang S, Wen Y, Yang Z, Zeng H and Ding H: Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke. Mol Med Rep 30: 146, 2024.
APA
Luo, E., Li, Z., Zhang, S., Wen, Y., Yang, Z., Zeng, H., & Ding, H. (2024). Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke. Molecular Medicine Reports, 30, 146. https://doi.org/10.3892/mmr.2024.13270
MLA
Luo, E., Li, Z., Zhang, S., Wen, Y., Yang, Z., Zeng, H., Ding, H."Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke". Molecular Medicine Reports 30.2 (2024): 146.
Chicago
Luo, E., Li, Z., Zhang, S., Wen, Y., Yang, Z., Zeng, H., Ding, H."Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke". Molecular Medicine Reports 30, no. 2 (2024): 146. https://doi.org/10.3892/mmr.2024.13270
Copy and paste a formatted citation
x
Spandidos Publications style
Luo E, Li Z, Zhang S, Wen Y, Yang Z, Zeng H and Ding H: Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke. Mol Med Rep 30: 146, 2024.
APA
Luo, E., Li, Z., Zhang, S., Wen, Y., Yang, Z., Zeng, H., & Ding, H. (2024). Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke. Molecular Medicine Reports, 30, 146. https://doi.org/10.3892/mmr.2024.13270
MLA
Luo, E., Li, Z., Zhang, S., Wen, Y., Yang, Z., Zeng, H., Ding, H."Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke". Molecular Medicine Reports 30.2 (2024): 146.
Chicago
Luo, E., Li, Z., Zhang, S., Wen, Y., Yang, Z., Zeng, H., Ding, H."Hyperglycemia induces microglial pyroptosis by increasing oxygen extraction rate: Implication in neurological impairment during ischemic stroke". Molecular Medicine Reports 30, no. 2 (2024): 146. https://doi.org/10.3892/mmr.2024.13270
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team