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Elevated intracranial pressure induces IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats

  • Authors:
    • Hongguang Ding
    • Ya Li
    • Miaoyun Wen
    • Xinqiang Liu
    • Yongli Han
    • Hongke Zeng
  • View Affiliations / Copyright

    Affiliations: Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China
    Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 183-194
    |
    Published online on: November 3, 2020
       https://doi.org/10.3892/ijmm.2020.4779
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Abstract

Elevated intracranial pressure (ICP) is one of the most common complications following an ischemic stroke, and has implications for the clinical and neurological outcomes. The aim of the present study was to examine whether elevated ICP may increase IL‑1β and IL‑18 secretion by activating the NOD‑like receptor protein 3 (NLRP3) inflammasome in microglia of ischemic adult rats. Sprague‑Dawley rats that underwent middle cerebral artery occlusion were used for assessment of ICP. Reactive oxygen species (ROS) production was detected, and western blotting and immunofluorescence staining were used to determine the expression levels of Caspase‑1, gasdermin D‑N domains (GSDMD‑N), IL‑1β and IL‑18 in microglial cells. ICP levels were significantly increased, which was accompanied by ROS overproduction, in the brain tissue following ischemia‑reperfusion (IR) injury in rats. Treatment with 10% hypertonic saline by intravenous injection significantly reduced the ICP and ROS levels of the rats. Furthermore, high pressure (20 mmHg) combined with oxygen‑glucose deprivation (OGD) treatment resulted in increased ROS production in BV‑2 microglial cells compared with those subjected to OGD treatment alone in vitro. Elevated pressure upregulated the expression of Caspase‑1, GSDMD‑N, IL‑18 and IL‑1β in IR‑treated or OGD‑treated microglia both in vivo and in vitro. More importantly, Caspase‑1, GSDMD‑N, IL‑18 and IL‑1β expression in microglia was significantly downregulated when elevated pressure was reduced or removed. These results suggested that elevated ICP‑induced IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome by ischemia‑activated microglia may augment neuroinflammation.
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Copy and paste a formatted citation
Spandidos Publications style
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.
APA
Ding, H., Li, Y., Wen, M., Liu, X., Han, Y., & Zeng, H. (2021). Elevated intracranial pressure induces IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats. International Journal of Molecular Medicine, 47, 183-194. https://doi.org/10.3892/ijmm.2020.4779
MLA
Ding, H., Li, Y., Wen, M., Liu, X., Han, Y., Zeng, H."Elevated intracranial pressure induces IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats". International Journal of Molecular Medicine 47.1 (2021): 183-194.
Chicago
Ding, H., Li, Y., Wen, M., Liu, X., Han, Y., Zeng, H."Elevated intracranial pressure induces IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats". International Journal of Molecular Medicine 47, no. 1 (2021): 183-194. https://doi.org/10.3892/ijmm.2020.4779
Copy and paste a formatted citation
x
Spandidos Publications style
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.
APA
Ding, H., Li, Y., Wen, M., Liu, X., Han, Y., & Zeng, H. (2021). Elevated intracranial pressure induces IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats. International Journal of Molecular Medicine, 47, 183-194. https://doi.org/10.3892/ijmm.2020.4779
MLA
Ding, H., Li, Y., Wen, M., Liu, X., Han, Y., Zeng, H."Elevated intracranial pressure induces IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats". International Journal of Molecular Medicine 47.1 (2021): 183-194.
Chicago
Ding, H., Li, Y., Wen, M., Liu, X., Han, Y., Zeng, H."Elevated intracranial pressure induces IL‑1β and IL‑18 overproduction via activation of the NLRP3 inflammasome in microglia of ischemic adult rats". International Journal of Molecular Medicine 47, no. 1 (2021): 183-194. https://doi.org/10.3892/ijmm.2020.4779
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