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Hydrogen sulphide protects mice against the mutual aggravation of cerebral ischaemia/reperfusion injury and colitis.

Abstract
This study was undertaken to determine whether ischaemia/reperfusion (I/R)-induced brain injury and dextran sulfate sodium (DSS)-induced colitis in mice are related. A cerebral I/R model of mice was established by blocking the bilateral common carotid arteries; 3% DSS in drinking water was administered to mice for 7 days to induce colitis; mice with cerebral I/R and colitis were administered DSS for 7 days from the third day onwards after acute cerebral I/R. Brain damage and intestinal inflammation were also tested. The results revealed that cerebral I/R induced brain damage and a marked increase in glial fibrillary acidic protein (GFAP) expression and upregulation of Rho-associated coiled coil-forming protein kinase (RhoA/ROCK) pathway in mouse hippocampal tissues. However, in the colon tissues of mice with colitis, we found a reduction in GFAP. In addition, the expression of endogenous hydrogen sulphide (H2S) synthase reduced in mice brain tissues with cerebral I/R injury, as well. as in mouse colon tissues with colitis. Interestingly, the cerebral I/R-induced pathological changes in mouse brain tissues were aggravated by colitis, colitis mediated colon inflammation, and pathological changes in intestinal tissues had deteriorated when the mice suffered cerebral I/R 2 days before DSS administration. However, brain injury and colon inflammation in mice suffering from both cerebral I/R and colitis were ameliorated by NaHS, an exogenous H2S donor. Furthermore, we found that NaHS promoted the transformation of astrocytes from "A1" to "A2" type. These findings reveal that cerebral I/R injury and colitis are related, the mechanism is correlated with endogenous H2S deficiency.
AuthorsYanyu Ding, Bo Liu, Yang Zhang, Fang Fang, Xueyan Li, Song Wang, Jiyue Wen
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 914 Pg. 174682 (Jan 05 2022) ISSN: 1879-0712 [Electronic] Netherlands
PMID34871558 (Publication Type: Journal Article)
CopyrightCopyright © 2021 Elsevier B.V. All rights reserved.
Chemical References
  • Glial Fibrillary Acidic Protein
  • Protective Agents
  • Sulfides
  • glial fibrillary astrocytic protein, mouse
  • Dextran Sulfate
  • rho-Associated Kinases
  • sodium bisulfide
Topics
  • Animals
  • Brain Ischemia (drug therapy, immunology, metabolism)
  • Brain-Gut Axis (drug effects, physiology)
  • Colitis (drug therapy, immunology)
  • Dextran Sulfate (pharmacology)
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein (metabolism)
  • Mice
  • Protective Agents (pharmacology)
  • Reperfusion Injury (drug therapy, metabolism)
  • Signal Transduction (drug effects)
  • Sulfides (pharmacology)
  • Treatment Outcome
  • Up-Regulation
  • rho-Associated Kinases (metabolism)

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