Sympathetic-Mediated Intestinal Cell Death Contributes to Gut Barrier Impairment After Stroke

Kathryn Prame Kumar, Liam D. McKay, Huynh Nguyen, Jasveena Kaur, Jenny L. Wilson, Althea R. Suthya, Sonja J. McKeown, Helen E. Abud, Connie H.Y. Wong

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Tissue injury induced by stroke is traditionally thought to be localised to the brain. However, there is an accumulating body of evidence to demonstrate that stroke promotes pathophysiological consequences in peripheral tissues including the gastrointestinal system. In this study, we investigated the mechanisms underlying gut permeability after stroke. We utilised the clinically relevant experimental model of stroke called permanent intraluminal middle cerebral artery occlusion (pMCAO) to examine the effect of cerebral ischaemia on the gut. We detected stroke-induced gut permeability at 5 h after pMCAO. At this timepoint, we observed significantly elevated intestinal epithelial cell death in post-stroke mice compared to their sham-operated counterparts. At 24 h after stroke onset when the gut barrier integrity is restored, our findings indicated that post-stroke intestinal epithelium had higher expression of genes associated with fructose metabolism, and hyperplasia of intestinal crypts and goblet cells, conceivably as a host compensatory mechanism to adapt to the impaired gut barrier. Furthermore, we discovered that stroke-induced gut permeability was mediated by the activation of the sympathetic nervous system as pharmacological denervation decreased the stroke-induced intestinal epithelial cell death, goblet cell and crypt hyperplasia, and gut permeability to baseline levels. Our study identifies a previously unknown mechanism in the brain-gut axis by which stroke triggers intestinal cell death and gut permeability.

Original languageEnglish
Number of pages19
JournalTranslational Stroke Research
DOIs
Publication statusAccepted/In press - 2023

Keywords

  • Barrier integrity
  • Brain-gut axis
  • Cerebral ischaemia
  • Epithelium
  • Gut permeability

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