Sympathetic-Mediated Intestinal Cell Death Contributes to Gut Barrier Impairment After Stroke
Kathryn Prame Kumar1, Liam D McKay1, Huynh Nguyen1
1Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences at Monash Health, Monash Medical Centre, Monash University, Clayton, VIC, 3168, Australia.
Translational Stroke Research
|November 29, 2023
Summary
Stroke causes gut permeability by increasing intestinal cell death, mediated by the sympathetic nervous system. The gut adapts with gene changes and cell hyperplasia, but denervation restores normal function.
Area of Science:
- Neuroscience
- Gastroenterology
- Pathophysiology
Background:
- Stroke is traditionally viewed as a localized brain injury.
- Emerging evidence links stroke to systemic effects, including gastrointestinal dysfunction.
Purpose of the Study:
- To investigate the mechanisms of gut permeability following stroke.
- To understand the brain-gut axis in post-stroke pathophysiology.
Main Methods:
- Utilized a permanent intraluminal middle cerebral artery occlusion (pMCAO) model in mice.
- Assessed gut permeability, intestinal epithelial cell death, gene expression, and crypt/goblet cell morphology.
- Employed pharmacological denervation to investigate sympathetic nervous system involvement.
Main Results:
- Stroke induced gut permeability and increased intestinal epithelial cell death at 5 hours post-pMCAO.
- At 24 hours, the gut barrier integrity was restored, with evidence of compensatory hyperplasia and altered fructose metabolism gene expression.
- Pharmacological denervation normalized stroke-induced gut changes, indicating sympathetic nervous system mediation.
Conclusions:
- Stroke triggers intestinal cell death and gut permeability via sympathetic nervous system activation.
- The brain-gut axis plays a critical role in systemic complications following stroke.
- The gut exhibits compensatory mechanisms in response to stroke-induced barrier impairment.
