Regional Heterogeneity in Intestinal Epithelial Barrier Permeability and Mesenteric Perfusion After Thoracic Spinal...

Area of Science:

• Neuroscience
• Gastroenterology
• Physiology

Background:

• Spinal cord injury (SCI) impairs intestinal barrier function, increasing antigen absorption and negatively impacting patient outcomes.
• Existing research often overlooks the anatomical and physiological diversity of the intestines, failing to address regional differences in pathophysiology post-SCI.

Purpose of the Study:

• To investigate the regional impact of high thoracic SCI on intestinal barrier function.
• To assess oxidative stress, paracellular permeability, tight junction protein expression, and hindgut perfusion in a rodent model.

Main Methods:

• High thoracic spinal cord injury (SCI) induction in a rodent model.
• Regional assessment of mucosal oxidative stress (dihydroethidium labeling).
• Ussing chamber analysis of paracellular permeability using small and large molecular probes.
• Quantification of intestinal tight junction (TJ) protein expression (claudin-2, occludin).
• Measurement of hindgut perfusion via caudal mesenteric artery flow.

Main Results:

• SCI elevated duodenal mucosal oxidative stress and permeability (urea, inulin flux) at 3 days post-injury.
• Increased claudin-2 expression and decreased occludin expression were observed in the duodenum and proximal colon.
• Claudin-2 remained elevated in the proximal colon at 3 weeks post-SCI.
• Hindgut perfusion and barrier function remained unchanged despite systemic hypotension.

Conclusions:

• High thoracic SCI induces regional intestinal pathophysiology, primarily affecting the proximal intestine.
• Oxidative stress, altered tight junction protein expression, and increased barrier permeability characterize proximal intestinal dysfunction post-SCI.
• The hindgut demonstrates resilience to SCI-induced barrier disruption, suggesting regional heterogeneity in response.