Intestinal Ischemia/Reperfusion Injury Influences Hyaluronan Homeostasis in the Rat Brain.

Area of Science:

• Neuroscience
• Gastroenterology
• Immunology

Background:

• Intestinal ischemia and reperfusion injury (IRI) can cause systemic organ dysfunction, including central nervous system (CNS) neuroinflammation.
• Hyaluronan, an extracellular matrix component, influences neuronal and immune functions during intestinal IRI.

Purpose of the Study:

• To investigate hyaluronan's role in CNS alterations following intestinal IRI in rats.
• To examine the impact of hyaluronan synthesis inhibition on neuroinflammation in the hippocampus and striatum.

Main Methods:

• Adult male rats underwent 60 min of mesenteric ischemia followed by 24 h reperfusion.
• Animals were treated with 4-methylumbelliferone (4-MU), a hyaluronan synthesis inhibitor.
• Levels of hyaluronan, neurocan, Has2, and inflammatory markers (IL6, TLR4-NFκB-pIκB pathway) were assessed in the hippocampus and striatum.

Main Results:

• Intestinal IRI downregulated hyaluronan, neurocan, and Has2 in the hippocampus and striatum.
• IRI altered the TLR4-NFκB-pIκB pathway, with greater effects in the hippocampus.
• Increased IL6 levels, co-localizing with microglia, were observed and partially reduced by 4-MU in the hippocampus.

Conclusions:

• Intestinal IRI disrupts CNS extracellular matrix homeostasis, promoting hyaluronan-mediated neuroinflammation.
• Hyaluronan signaling, particularly IL6 and microglial activation in the hippocampus, may contribute to cognitive deficits after intestinal IRI.
• Targeting hyaluronan synthesis presents a potential therapeutic strategy for CNS complications of intestinal IRI.