ACUTE INTESTINAL INFLAMMATION ALTERS CEREBRAL HEMODYNAMIC STABILITY AND FUNCTIONAL CONNECTIVITY IN MICE

Introduction: Inflammatory bowel disease (IBD) is associated with an increased risk of cerebrovascular events, likely driven by systemic inflammation. Using a dextran sulphate sodium (DSS)-induced colitis model, we investigated whether acute intestinal inflammation alters cerebral haemodynamics and functional connectivity using functional ultrasound imaging (fUS).

Methods: CD1 mice (n=40, 50% female) were administered 5% w/v DSS or standard drinking water for three days. Disease activity index (DAI) was assessed daily. Following exposure, resting-state fUS imaging (Iconeus One) was performed under isoflurane anaesthesia to map cerebral blood volume (CBV) and functional connectivity across 20 regions of interest (ROIs). Faecal calprotectin and serum inflammatory/coagulation markers (IL-6, VWF:Ag, VWF:CBA, and ADAMTS13) were quantified via ELISA. Group comparisons utilized t-tests with permutation-based family-wise error rate (FWER) control.

Results: DSS exposure induced significant intestinal and systemic inflammation, evidenced by elevated DAI scores, faecal calprotectin, and serum IL-6 levels. Coagulation-related markers did not differ significantly between groups. Resting-state fUS revealed a consistent but modest increase in mean ΔCBV in DSS-treated mice, though no single ROI survived FWER correction. Notably, the temporal association, auditory, and ectorhinal cortices exhibited significantly greater temporal variability of ΔCBV (p < 0.05), suggesting increased haemodynamic fluctuation. Furthermore, ROI-to-ROI analysis identified significantly increased functional connectivity between auditory and ectorhinal regions in the DSS group.

Conclusion: Acute intestinal inflammation correlates with altered cerebral haemodynamic fluctuations and reorganized functional connectivity, providing insight into the systemic reach of IBD-related pathology on brain function.