FIGURE 3.

Working hypothesis of Glial Molecular Mechanisms Implicated in the Pathogenesis of POI. Under normal physiological conditions, glial cells modulate motility by interacting with neural-motor components of the gut. Glia communicate with each other and the ENS via Ca²⁺ waves and release of gliotransmitters. Recent evidence has revealed a number of potential glial targets implicated in the pathogenesis of POI and POGD. Gut surgical trauma and manipulation induces a reactive enteric glial phenotype that contributes to the overall neuroinflammation and GI dysmotility. Experimental evidence in reactive glia suggests that a variety of glial molecular signaling mechanisms may be operating in POI. These include 1) abnormal mechanosensation, 2) purinergic pathways via ATP, 3) the IL1β/IL1R Signaling Pathway, 4) the ET-1/ETBR signalling pathway, 5) the s100β-RAGE/iNOS/NO signaling pathway, and 6) a PPARα signaling pathway targeted by PEA to inhibit inflammation.