Hyaluronan: a new player in the modulation of adaptive changes to neuromuscular damage in the gastrointestinal tract

Pathological conditions of the gastrointestinal tract, such as chronic inflammatory states or intestinal ischemia/reperfusion (I/R) injury, have severe consequences on different cell types constituting the enteric microenvironment. In particular, myenteric neurons are especially sensitive, and can be irreversibly damaged, resulting in structural and functional changes of the enteric circuitries. Such changes may be, at least in part, due to the interplay among different cell populations of enteric microenvironment. Hyaluronan (HA) represents an important molecule of the extracellular matrix (ECM), which provides an significant framework for that microenvironment. In this context, the aim of my thesis was to evaluate possible changes of HA homeostasis in myenteric ganglia after an experimentally induced colitis and an in vivo-induced ischemia/reperfusion (I/R) damage in rats. Results showed that myenteric neurons synthesize HA to form a well-structured perineuronal net, which undergoes derangement when myenteric ganglia homeostasis is perturbed, i.e. during the inflammatory state in the experimentally-induced colitis. In addition, data indicated that in the neuromuscular compartment of the rat small intestine, an I/R injury increases HA levels, and that HA may influence both the excitatory and inhibitory components of the peristaltic reflex. Overall, this study provides evidence that HA deposition within myenteric ganglia may have a homeostatic role, contributing to the control of myenteric neuron structure and function and supporting the efficiency of the gastrointestinal transit. Hence, modulation of HA deposition within myenteric ganglia may ameliorate intestinal motility patterns related to these disease states.