AOM-induced HE is associated with increased blood-brain barrier permeability and an increase of MMP-9 expression and we have previously demonstrated that certain bile acids can increase the permeability of the blood brain barrier (Quinn et al., 2014) indicating that bile acid-mediated S1PR2 signaling could conceivably influence this aspect of pathology during HE (Chastre et al., 2014; McMillin M. A. et al., 2015). This evidence concerns the gene MMP9 and hereditary elliptocytosis.