EPO and brain edema: For example, study showed that the overexpressions of AQP4 were involved in the development of CO poisoning-induced cerebral oedema through p38 MAPK signaling in rat astrocytes [47], while another study showed that Erythropoietin (EPO) protects BBB from disruption after ICH is associated with increased levels of AQP4 through activation of p38 MAPK pathways after binding to EPOR [43].