F2R and brain edema: It has been established that activation of PAR-1 is most likely caused by thrombin, and the expression of PAR-1 and PAR-4 was significantly upregulated, which may mediate a series of thrombin reactions, leading to the neurocytotoxic damage and death (Wan et al., 2016), In addition, thrombin may also affect aquaporin 4 function via PAR-1 mediated aggravation of the cerebral edema after ICH (Wu et al., 2010; Gao et al., 2015).