FIGURE 4.

Overview of pyroptosis pathways following ICH. Nucleotide-binding oligomerization domain-like receptors (NLRs) can be activated by the degradation products of erythrocytes (such as hemoglobin, heme, and iron) and activated purinergic receptors via ROS, leading to the formation of inflammasome. Then, NLR pyrin domain-containing 3 (NLRP3) and NLRP1 inflammasome activate caspase to initiate the cleavage and activation of interleukin-1β (IL-1β) and interleukin-18 (IL-18). Moreover, active caspase can also cleave gasdermin to form gasdermin D-N fragment, which causes non-selective pores in membrane, inducing the release of mature IL-1β and IL-18 to elicit neuroinflammation and cell death after ICH.