Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice

Objective To investigate the mechanism of SUMO-specific protease 1 (Senp1) involved in neuronal pyroptosis in subarachnoid hemorrhage (SAH). Methods A total of 95 male C57BL/6 mice (6~8 weeks old) were randomly divided into sham group (n=15), SAH groups (for 6, 12, 24, 48 and 72 h, respectively, n=8, 7, 17, 6 and 6), SAH+AAV9-NC group (n=19), and SAH+AAV9-sh-Senp1 group (n=17). Mouse model of SAH was established by intravascular puncture in the left internal carotid artery. Neurobehavioral scoring was used to evaluate neurological function, HE staining and FJC staining were employed to observe brain injury, RT-PCR was conducted to detect the knockdown of Senp1, Western blotting was applied to measure the expression of Senp1, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), gasdermin D (GSDMD), PYD and CARD domain containing (ASC) and Caspase-1, and immunofluorescence assay was performed to observe the locations of Senp1 and NLRP3. Results SAH caused the elevated expression of Senp1, which reached a peak in 24 h and located in the cortical neurons. Compared with the sham group, the expression of Senp1, NLRP3, GSDMD, ASC and Caspase-1 were significantly enhanced in the SAH groups (P < 0.01), with aggravation of nerve injury and neurological deficits. Administration of AAV9-sh-Senp1 resulted in significantly improved nerve injury and function, decreased expression of above proteins (P < 0.01), and inhibited neuron pyroptosis when compared with the SAH+AAV9-NC group. Conclusion Senp1 promotes the occurrence of neuronal pyroptosis and mediates neuronal injury after SAH.