RIP1-RIP3-DRP1 pathway regulates NLRP3 inflammasome activation following subarachnoid hemorrhage.

In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection. SAH grade, neurological function, brain water content, Western blot, ROS assay, immunofluorescence and transmission electron microscopy were performed. SAH led to the upregulation of RIP1, RIP3, phosphorylated DRP1 and NLRP3 inflammasome. Nec-1 treatment reduced RIP1, RIP3, phosphorylated DRP1 and NLRP3 inflammasome, subsequently alleviated brain edema and neurological deficits at 24h following SAH. The treatment with Mdivi-1 inhibited the expression of DRP1 protein, attenuated mitochondria damage and the generation of ROS, inhibition NLRP3 inflammasome and ameliorated brain edema and neurological deficits at 24h after SAH. The activation of the NLRP3 inflammasome in EBI after SAH was mediated by RIP1-RIP3-DRP1 pathway. Nec-1 and Mdivi-1 can inhibit inflammation and improve neurological function after SAH.
PMID: 28579326 [PubMed - as supplied by publisher]

Source: Experimental Neurology - June 2, 2017 Category: Neurology Authors: Zhou K, Shi L, Wang Z, Zhou J, Manaenko A, Reis C, Chen S, Zhang J Tags: Exp Neurol Source Type: research