Phthalide derivative CD21 ameliorates ischemic brain injury in a mouse model of global cerebral ischemia: involvement of inhibition of NLRP3.

In this study, we established a global cerebral ischemia-reperfusion model in mice by bilateral common carotid artery ligation (2VO), and explored the neuroprotective effect of CD21 and its anti-inflammatory mechanism on cerebral ischemia mice. CD21 significantly improved weight loss, neurobehavioral deficits and neurons loss in hippocampal CA1 and caudate putamen (CPu) subregions, which were induced by 2VO in mice. CD21 significantly inhibited the overactivation of astrocyte and microglia, and decreased the mRNA level of IL-6, TNF-α and IL-1β. Moreover, CD21 significantly inhibited the activation of TLR4/NF-κB signaling pathway mediated by HMGB1 and NLRP3/ASC/Caspase-1 signaling pathway mediated by Cathepsin B, thus inhibiting the activation of NLRP3 inflammasome. Our results demonstrated that CD21 may exert a neuroprotection by inhibiting NLRP3 inflammasome activation after cerebral ischemia. These findings provide a new strategy for the treatment of ischemic stroke. PMID: 32593156 [PubMed - as supplied by publisher]
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research