USP18 Overexpression Protects against Focal Cerebral Ischemia Injury in Mice by Suppressing Microglial Activation

This study aims to determine whether USP18 expression protects against brain damage in ischemic models of stroke. We investigated USP18 expression, overexpression, and knockout under ischemic conditions in vitro and in vivo. Using BV2 microglial cells under oxygen and glucose deprivation (OGD) and 60 min transient middle cerebral artery occlusion (MCAO) in mice as models of ischemia, we assessed the infarct volume, the extent of neurogenesis, the expression of proinflammatory cytokines and Janus Kinases (JAKs)/Signal Transducer and Activator of Transcription (STAT) pathway members. BV2 cells under OGD for 0, 6, 12, or 24 hours exhibited decreased USP18 expression and increased expression of the proinflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and interferon (INF)-γ. Lentiviral overexpression of USP18 in MCAO mice significantly decreased the infarct volume and significantly increased the number of new neurons that coexpressed bromodeoxyuridine (BrdU)/ neuronal nuclei (NeuN). Additionally, microglial activation was inhibited, including the suppression of the JAK/STAT pathway and the proinflammatory cytokines expression. In vitro experiments demonstrated that USP18 inhibited BV2 microglial activity and reduced the mRNA and protein levels of NF-κB, JAK1, p-JAK1, STAT1, and p-STAT1 in BV2 microglial cells. USP18 overexpression decreased ischemic brain injury through the suppression of microglial activation by negatively regula...
Source: Neuroscience - Category: Neuroscience Source Type: research