Accumulating evidence indicates that post-injury inflammation characterized by activated microglia contributes much to the neuropathology of ischemic injury. Several studies have demonstrated that microglia exhibit two entirely different functional activation states, referred to as classically activated (M1) and alternatively activated (M2) phenotype. Promoting microglial phenotype to switch from M1 dominant to M2 dominant might be a promising approach for handling ischemic injury. However, the comprehensive mechanism that underlines microglia polarization in ischemic brain remains unclear. Neuronal erythropoietin-producing human hepatocellular carcinoma cell receptor 4 (EphA4), the richest Eph receptor in the central nervous system (CNS), upregulate after ischemia and may have the potential to regulate microglia activation. We hypothesized that modulating EphA4/ephrin signaling could affect ischemic injury through controlling microglia polarization. We therefore knocked down neuronal EphA4 with short hairpin RNA (shRNA) and determined the role of EphA4/ephrin signaling in oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury. We found that EphA4 shRNA treatment attenuated OGD/R-induced apoptosis and microglia proliferation. Neuronal EphA4 knockdown also promoted microglial M2 polarization, which reduced pro-inflammatory mediators and released anti-inflammatory cytokines as well as neurotrophic factors. We further revealed that EphA4 shRNA treatment functioned through RhoA/Rho-associated kinase 2 (ROCK2) signaling, a key mediator of microglia alternative activation. Together, these data suggested that blockage of EphA4/ephrin signaling between neuron and microglia decreased OGD/R-induced injury by promoting alternative activation of microglia via RhoA/ROCK2 signaling.
Pubmed ID: 30361852 RIS Download
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This polyclonal targets Iba1
View all literature mentionsThis monoclonal targets MAP2 (phospho S136) antibody [EPR2361]
View all literature mentionsThis polyclonal targets Eph receptor A4
View all literature mentionsThis monoclonal targets ROCK2 antibody [EPR7141(B)]
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis monoclonal targets Rabbit n/a
View all literature mentionsThis polyclonal targets RhoA antibody
View all literature mentionsThis polyclonal targets Chitinase 3 like protein 3 antibody
View all literature mentionsThis polyclonal targets iNOS antibody
View all literature mentionsThis monoclonal targets PCNA antibody [EPR3821]
View all literature mentionsThis polyclonal targets beta Tubulin
View all literature mentionsThis polyclonal targets Glyceraldehyde-3-phosphate dehydrogenase
View all literature mentionsThis monoclonal targets ROCK2 antibody [EPR7141(B)]
View all literature mentionsThis polyclonal targets Eph receptor A4
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis monoclonal targets MAP2 (phospho S136) antibody [EPR2361]
View all literature mentions