Roles of programmed death protein 1/programmed death-ligand 1 in secondary brain injury after intracerebral hemorrhage in rats: Selective modulation of microglia polarization to anti-inflammatory phenotype

Background: microglia and its polarization play critical roles in intracerebral hemorrhage-induced secondary brain injury. programmed death protein 1/programmed death-ligand 1 has been reported to regulate neuroimmune cell functions. signal transducers and activators of transcription 1 participate in microglia polarization,and programmed death protein 1/programmed death-ligand 1 could regulate the activation of signal transducers and activators of transcription 1. we herein show the critical role of programmed death protein 1/programmed death-ligand 1 in the polarization of microglia during intracerebral hemorrhage-induced secondary brain injury in rat models. methods: an autologous blood intracerebral hemorrhage model was established in sprague dawley rats (weighing 250-300 g),and primary cultured microglia was exposed to oxyhemoglobin to mimic intracerebral hemorrhage in vitro. specific sirnas and pdna for programmed death protein 1 and programmed death-ligand 1 were exploited both in vivo and in vitro. results: in the brain tissue around hematoma,the protein levels of programmed death protein 1 and programmed death-ligand 1 and the interaction between them,as well as the phosphorylation of signal transducers and activators of transcription 1,were higher than that of the sham group and collectively peaked at 24 h after intracerebral hemorrhage. overexpression of programmed death protein 1 and programmed death-ligand 1 ameliorated intracerebral hemorrhage-induced secondary brain injury,including brain cell death,neuronal degeneration,and inflammation,while their knockdown induced an opposite effect. in addition,overexpression of programmed death protein 1 and programmed death-ligand 1 selectively promoted microglia polarization to anti-inflammation phenotype after intracerebral hemorrhage and inhibited the phosphorylation of signal transducers and activators of transcription 1,suggesting that intracerebral hemorrhage-induced increases in programmed death protein 1 and programmed death-ligand 1 maybe a self-help. conclusions: enhancing the expressions of programmed death protein 1 and programmed death-ligand 1 may induce a selective modulation of microglia polarization to anti-inflammation phenotype for intracerebral hemorrhage treatment. © 2017 the author(s).