NLRP3 inflammasome-mediated cerebrospinal fluid hypersecretion in choroid plexus contributes to hydrocephalus after hemorrhage

Abstract BackgroundHydrocephalus is a severe complication of intracerebral hemorrhage with ventricular extension (ICH-IVH). The choroid plexus epithelium plays an important role in cerebrospinal fluid (CSF) secretion and constitutes blood-CSF barrier adjusting brain–immune system interface. NLRP3 inflammasome is a key component of the innate system which promotes neuroinflammation. However, the role of NLRP3 inflammasome in the pathogenesis of hydrocephalus after hemorrhage has not been investigated.MethodsHydrocephalus after ICH-IVH rat model was accomplished by autologous blood infusion. Then, we investigated the relationship between NLRP3 inflammasome and CSF hypersecretion in choroid plexus.ResultsThe NLRP3 inflammasome activated and CSF hypersecretion in choroid plexus epithelium were found after ICH-IVH. NLRP3 inhibition with MCC950 decreased CSF secretion, ventricles dilation and attenuated neurofunction deficits after ICH-IVH. In addition, MCC950 decreased NKCC1 phosphorylation which was the major protein adjusting CSF secretion and improved blood-CSF barrier integrity after ICH-IVH.ConclusionsThis study demonstrates that NLRP3 inflammasome mediated CSF hypersecretion by influencing NKCC1 phosphorylation in choroid plexus epithelium plays an important role in the pathogenesis of hydrocephalus after hemorrhage and provides a new therapeutic strategy.