A novel RIP1/RIP3 dual inhibitor promoted OPC survival and myelination in a rat neonatal white matter injury model with hOPC graft

Abstract Background The dual inhibitors of receptor interacting protein kinase-1 and -3 (RIP1 RIP3) play an important role in cell death processes inflammatory responses. White matter injury (WMI), a leading cause neurodevelopmental disabilities preterm infants, which is characterized by extensive myelination disturbances demyelination. Neuroinflammation, leads to the loss differentiation-inhibition oligodendrocyte precursor cells (OPCs), represents major barrier myelin repair. Whether novel RIP1/RIP3 inhibitor ZJU-37 can promote transplanted OPCs derived from human neural stem (hOPCs) survival, differentiation remains unclear. In this study, we investigated effect on neurobehavioral function neonatal rat WMI model induced hypoxia ischemia. Methods vivo, P3 pups were subjected right common carotid artery ligation hypoxia, then treated with or/and hOPCs, apoptosis, myelination, glial NLRP3 inflammasome activation together cognitive outcome evaluated at 12 weeks after transplantation. vitro, astrocytes oxygen–glucose deprivation (OGD) examined western blot immunofluorescence. apoptosis conditioned medium OGD-injured (OGD-astrocyte-CM) was analyzed flow cytometry Results combined hOPCs more effectively decreased OPC promoted corpus callosum improved behavioral compared or treatment. addition, reduced treatment model. it also confirmed that suppress OGD. Not only that, OGD-astrocyte-CM obviously attenuated dysdifferentiation caused OGD-astrocyte-CM. Conclusions may inhibiting hOPC graft.